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CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

A version of this article originally appeared on Medscape.com.

CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

A version of this article originally appeared on Medscape.com.

CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.

Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.

A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.

In the randomized controlled RESTORE study, use of the cell phone–based CBSM app was associated with significantly greater reduction in symptoms of anxiety and depression compared with a digital health education control app.

In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).

However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.

The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.

“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.

“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
 

Impressive and elegant

“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.

“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.

CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.

To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.

Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.

They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
 

High-quality control

Ms. Ramiller said that the control app set “a high bar.”

“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.

A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.

The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).

CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)

An extension study of the durability of the effects at 3 and 6 months is underway.

The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.

“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”

The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
 

A version of this article originally appeared on Medscape.com.

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

A version of this article first appeared on Medscape.com.

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

A version of this article first appeared on Medscape.com.

CHICAGO – Fewer than 7% of patients newly diagnosed with cancer are tested for germline genetic mutations, and the percentage tested was even lower among racial and ethnic minorities, a huge study has found.

Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.

The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.

The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.

“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.

“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”

Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.

The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.

“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.

They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.

“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.

At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.

The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.

Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.

“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.

One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.

“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.

Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
 

Details of the study

Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.

It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.

She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”

However, “little is known about genetic testing use and results,” Dr. Kurian noted.

The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.

The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.

The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.

Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.

Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.

Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.

Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.

The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.

By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.

The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.

Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.

There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.

However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.

The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).

With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).

Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.

She also noted that the SEER registries do not collect data on family history or tumor sequencing.

The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

A version of this article first appeared on Medscape.com.

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

A version of this article first appeared on Medscape.com.

Oncology fellows who completed diversity, equity, and inclusion (DEI) training report that they feel more confident about responding to different types of discrimination, both when directed at them personally and when directed at others.

The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).

Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.

“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”

Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.

The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).

At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.

First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.

Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.

Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.

“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”

Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.

The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.

The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.

Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.

Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.

“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”

No funding for the study was reported.

A version of this article first appeared on Medscape.com.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.

Seven months later, doctors and their patients are facing the unimaginable: In California, Virginia, and everywhere in between, they are being forced into grim contemplation of untested rationing plans for breast, cervical, bladder, ovarian, lung, testicular, and other cancers. Their decisions are likely to result in preventable deaths.

Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.

The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.

But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?

“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”

“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.

“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”

The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.

Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.

“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”

Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.

At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.

On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.

She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”

Doses remained at 80%, she said. Things hadn’t changed 10 days later.
 

Generics manufacturers are pulling out

The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.

As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.

The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.

Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.

The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.

Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.

Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”

Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.

“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
 

Should government step in?

Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.

As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.

Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”

More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.

“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.

Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.

In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.

“It would almost literally be a drop in the bucket.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.

The Food and Drug Administration has granted accelerated approval for glofitamab (Columvi) for use in certain types of lymphoma.

The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.

The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.

These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.

Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.

“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.

Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
 

Most common form of non-Hodgkin’s lymphoma

DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.

Glofitamab was given to all patients as a fixed course for 8.5 months.

More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.

The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).

Results from the NP30179 trial were published in December 2022.

The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”

The Food and Drug Administration has granted accelerated approval for glofitamab (Columvi) for use in certain types of lymphoma.

The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.

The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.

These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.

Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.

“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.

Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
 

Most common form of non-Hodgkin’s lymphoma

DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.

Glofitamab was given to all patients as a fixed course for 8.5 months.

More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.

The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).

Results from the NP30179 trial were published in December 2022.

The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”

The Food and Drug Administration has granted accelerated approval for glofitamab (Columvi) for use in certain types of lymphoma.

The indication is for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or with LBCL arising from follicular lymphoma who have received two or more lines of systemic therapy.

The product is a T cell–engaging bispecific antibody developed by Genentech, which has a similar product, mosunetuzumab-axgb (Lunsumio), for the treatment of follicular lymphoma. Lunsumio was approved in December 2022.

These drugs could be considered a first choice in the setting of third-line therapy, suggests an expert writing recently in The New England Journal of Medicine.

Nancy Bartlett, MD, from the Siteman Cancer Center, Washington University in St. Louis, is the author of an editorial that accompanied the publication of results with glofitamab in the pivotal trial that led to its approval.

“Bispecific agents will be an excellent option for the 60% of patients in whom second-line CAR [chimeric antigen receptor] T-cell therapy fails,” she wrote in her editorial.

Dr. Bartlett suggests that these agents may be preferred over CAR T cells. “If longer follow-up confirms that the majority of complete remissions with bispecific agents are durable, on the basis of the advantages of availability (including in the community setting) and more favorable immediate and late toxic-effect profiles, bispecific agents could be considered as the initial choice. ... CAR T-cell therapy could be held in reserve for patients who do not have a complete response or who have a relapse after a complete response.”
 

Most common form of non-Hodgkin’s lymphoma

DLBCL is the most common form of non-Hodgkin’s lymphoma in the United States, the company noted in a press release. While many people with DLBCL are responsive to treatment, the majority of those who experience relapse or whose condition is refractory to subsequent treatments have poor outcomes.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” commented Krish Patel, MD, director of the lymphoma program at the Swedish Cancer Institute in Seattle, who is an investigator on the clinical trial that led to the product’s approval. He said that the results from trials suggest that glofitamab gives patients “a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

The accelerated approval is based on response rate and durability of response results from the phase 1/2 NP30179 study.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This trial involved 132 patients with DLBCL who experienced relapse or whose condition was refractory to prior therapies. About one-third of patients (30%) had received prior CAR T-cell therapy. Additionally, for 83% of patients, the condition was refractory to their most recent therapy.

Glofitamab was given to all patients as a fixed course for 8.5 months.

More than half (56%) achieved an overall response, and 43% achieved a complete response. Over two-thirds (68.5%) of those who responded continued to respond for at least 9 months The median duration of response was 1.5 years.

The most common adverse events were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening; musculoskeletal pain (21%); fatigue (20%); and rash (20%). CRS was generally of low grade (52% of patients experienced grade 1 CRS, and 14% experienced grade 2).

Results from the NP30179 trial were published in December 2022.

The complete response rates seen with glofitamab rivals the durable complete response that has been observed with CAR T-cell therapy, Dr. Bartlett noted in the accompanying editorial. “Although these results are promising, it is still too early to estimate the curative potential of glofitamab.”

CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.

“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.

This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”

This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.

“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.

Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.

The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients. 

The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.

Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.

In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”

She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).

“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.

At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.

“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.

Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.

In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.

In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.

Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”

Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.

“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”

Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.

“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.

“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said. 

She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.

Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.

“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”

Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.

The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.

“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”

Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.

Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.

On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.

In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.

As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.

However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.

“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.

In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”

Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.

“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.

CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.

“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.

This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”

This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.

“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.

Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.

The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients. 

The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.

Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.

In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”

She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).

“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.

At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.

“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.

Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.

In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.

In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.

Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”

Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.

“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”

Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.

“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.

“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said. 

She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.

Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.

“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”

Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.

The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.

“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”

Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.

Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.

On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.

In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.

As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.

However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.

“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.

In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”

Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.

“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.

CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.

“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.

This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”

This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.

“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.

Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.

The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients. 

The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.

Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.

In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”

She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).

“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.

At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.

“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.

Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.

In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.

In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.

Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”

Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.

“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”

Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.

“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.

“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said. 

She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.

Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.

“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”

Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.

The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.

“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”

Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.

Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.

On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.

In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.

As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.

However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.

“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.

In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”

Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.

“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

CHICAGO – For the chief patient officer of the American Cancer Society, this year’s annual meeting of the American Society of Clinical Oncology was a gem. And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.

Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.

Below are lightly edited excerpts from a conversation with Dr. Kamal:



Question: What are some of most groundbreaking studies released at ASCO?

Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.

For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).



Q: How do these findings add to current knowledge?

A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.

Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.



Q: What else struck you as especially important research?

A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.

This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.

Even in these smaller, early tumors, osimertinib makes a difference.



Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?

A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.

If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.

That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.



Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?

A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.



Q: How can AI be helpful to medical providers considering its limitations?

A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.



Q: Will AI threaten the careers of oncologists?

A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.

Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.

Dr. Kamal has no disclosures.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

For patients with primary mediastinal B-cell lymphoma (PMBCL) who achieved a complete metabolic response after immunochemotherapy, radiation therapy may be safely omitted without heightening their risks of relapse or disease progression – thereby sparing them the toxicity and costs of this additional treatment.

“This study is the largest prospective study of PMBCL ever conducted,” said first author Emanuele Zucca, MD, consultant and head of the lymphoma unit at the Oncology Institute of Southern Switzerland in Bellinzona. Dr. Zucca presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

The results of the research underscore that “mediastinal radiation therapy in patients with complete remission after frontline immunochemotherapy can be safely omitted,” he said.

While PMBCL has a relatively low incidence, representing fewer than 5% of cases of non-Hodgkin lymphoma, the cancer is over-represented in young White women between approximately 30 and 40 years of age, and is a notably aggressive form of diffuse large B-cell lymphoma.

However, in patients who rapidly achieve remission with dose-intensive immunochemotherapy, the prognosis is good.

In such cases, the use of mediastinal radiation therapy has been seen as a measure to further consolidate the immunochemotherapy response, but the additional treatment comes at the cost of an increased risk of second malignancies, as well as coronary or valvular heart disease.

Meanwhile, in recent decades promising data has shown that aggressive chemoimmunotherapy regimens alone, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) can be enough for patients achieving a complete remission, while novel approaches such as checkpoint inhibitors and CAR T-cell therapy further show benefits in patients with lymphoma that relapses after treatment.

With ongoing controversy over whether to include the added radiation therapy among patients with a complete metabolic response, Dr. Zucca and his colleagues conducted the IELSG37 international study, enrolling 545 patients from 74 centers in 13 countries, including 336 women, with newly diagnosed PMBCL.

The patients were treated with induction chemoimmunotherapy with rituximab and anthracycline-based therapy based on local practice, and response assessed among of 530 of the 545 patients showed that 268 (50.6%) achieved a complete metabolic response.

Those patients were then randomized to either observation (n = 132) or consolidation radiation therapy (30 Gy; n = 136). The characteristics between the two groups were similar, with a mean age of 35.5, and about 65% female.

With a median follow-up of 63 months (range, 48-60 months), the primary endpoint of progression-free survival at 30 months was not significantly different between the observation arm (98.5%) and radiation therapy arm (96.2%; P = .278).

After adjustment for factors including sex, chemotherapy, country, and positron emission tomography (PET) response score, the estimated relative effect of radiotherapy versus observation was a hazard ratio of 0.68, and the absolute risk reduction associated with radiotherapy at 30 months was 1.2% after adjustment.

The number needed to treat is high, at 126.3 after stratification, and the 5-year overall survival was excellent in both arms, at 99%.

“What this tells us is that treatment with radiation therapy in well over 100 patients is needed just to avoid a single recurrence,” Dr. Zucca explained.

Overall survival after 3 years was excellent and identical in both arms, at about 99%.

To date, three severe cardiac events and three second cancers have been recorded in the study, all occurring among patients randomized to receive radiation therapy.

Dr. Zucca noted that longer follow-up is needed to better examine late toxicities.

“The long-term toxicities of mediastinal radiotherapy are well documented, particularly second breast, thyroid, and lung cancers and increased risk of coronary or valvular heart disease, in a patient group dominated by young adults,” Dr. Zucca said in a press statement.

“This study shows chemoimmunotherapy alone is an effective treatment for primary mediastinal B-cell lymphoma and strongly supports omitting radiotherapy without impacting chances of cure.”

Commenting on the study, Corey W. Speers, MD, PhD, assistant professor, radiation oncology, department of surgery, University of Michigan Hospital, Ann Arbor, said the findings have important clinical implications.

“We all should be encouraged by the low rates in this trial, which are lower than expected,” Dr. Speers said in a press briefing.

In further comments, he added that “these results will inform and likely change clinical practice.”

Dr. Speers said the study is notable for being the first of its kind.

“This clinical question has not previously been directly addressed, and this is the first study to do so,” he said.

“With more effective systemic therapies, many patients have their lymphoma disappear with early aggressive treatment, and although radiation is very effective at treating lymphoma, it has not been clear if it is needed in these patients that have an early rapid response to systemic therapy before starting radiation,” Dr. Speers explained.

“We have struggled as oncologists to know whether omitting this effective radiotherapy would compromise outcomes, and thus many were inclined to continue offering it to patients, even with the great early response. This study helps answer this critical question,” he said.

The results add reassuring evidence, buttressing efforts to avoid unnecessary interventions that may provide little or no benefit, Dr. Speers added.

“We are now in an era of ‘less being more’ as we seek ways to provide optimal quality and quantity of life to patients with cancer and their families, and this is just another example of the tremendous progress being made.”

Further commenting on the study at the press briefing, Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said the research supports ASCO’s ongoing efforts to reduce the toxicities of cancer treatment.

“Our ASCO vision is a world where cancer is either prevented or cured, and every patient is cured – and every survivor is healthy, and that part about every survivor being healthy is what we’re working on here [in this study],” Dr. Gralow said.

The study was funded by the Swiss Cancer League and Cancer Research UK, with partial support from the Swiss National Science Foundation. Dr. Zucca reported relationships with AstraZeneca, Beigene, Celgene, Incyte, Janssen, Merck, Roche, Celltrion Healthcare, Kite, and Abbvie. Dr. Speers disclosed his coinvention of technology that assesses radiosensitivity and predicts benefits from adjutant radiotherapy.

For patients with primary mediastinal B-cell lymphoma (PMBCL) who achieved a complete metabolic response after immunochemotherapy, radiation therapy may be safely omitted without heightening their risks of relapse or disease progression – thereby sparing them the toxicity and costs of this additional treatment.

“This study is the largest prospective study of PMBCL ever conducted,” said first author Emanuele Zucca, MD, consultant and head of the lymphoma unit at the Oncology Institute of Southern Switzerland in Bellinzona. Dr. Zucca presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

The results of the research underscore that “mediastinal radiation therapy in patients with complete remission after frontline immunochemotherapy can be safely omitted,” he said.

While PMBCL has a relatively low incidence, representing fewer than 5% of cases of non-Hodgkin lymphoma, the cancer is over-represented in young White women between approximately 30 and 40 years of age, and is a notably aggressive form of diffuse large B-cell lymphoma.

However, in patients who rapidly achieve remission with dose-intensive immunochemotherapy, the prognosis is good.

In such cases, the use of mediastinal radiation therapy has been seen as a measure to further consolidate the immunochemotherapy response, but the additional treatment comes at the cost of an increased risk of second malignancies, as well as coronary or valvular heart disease.

Meanwhile, in recent decades promising data has shown that aggressive chemoimmunotherapy regimens alone, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) can be enough for patients achieving a complete remission, while novel approaches such as checkpoint inhibitors and CAR T-cell therapy further show benefits in patients with lymphoma that relapses after treatment.

With ongoing controversy over whether to include the added radiation therapy among patients with a complete metabolic response, Dr. Zucca and his colleagues conducted the IELSG37 international study, enrolling 545 patients from 74 centers in 13 countries, including 336 women, with newly diagnosed PMBCL.

The patients were treated with induction chemoimmunotherapy with rituximab and anthracycline-based therapy based on local practice, and response assessed among of 530 of the 545 patients showed that 268 (50.6%) achieved a complete metabolic response.

Those patients were then randomized to either observation (n = 132) or consolidation radiation therapy (30 Gy; n = 136). The characteristics between the two groups were similar, with a mean age of 35.5, and about 65% female.

With a median follow-up of 63 months (range, 48-60 months), the primary endpoint of progression-free survival at 30 months was not significantly different between the observation arm (98.5%) and radiation therapy arm (96.2%; P = .278).

After adjustment for factors including sex, chemotherapy, country, and positron emission tomography (PET) response score, the estimated relative effect of radiotherapy versus observation was a hazard ratio of 0.68, and the absolute risk reduction associated with radiotherapy at 30 months was 1.2% after adjustment.

The number needed to treat is high, at 126.3 after stratification, and the 5-year overall survival was excellent in both arms, at 99%.

“What this tells us is that treatment with radiation therapy in well over 100 patients is needed just to avoid a single recurrence,” Dr. Zucca explained.

Overall survival after 3 years was excellent and identical in both arms, at about 99%.

To date, three severe cardiac events and three second cancers have been recorded in the study, all occurring among patients randomized to receive radiation therapy.

Dr. Zucca noted that longer follow-up is needed to better examine late toxicities.

“The long-term toxicities of mediastinal radiotherapy are well documented, particularly second breast, thyroid, and lung cancers and increased risk of coronary or valvular heart disease, in a patient group dominated by young adults,” Dr. Zucca said in a press statement.

“This study shows chemoimmunotherapy alone is an effective treatment for primary mediastinal B-cell lymphoma and strongly supports omitting radiotherapy without impacting chances of cure.”

Commenting on the study, Corey W. Speers, MD, PhD, assistant professor, radiation oncology, department of surgery, University of Michigan Hospital, Ann Arbor, said the findings have important clinical implications.

“We all should be encouraged by the low rates in this trial, which are lower than expected,” Dr. Speers said in a press briefing.

In further comments, he added that “these results will inform and likely change clinical practice.”

Dr. Speers said the study is notable for being the first of its kind.

“This clinical question has not previously been directly addressed, and this is the first study to do so,” he said.

“With more effective systemic therapies, many patients have their lymphoma disappear with early aggressive treatment, and although radiation is very effective at treating lymphoma, it has not been clear if it is needed in these patients that have an early rapid response to systemic therapy before starting radiation,” Dr. Speers explained.

“We have struggled as oncologists to know whether omitting this effective radiotherapy would compromise outcomes, and thus many were inclined to continue offering it to patients, even with the great early response. This study helps answer this critical question,” he said.

The results add reassuring evidence, buttressing efforts to avoid unnecessary interventions that may provide little or no benefit, Dr. Speers added.

“We are now in an era of ‘less being more’ as we seek ways to provide optimal quality and quantity of life to patients with cancer and their families, and this is just another example of the tremendous progress being made.”

Further commenting on the study at the press briefing, Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said the research supports ASCO’s ongoing efforts to reduce the toxicities of cancer treatment.

“Our ASCO vision is a world where cancer is either prevented or cured, and every patient is cured – and every survivor is healthy, and that part about every survivor being healthy is what we’re working on here [in this study],” Dr. Gralow said.

The study was funded by the Swiss Cancer League and Cancer Research UK, with partial support from the Swiss National Science Foundation. Dr. Zucca reported relationships with AstraZeneca, Beigene, Celgene, Incyte, Janssen, Merck, Roche, Celltrion Healthcare, Kite, and Abbvie. Dr. Speers disclosed his coinvention of technology that assesses radiosensitivity and predicts benefits from adjutant radiotherapy.

For patients with primary mediastinal B-cell lymphoma (PMBCL) who achieved a complete metabolic response after immunochemotherapy, radiation therapy may be safely omitted without heightening their risks of relapse or disease progression – thereby sparing them the toxicity and costs of this additional treatment.

“This study is the largest prospective study of PMBCL ever conducted,” said first author Emanuele Zucca, MD, consultant and head of the lymphoma unit at the Oncology Institute of Southern Switzerland in Bellinzona. Dr. Zucca presented the findings at the annual meeting of the American Society of Clinical Oncology (ASCO).

The results of the research underscore that “mediastinal radiation therapy in patients with complete remission after frontline immunochemotherapy can be safely omitted,” he said.

While PMBCL has a relatively low incidence, representing fewer than 5% of cases of non-Hodgkin lymphoma, the cancer is over-represented in young White women between approximately 30 and 40 years of age, and is a notably aggressive form of diffuse large B-cell lymphoma.

However, in patients who rapidly achieve remission with dose-intensive immunochemotherapy, the prognosis is good.

In such cases, the use of mediastinal radiation therapy has been seen as a measure to further consolidate the immunochemotherapy response, but the additional treatment comes at the cost of an increased risk of second malignancies, as well as coronary or valvular heart disease.

Meanwhile, in recent decades promising data has shown that aggressive chemoimmunotherapy regimens alone, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) can be enough for patients achieving a complete remission, while novel approaches such as checkpoint inhibitors and CAR T-cell therapy further show benefits in patients with lymphoma that relapses after treatment.

With ongoing controversy over whether to include the added radiation therapy among patients with a complete metabolic response, Dr. Zucca and his colleagues conducted the IELSG37 international study, enrolling 545 patients from 74 centers in 13 countries, including 336 women, with newly diagnosed PMBCL.

The patients were treated with induction chemoimmunotherapy with rituximab and anthracycline-based therapy based on local practice, and response assessed among of 530 of the 545 patients showed that 268 (50.6%) achieved a complete metabolic response.

Those patients were then randomized to either observation (n = 132) or consolidation radiation therapy (30 Gy; n = 136). The characteristics between the two groups were similar, with a mean age of 35.5, and about 65% female.

With a median follow-up of 63 months (range, 48-60 months), the primary endpoint of progression-free survival at 30 months was not significantly different between the observation arm (98.5%) and radiation therapy arm (96.2%; P = .278).

After adjustment for factors including sex, chemotherapy, country, and positron emission tomography (PET) response score, the estimated relative effect of radiotherapy versus observation was a hazard ratio of 0.68, and the absolute risk reduction associated with radiotherapy at 30 months was 1.2% after adjustment.

The number needed to treat is high, at 126.3 after stratification, and the 5-year overall survival was excellent in both arms, at 99%.

“What this tells us is that treatment with radiation therapy in well over 100 patients is needed just to avoid a single recurrence,” Dr. Zucca explained.

Overall survival after 3 years was excellent and identical in both arms, at about 99%.

To date, three severe cardiac events and three second cancers have been recorded in the study, all occurring among patients randomized to receive radiation therapy.

Dr. Zucca noted that longer follow-up is needed to better examine late toxicities.

“The long-term toxicities of mediastinal radiotherapy are well documented, particularly second breast, thyroid, and lung cancers and increased risk of coronary or valvular heart disease, in a patient group dominated by young adults,” Dr. Zucca said in a press statement.

“This study shows chemoimmunotherapy alone is an effective treatment for primary mediastinal B-cell lymphoma and strongly supports omitting radiotherapy without impacting chances of cure.”

Commenting on the study, Corey W. Speers, MD, PhD, assistant professor, radiation oncology, department of surgery, University of Michigan Hospital, Ann Arbor, said the findings have important clinical implications.

“We all should be encouraged by the low rates in this trial, which are lower than expected,” Dr. Speers said in a press briefing.

In further comments, he added that “these results will inform and likely change clinical practice.”

Dr. Speers said the study is notable for being the first of its kind.

“This clinical question has not previously been directly addressed, and this is the first study to do so,” he said.

“With more effective systemic therapies, many patients have their lymphoma disappear with early aggressive treatment, and although radiation is very effective at treating lymphoma, it has not been clear if it is needed in these patients that have an early rapid response to systemic therapy before starting radiation,” Dr. Speers explained.

“We have struggled as oncologists to know whether omitting this effective radiotherapy would compromise outcomes, and thus many were inclined to continue offering it to patients, even with the great early response. This study helps answer this critical question,” he said.

The results add reassuring evidence, buttressing efforts to avoid unnecessary interventions that may provide little or no benefit, Dr. Speers added.

“We are now in an era of ‘less being more’ as we seek ways to provide optimal quality and quantity of life to patients with cancer and their families, and this is just another example of the tremendous progress being made.”

Further commenting on the study at the press briefing, Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, said the research supports ASCO’s ongoing efforts to reduce the toxicities of cancer treatment.

“Our ASCO vision is a world where cancer is either prevented or cured, and every patient is cured – and every survivor is healthy, and that part about every survivor being healthy is what we’re working on here [in this study],” Dr. Gralow said.

The study was funded by the Swiss Cancer League and Cancer Research UK, with partial support from the Swiss National Science Foundation. Dr. Zucca reported relationships with AstraZeneca, Beigene, Celgene, Incyte, Janssen, Merck, Roche, Celltrion Healthcare, Kite, and Abbvie. Dr. Speers disclosed his coinvention of technology that assesses radiosensitivity and predicts benefits from adjutant radiotherapy.

Diffuse large B-cell lymphoma (DLBCL) made headlines earlier this year with the high-profile case of prominent U.S. Congressman Jamie Raskin (D-MD). Yet, until very recently, progress in treating this most common form of lymphoma has been stalled for more than 2 decades.

Significant breakthroughs have come in just the past few weeks and months, through the use of CAR T-cell and immunotherapies and with the approval in April by the Food and Drug Administration of polatuzumab for frontline DLBCL.

“Until the publishing of data from the POLARIX study (NCT03274492), which led to the approval of polatuzumab vedotin plus rituximab-cyclophosphamide, doxorubicin, and prednisone (pola + R-CHP), we had not had a breakthrough in frontline DLBCL therapies since the addition of rituximab 22 years ago,” said Dr. Charalambos Andreadis, MD, of the University of California at San Francisco’s Helen Diller Family Comprehensive Cancer Center.

University of California, San Francisco

“Pola + R-CHP is an improvement over the standard-of-care treatment, R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone), giving treatment naive patients an increase in PFS without an increase in side effects,” Dr. Andreadis said.

R-CHP-polatuzumab was approved only for patients with an International Prognostic Indices score between 2 and 5, leaving patients with IPI scores of 0 or 1 with the frontline standard of care (SoC) treatment of R-CHOP, which has a cure rate of between 60% and 70%.

“The highest likelihood of relapse is in the first year following treatment. After 2 years in remission, patients’ chance of relapsing is the same as the general populations’ chance of getting DLBCL for the first time. This is why even a slight increase in the progression-free survival rate with the addition of pola is so significant,” Dr. Andreadis noted.

Historically, patients with relapsed or refractory (RR) DLBCL who did not respond to R-CHOP or who experienced disease relapse less than a year after primary intervention were treated with alternative chemotherapy regimens, often followed by autologous stem cell transplants (ASCT). Randomized control studies have shown that CAR T-cell therapies yield higher success rates than chemotherapy and ASCT, leading to the SoC in RR patients being CAR-T cell therapy directly following failed primary treatment.

“There are many new CAR T-cell platforms in development, as well as novel combination strategies that aim to target critical genetic pathways,” Kieron Dunleavy, MD, professor of medicine at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital, said in an interview. “While access to CAR T-cell therapies is becoming easier and more feasible in many centers, fast access continues to be an issue for many patients, often depending on geography and socioeconomic factors.”

Asked about the latest breakthroughs in treating DLBCL, Dr. Dunleavy said, “A significant proportion of patients with relapsed or refractory DLBCL do not have easy access to CAR T-cell therapies, so this needs to be addressed and improved. Sometimes the rapidity of clinical progression in DLBCL can make these therapies challenging to deliver, considering logistical issues like apheresis and insurance approvals, which are frequently complex. This highlights the need for alternative and ‘easier to deliver’ CAR-T cells and our continued prioritization of developing alternative effective agents for DLBCL.

“Currently, commercially approved CAR T-cells in DLBCL target the CD-19 marker on lymphoma cells but CAR T-cells targeting other and more than one antigen as well as alternative anti CD19 agents like loncastuximab and tafasitamab are similarly FDA approved and available for patients,” Dr. Dunleavy concluded.

Dr. Dunleavy is affiliated with the MedStar Georgetown Lymphoma group, where Rep. Raskin publicly announced that he had completed 4 months of chemotherapy treatment for DLBCL. On April 27, in an open letter to the U.S. public, he wrote that he rang the bell at MedStar to mark his preliminary diagnosis of being “in remission,” with a “90% prognosis of no relapse.”

Interviewed about the latest advances in treating DLBCL, Jason Westin, MD, associate professor of lymphoma and myeloma at the MD Anderson Cancer Center in Houston, said that even with improvements in overall survival possible with CAR T-cell therapies, “usually, a clinical trial should be considered strongly, as it is often the best option for patients, both in a newly diagnosed or in a relapsed setting, as they allow access to tomorrow’s breakthrough therapies today.”

MD Anderson Cancer Center

Dr. Westin cited the example of bispecific T-cell engagers (BITE) as a promising therapy that is available to patients in clinical trials. These agents bind to one side to the lymphoma cell, but they also have a binding arm for T-cells, so they activate a patient’s own immune cells to kill lymphoma cells, in some cases offering a cure when CAR T-cell therapy has failed.

The first BITE to be approved, mosunetuzumab, is authorized only for the treatment of follicular lymphoma. However, data from a recent clinical study indicated that the agent yields complete responses in 24% of heavily pretreated patients with RR DLBCL.

Another BITE, glofitamab, was approved in Canada in March 2023 for use in RR DLBCL. Based on its high efficacy, it soon may be approved elsewhere.

Dr. Andreadis noted, “We are finally at a point where for both treatment naive and RR DLBCL patients, there are several promising options on the horizon that don’t involve ASCT. Furthermore, these breakthroughs reinforce each other, as there are studies in which therapies like BITE are being brought to the front line and pola to RR cases.”

The growing field of new frontline and RR DLBCL therapies lend credence to the optimism of specialists who treat DLBCL – and to the sanguine note that Congressman Raskin struck in published comments about his treatment for DLBCL.

Dr. Andreadis reported ties with BMS, Novartis, Roche, Genmab, Merck, Gilead, AbbVie, and J&J. Dr. Dunleavy disclosed relationships with ONO Pharmaceuticals, Kymera, Merck, Genentech, AstraZeneca, Amgen, ADC Therapeutics, MorphoSys and Incyte, Kite/Gilead, Cellectar. Dr. Westin reported ties with Kite/Gilead, BMS, Novartis, Genentech, AstraZeneca, Morphosys/Incyte, ADC Therapeutics, Kymera, Nurix, and MonteRosa.

Diffuse large B-cell lymphoma (DLBCL) made headlines earlier this year with the high-profile case of prominent U.S. Congressman Jamie Raskin (D-MD). Yet, until very recently, progress in treating this most common form of lymphoma has been stalled for more than 2 decades.

Significant breakthroughs have come in just the past few weeks and months, through the use of CAR T-cell and immunotherapies and with the approval in April by the Food and Drug Administration of polatuzumab for frontline DLBCL.

“Until the publishing of data from the POLARIX study (NCT03274492), which led to the approval of polatuzumab vedotin plus rituximab-cyclophosphamide, doxorubicin, and prednisone (pola + R-CHP), we had not had a breakthrough in frontline DLBCL therapies since the addition of rituximab 22 years ago,” said Dr. Charalambos Andreadis, MD, of the University of California at San Francisco’s Helen Diller Family Comprehensive Cancer Center.

University of California, San Francisco

“Pola + R-CHP is an improvement over the standard-of-care treatment, R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone), giving treatment naive patients an increase in PFS without an increase in side effects,” Dr. Andreadis said.

R-CHP-polatuzumab was approved only for patients with an International Prognostic Indices score between 2 and 5, leaving patients with IPI scores of 0 or 1 with the frontline standard of care (SoC) treatment of R-CHOP, which has a cure rate of between 60% and 70%.

“The highest likelihood of relapse is in the first year following treatment. After 2 years in remission, patients’ chance of relapsing is the same as the general populations’ chance of getting DLBCL for the first time. This is why even a slight increase in the progression-free survival rate with the addition of pola is so significant,” Dr. Andreadis noted.

Historically, patients with relapsed or refractory (RR) DLBCL who did not respond to R-CHOP or who experienced disease relapse less than a year after primary intervention were treated with alternative chemotherapy regimens, often followed by autologous stem cell transplants (ASCT). Randomized control studies have shown that CAR T-cell therapies yield higher success rates than chemotherapy and ASCT, leading to the SoC in RR patients being CAR-T cell therapy directly following failed primary treatment.

“There are many new CAR T-cell platforms in development, as well as novel combination strategies that aim to target critical genetic pathways,” Kieron Dunleavy, MD, professor of medicine at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital, said in an interview. “While access to CAR T-cell therapies is becoming easier and more feasible in many centers, fast access continues to be an issue for many patients, often depending on geography and socioeconomic factors.”

Asked about the latest breakthroughs in treating DLBCL, Dr. Dunleavy said, “A significant proportion of patients with relapsed or refractory DLBCL do not have easy access to CAR T-cell therapies, so this needs to be addressed and improved. Sometimes the rapidity of clinical progression in DLBCL can make these therapies challenging to deliver, considering logistical issues like apheresis and insurance approvals, which are frequently complex. This highlights the need for alternative and ‘easier to deliver’ CAR-T cells and our continued prioritization of developing alternative effective agents for DLBCL.

“Currently, commercially approved CAR T-cells in DLBCL target the CD-19 marker on lymphoma cells but CAR T-cells targeting other and more than one antigen as well as alternative anti CD19 agents like loncastuximab and tafasitamab are similarly FDA approved and available for patients,” Dr. Dunleavy concluded.

Dr. Dunleavy is affiliated with the MedStar Georgetown Lymphoma group, where Rep. Raskin publicly announced that he had completed 4 months of chemotherapy treatment for DLBCL. On April 27, in an open letter to the U.S. public, he wrote that he rang the bell at MedStar to mark his preliminary diagnosis of being “in remission,” with a “90% prognosis of no relapse.”

Interviewed about the latest advances in treating DLBCL, Jason Westin, MD, associate professor of lymphoma and myeloma at the MD Anderson Cancer Center in Houston, said that even with improvements in overall survival possible with CAR T-cell therapies, “usually, a clinical trial should be considered strongly, as it is often the best option for patients, both in a newly diagnosed or in a relapsed setting, as they allow access to tomorrow’s breakthrough therapies today.”

MD Anderson Cancer Center

Dr. Westin cited the example of bispecific T-cell engagers (BITE) as a promising therapy that is available to patients in clinical trials. These agents bind to one side to the lymphoma cell, but they also have a binding arm for T-cells, so they activate a patient’s own immune cells to kill lymphoma cells, in some cases offering a cure when CAR T-cell therapy has failed.

The first BITE to be approved, mosunetuzumab, is authorized only for the treatment of follicular lymphoma. However, data from a recent clinical study indicated that the agent yields complete responses in 24% of heavily pretreated patients with RR DLBCL.

Another BITE, glofitamab, was approved in Canada in March 2023 for use in RR DLBCL. Based on its high efficacy, it soon may be approved elsewhere.

Dr. Andreadis noted, “We are finally at a point where for both treatment naive and RR DLBCL patients, there are several promising options on the horizon that don’t involve ASCT. Furthermore, these breakthroughs reinforce each other, as there are studies in which therapies like BITE are being brought to the front line and pola to RR cases.”

The growing field of new frontline and RR DLBCL therapies lend credence to the optimism of specialists who treat DLBCL – and to the sanguine note that Congressman Raskin struck in published comments about his treatment for DLBCL.

Dr. Andreadis reported ties with BMS, Novartis, Roche, Genmab, Merck, Gilead, AbbVie, and J&J. Dr. Dunleavy disclosed relationships with ONO Pharmaceuticals, Kymera, Merck, Genentech, AstraZeneca, Amgen, ADC Therapeutics, MorphoSys and Incyte, Kite/Gilead, Cellectar. Dr. Westin reported ties with Kite/Gilead, BMS, Novartis, Genentech, AstraZeneca, Morphosys/Incyte, ADC Therapeutics, Kymera, Nurix, and MonteRosa.

Diffuse large B-cell lymphoma (DLBCL) made headlines earlier this year with the high-profile case of prominent U.S. Congressman Jamie Raskin (D-MD). Yet, until very recently, progress in treating this most common form of lymphoma has been stalled for more than 2 decades.

Significant breakthroughs have come in just the past few weeks and months, through the use of CAR T-cell and immunotherapies and with the approval in April by the Food and Drug Administration of polatuzumab for frontline DLBCL.

“Until the publishing of data from the POLARIX study (NCT03274492), which led to the approval of polatuzumab vedotin plus rituximab-cyclophosphamide, doxorubicin, and prednisone (pola + R-CHP), we had not had a breakthrough in frontline DLBCL therapies since the addition of rituximab 22 years ago,” said Dr. Charalambos Andreadis, MD, of the University of California at San Francisco’s Helen Diller Family Comprehensive Cancer Center.

University of California, San Francisco

“Pola + R-CHP is an improvement over the standard-of-care treatment, R-CHOP (rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone), giving treatment naive patients an increase in PFS without an increase in side effects,” Dr. Andreadis said.

R-CHP-polatuzumab was approved only for patients with an International Prognostic Indices score between 2 and 5, leaving patients with IPI scores of 0 or 1 with the frontline standard of care (SoC) treatment of R-CHOP, which has a cure rate of between 60% and 70%.

“The highest likelihood of relapse is in the first year following treatment. After 2 years in remission, patients’ chance of relapsing is the same as the general populations’ chance of getting DLBCL for the first time. This is why even a slight increase in the progression-free survival rate with the addition of pola is so significant,” Dr. Andreadis noted.

Historically, patients with relapsed or refractory (RR) DLBCL who did not respond to R-CHOP or who experienced disease relapse less than a year after primary intervention were treated with alternative chemotherapy regimens, often followed by autologous stem cell transplants (ASCT). Randomized control studies have shown that CAR T-cell therapies yield higher success rates than chemotherapy and ASCT, leading to the SoC in RR patients being CAR-T cell therapy directly following failed primary treatment.

“There are many new CAR T-cell platforms in development, as well as novel combination strategies that aim to target critical genetic pathways,” Kieron Dunleavy, MD, professor of medicine at the Lombardi Comprehensive Cancer Center at Georgetown University Hospital, said in an interview. “While access to CAR T-cell therapies is becoming easier and more feasible in many centers, fast access continues to be an issue for many patients, often depending on geography and socioeconomic factors.”

Asked about the latest breakthroughs in treating DLBCL, Dr. Dunleavy said, “A significant proportion of patients with relapsed or refractory DLBCL do not have easy access to CAR T-cell therapies, so this needs to be addressed and improved. Sometimes the rapidity of clinical progression in DLBCL can make these therapies challenging to deliver, considering logistical issues like apheresis and insurance approvals, which are frequently complex. This highlights the need for alternative and ‘easier to deliver’ CAR-T cells and our continued prioritization of developing alternative effective agents for DLBCL.

“Currently, commercially approved CAR T-cells in DLBCL target the CD-19 marker on lymphoma cells but CAR T-cells targeting other and more than one antigen as well as alternative anti CD19 agents like loncastuximab and tafasitamab are similarly FDA approved and available for patients,” Dr. Dunleavy concluded.

Dr. Dunleavy is affiliated with the MedStar Georgetown Lymphoma group, where Rep. Raskin publicly announced that he had completed 4 months of chemotherapy treatment for DLBCL. On April 27, in an open letter to the U.S. public, he wrote that he rang the bell at MedStar to mark his preliminary diagnosis of being “in remission,” with a “90% prognosis of no relapse.”

Interviewed about the latest advances in treating DLBCL, Jason Westin, MD, associate professor of lymphoma and myeloma at the MD Anderson Cancer Center in Houston, said that even with improvements in overall survival possible with CAR T-cell therapies, “usually, a clinical trial should be considered strongly, as it is often the best option for patients, both in a newly diagnosed or in a relapsed setting, as they allow access to tomorrow’s breakthrough therapies today.”

MD Anderson Cancer Center

Dr. Westin cited the example of bispecific T-cell engagers (BITE) as a promising therapy that is available to patients in clinical trials. These agents bind to one side to the lymphoma cell, but they also have a binding arm for T-cells, so they activate a patient’s own immune cells to kill lymphoma cells, in some cases offering a cure when CAR T-cell therapy has failed.

The first BITE to be approved, mosunetuzumab, is authorized only for the treatment of follicular lymphoma. However, data from a recent clinical study indicated that the agent yields complete responses in 24% of heavily pretreated patients with RR DLBCL.

Another BITE, glofitamab, was approved in Canada in March 2023 for use in RR DLBCL. Based on its high efficacy, it soon may be approved elsewhere.

Dr. Andreadis noted, “We are finally at a point where for both treatment naive and RR DLBCL patients, there are several promising options on the horizon that don’t involve ASCT. Furthermore, these breakthroughs reinforce each other, as there are studies in which therapies like BITE are being brought to the front line and pola to RR cases.”

The growing field of new frontline and RR DLBCL therapies lend credence to the optimism of specialists who treat DLBCL – and to the sanguine note that Congressman Raskin struck in published comments about his treatment for DLBCL.

Dr. Andreadis reported ties with BMS, Novartis, Roche, Genmab, Merck, Gilead, AbbVie, and J&J. Dr. Dunleavy disclosed relationships with ONO Pharmaceuticals, Kymera, Merck, Genentech, AstraZeneca, Amgen, ADC Therapeutics, MorphoSys and Incyte, Kite/Gilead, Cellectar. Dr. Westin reported ties with Kite/Gilead, BMS, Novartis, Genentech, AstraZeneca, Morphosys/Incyte, ADC Therapeutics, Kymera, Nurix, and MonteRosa.