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Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

There was a remarkable reduction in bowel and urinary side effects when MRI was used instead of CT to guide stereotactic body radiotherapy (SBRT) for localized prostate cancer, shows a study from the University of California, Los Angeles.

Among the first 100 men in the phase 3 MIRAGE trial (Magnetic Resonance Imaging–Guided Versus Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer), MRI guidance more than halved the incidence of grade 2 or higher physician-reported genitourinary toxicity within 90 days of the procedure, which fell from 47.1% with CT to 22.4% with MRI.

While 13.7% of men had gastrointestinal complications with CT guidance, there wasn’t a single case in the MRI arm. The findings were presented Feb. 17 at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The investigators thought they’d need 300 men to detect a safety difference, but the results are so strong that they’ve scaled back enrollment to 154. In the meantime, MRI-guided SBRT is now offered routinely to men with localized prostate cancer at UCLA.

“Our final results are expected later this year, but we are extremely optimistic by what we’re seeing, and hope this technology will soon begin to offer men undergoing radiotherapy for prostate cancer better outcomes,” said lead investigator Amar Upadhyaya Kishan, MD, a genitourinary oncology radiologist, in a UCLA press release.

The better outcomes are caused by the enhanced imaging capabilities of MRI, including real time tracking and automatic beam shutoff when the prostate moves too far outside of the treatment boundary, Dr. Kishan explained on Twitter.

Because of the extra precision, “we felt we could safely reduce the planning margins to only 2 mm” with MRI, down from 4 mm with CT. It translated to smaller treatment volumes and less collateral tissue damage, he said.

Across the first 100 subjects, 49 men were randomized to MRI-guided SBRT and 51 to SBRT with CT guidance. Their prostates and proximal seminal vesicles were dosed with 40 Gy of radiation in five fractions. Rectal spacing and nodal irradiation were at physician discretion.

Patients in the MRI arm also reported significantly fewer urinary symptoms, including urgency, incontinence, burning sensations, and bowel dysfunction, such as pain, diarrhea, and obstruction, among others, at 1 month with MRI guidance. The differences diminished at 3 months with adverse event management in the CT arm.

Lymph nodes were irradiated in 29% of men in the CT group versus 20% in the MRI arm, and 37% of the CT group versus 27% with MRI had rectal spacing.

Baseline gland size was a median of 39 mL in both groups. Baseline International Prostate Symptom Scores were a median of 8 points in the MRI group but 5 points in the CT arm.

The work was funded by UCLA, among others. Dr. Kishan has ownership interests in ViewRay, the company that makes the MRI-guiding technology used in the trial, and reported honoraria and research funding from the company.

There was a remarkable reduction in bowel and urinary side effects when MRI was used instead of CT to guide stereotactic body radiotherapy (SBRT) for localized prostate cancer, shows a study from the University of California, Los Angeles.

Among the first 100 men in the phase 3 MIRAGE trial (Magnetic Resonance Imaging–Guided Versus Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer), MRI guidance more than halved the incidence of grade 2 or higher physician-reported genitourinary toxicity within 90 days of the procedure, which fell from 47.1% with CT to 22.4% with MRI.

While 13.7% of men had gastrointestinal complications with CT guidance, there wasn’t a single case in the MRI arm. The findings were presented Feb. 17 at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The investigators thought they’d need 300 men to detect a safety difference, but the results are so strong that they’ve scaled back enrollment to 154. In the meantime, MRI-guided SBRT is now offered routinely to men with localized prostate cancer at UCLA.

“Our final results are expected later this year, but we are extremely optimistic by what we’re seeing, and hope this technology will soon begin to offer men undergoing radiotherapy for prostate cancer better outcomes,” said lead investigator Amar Upadhyaya Kishan, MD, a genitourinary oncology radiologist, in a UCLA press release.

The better outcomes are caused by the enhanced imaging capabilities of MRI, including real time tracking and automatic beam shutoff when the prostate moves too far outside of the treatment boundary, Dr. Kishan explained on Twitter.

Because of the extra precision, “we felt we could safely reduce the planning margins to only 2 mm” with MRI, down from 4 mm with CT. It translated to smaller treatment volumes and less collateral tissue damage, he said.

Across the first 100 subjects, 49 men were randomized to MRI-guided SBRT and 51 to SBRT with CT guidance. Their prostates and proximal seminal vesicles were dosed with 40 Gy of radiation in five fractions. Rectal spacing and nodal irradiation were at physician discretion.

Patients in the MRI arm also reported significantly fewer urinary symptoms, including urgency, incontinence, burning sensations, and bowel dysfunction, such as pain, diarrhea, and obstruction, among others, at 1 month with MRI guidance. The differences diminished at 3 months with adverse event management in the CT arm.

Lymph nodes were irradiated in 29% of men in the CT group versus 20% in the MRI arm, and 37% of the CT group versus 27% with MRI had rectal spacing.

Baseline gland size was a median of 39 mL in both groups. Baseline International Prostate Symptom Scores were a median of 8 points in the MRI group but 5 points in the CT arm.

The work was funded by UCLA, among others. Dr. Kishan has ownership interests in ViewRay, the company that makes the MRI-guiding technology used in the trial, and reported honoraria and research funding from the company.

There was a remarkable reduction in bowel and urinary side effects when MRI was used instead of CT to guide stereotactic body radiotherapy (SBRT) for localized prostate cancer, shows a study from the University of California, Los Angeles.

Among the first 100 men in the phase 3 MIRAGE trial (Magnetic Resonance Imaging–Guided Versus Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer), MRI guidance more than halved the incidence of grade 2 or higher physician-reported genitourinary toxicity within 90 days of the procedure, which fell from 47.1% with CT to 22.4% with MRI.

While 13.7% of men had gastrointestinal complications with CT guidance, there wasn’t a single case in the MRI arm. The findings were presented Feb. 17 at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The investigators thought they’d need 300 men to detect a safety difference, but the results are so strong that they’ve scaled back enrollment to 154. In the meantime, MRI-guided SBRT is now offered routinely to men with localized prostate cancer at UCLA.

“Our final results are expected later this year, but we are extremely optimistic by what we’re seeing, and hope this technology will soon begin to offer men undergoing radiotherapy for prostate cancer better outcomes,” said lead investigator Amar Upadhyaya Kishan, MD, a genitourinary oncology radiologist, in a UCLA press release.

The better outcomes are caused by the enhanced imaging capabilities of MRI, including real time tracking and automatic beam shutoff when the prostate moves too far outside of the treatment boundary, Dr. Kishan explained on Twitter.

Because of the extra precision, “we felt we could safely reduce the planning margins to only 2 mm” with MRI, down from 4 mm with CT. It translated to smaller treatment volumes and less collateral tissue damage, he said.

Across the first 100 subjects, 49 men were randomized to MRI-guided SBRT and 51 to SBRT with CT guidance. Their prostates and proximal seminal vesicles were dosed with 40 Gy of radiation in five fractions. Rectal spacing and nodal irradiation were at physician discretion.

Patients in the MRI arm also reported significantly fewer urinary symptoms, including urgency, incontinence, burning sensations, and bowel dysfunction, such as pain, diarrhea, and obstruction, among others, at 1 month with MRI guidance. The differences diminished at 3 months with adverse event management in the CT arm.

Lymph nodes were irradiated in 29% of men in the CT group versus 20% in the MRI arm, and 37% of the CT group versus 27% with MRI had rectal spacing.

Baseline gland size was a median of 39 mL in both groups. Baseline International Prostate Symptom Scores were a median of 8 points in the MRI group but 5 points in the CT arm.

The work was funded by UCLA, among others. Dr. Kishan has ownership interests in ViewRay, the company that makes the MRI-guiding technology used in the trial, and reported honoraria and research funding from the company.

Women with early-stage breast cancer who are poorly represented in clinical trials have worse survival than their well-represented peers, according to a real-world analysis.

The study shows that more than half of women with early breast cancer are not well represented in clinical trials because of age, comorbidities, or race, yet they receive therapies based on the results of these trials.

“The most interesting finding is that patients with comorbidities resulting in lab abnormalities that would typically exclude them from receiving medication on a trial are still frequently receiving these medications and have an almost threefold higher mortality,” Gabrielle Rocque, MD, with the division of hematology and oncology, University of Alabama at Birmingham, told this news organization.

“We need to do a deeper dive to better understand what is driving this mortality difference and test specific medications in patients with these conditions to understand the optimal treatment for this population,” Dr. Rocque added.

The study was published Feb. 1 in JCO Oncology Practice.

Many patient groups are not well represented in clinical trials, including patients of color, older patients, and those with comorbidities, and it remains unclear how treatment outcomes may differ among these patients, compared with those who are well represented in trials.

To investigate, Dr. Rocque and colleagues looked at 11,770 women diagnosed with stage I-III breast cancer between 2005 and 2015 in the American Society of Clinical Oncology CancerLinQ database.

White women between 45 and 69 years of age with no comorbid conditions were considered well represented and made up 48% of the cohort.

Non-White women and/or those younger than 45 years or older than 70 were considered under represented and made up 45% of the cohort. The unrepresented group (7%) included women with comorbidities – such as liver disease, renal insufficiency, thrombocytopenia, anemia, or uncontrolled diabetes – or concurrent cancer.

The majority of the women received a high-intensity chemotherapy regimen, including 58% of unrepresented, 66% of underrepresented, and 63% of well-represented patients.

Compared with well-represented women, unrepresented women had a higher risk of death at 5 years (adjusted hazard ratio, 2.71; 95% confidence interval, 2.08-3.52).

Overall, the team found no significant increase in the risk of death at 5 years in underrepresented vs. well-represented women (aHR, 1.19; 95% CI, 0.98-1.45). However, that risk varied with age. Among underrepresented women, those aged 70 and older had more than a twofold higher risk of 5-year mortality (aHR, 2.21), while those younger than 45 had a lower risk of 5-year mortality (aHR, 0.63), compared with those aged 45-69 years.

For three cancer subtypes, unrepresented patients had a greater than twofold higher risk of 5-year mortality, compared with well-represented patients (aHR, 2.50 for HER2-positive disease; aHR, 2.54 for HR-positive/HER2-negative disease; and aHR, 2.75 for triple-negative disease).

Underrepresented patients with HR-positive/HER2-negative disease had a 38% increased risk of 5-year mortality, compared with their well-represented peers (aHR, 1.38). However, there were no significant differences in 5-year mortality for underrepresented vs. well-represented patients with HER2-positive or triple-negative subtypes.
 

Risky business?

This analysis shows that unrepresented populations receive common treatment regimens at a similar rate as well-represented patients, the researchers note.

“By excluding patients with differing clinical conditions from trials but including them in the population to which drugs can be disseminated, one runs the risk of inadvertently causing injury,” the authors caution.

“To inform the practice of evidence-based medicine in an equitable manner, our findings support a need to both expand clinical trial inclusion criteria and report on clinical trial outcomes by clinical and demographic characteristics,” Dr. Rocque and colleagues conclude.

Charles Shapiro, MD, professor of medicine, hematology, and medical oncology, Icahn School of Medicine at Mount Sinai, New York, is not surprised by the findings of this study.

“We know that clinical trials are too restrictive and include only a selected population largely without comorbidities, but in the real world, people have comorbidities,” Dr. Shapiro, who was not involved in the research, told this news organization.

The study “starkly illustrates” the poorer survival of populations not represented in clinical trials.

“It could be that we need to change clinical trials, maybe ask fewer questions or maybe ask more important questions and loosen the eligibility up, because in the real world, there are people with comorbidities and people who are over 70,” Dr. Shapiro stated.

Are strides being made to change that? “Not really,” Dr. Shapiro said in an interview.

The study was supported by grants from the Robert Wood Johnson Foundation and the American Cancer Society. Dr. Rocque has served as a consultant or advisor for Pfizer; has received research funding from Carevive Systems, Genentech, and Pfizer; and has received travel, accommodations, and expenses from Carevive. Dr. Shapiro has financial relationships with UptoDate, 2nd MD, and Anthenum.

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

Women with early-stage breast cancer who are poorly represented in clinical trials have worse survival than their well-represented peers, according to a real-world analysis.

The study shows that more than half of women with early breast cancer are not well represented in clinical trials because of age, comorbidities, or race, yet they receive therapies based on the results of these trials.

“The most interesting finding is that patients with comorbidities resulting in lab abnormalities that would typically exclude them from receiving medication on a trial are still frequently receiving these medications and have an almost threefold higher mortality,” Gabrielle Rocque, MD, with the division of hematology and oncology, University of Alabama at Birmingham, told this news organization.

“We need to do a deeper dive to better understand what is driving this mortality difference and test specific medications in patients with these conditions to understand the optimal treatment for this population,” Dr. Rocque added.

The study was published Feb. 1 in JCO Oncology Practice.

Many patient groups are not well represented in clinical trials, including patients of color, older patients, and those with comorbidities, and it remains unclear how treatment outcomes may differ among these patients, compared with those who are well represented in trials.

To investigate, Dr. Rocque and colleagues looked at 11,770 women diagnosed with stage I-III breast cancer between 2005 and 2015 in the American Society of Clinical Oncology CancerLinQ database.

White women between 45 and 69 years of age with no comorbid conditions were considered well represented and made up 48% of the cohort.

Non-White women and/or those younger than 45 years or older than 70 were considered under represented and made up 45% of the cohort. The unrepresented group (7%) included women with comorbidities – such as liver disease, renal insufficiency, thrombocytopenia, anemia, or uncontrolled diabetes – or concurrent cancer.

The majority of the women received a high-intensity chemotherapy regimen, including 58% of unrepresented, 66% of underrepresented, and 63% of well-represented patients.

Compared with well-represented women, unrepresented women had a higher risk of death at 5 years (adjusted hazard ratio, 2.71; 95% confidence interval, 2.08-3.52).

Overall, the team found no significant increase in the risk of death at 5 years in underrepresented vs. well-represented women (aHR, 1.19; 95% CI, 0.98-1.45). However, that risk varied with age. Among underrepresented women, those aged 70 and older had more than a twofold higher risk of 5-year mortality (aHR, 2.21), while those younger than 45 had a lower risk of 5-year mortality (aHR, 0.63), compared with those aged 45-69 years.

For three cancer subtypes, unrepresented patients had a greater than twofold higher risk of 5-year mortality, compared with well-represented patients (aHR, 2.50 for HER2-positive disease; aHR, 2.54 for HR-positive/HER2-negative disease; and aHR, 2.75 for triple-negative disease).

Underrepresented patients with HR-positive/HER2-negative disease had a 38% increased risk of 5-year mortality, compared with their well-represented peers (aHR, 1.38). However, there were no significant differences in 5-year mortality for underrepresented vs. well-represented patients with HER2-positive or triple-negative subtypes.
 

Risky business?

This analysis shows that unrepresented populations receive common treatment regimens at a similar rate as well-represented patients, the researchers note.

“By excluding patients with differing clinical conditions from trials but including them in the population to which drugs can be disseminated, one runs the risk of inadvertently causing injury,” the authors caution.

“To inform the practice of evidence-based medicine in an equitable manner, our findings support a need to both expand clinical trial inclusion criteria and report on clinical trial outcomes by clinical and demographic characteristics,” Dr. Rocque and colleagues conclude.

Charles Shapiro, MD, professor of medicine, hematology, and medical oncology, Icahn School of Medicine at Mount Sinai, New York, is not surprised by the findings of this study.

“We know that clinical trials are too restrictive and include only a selected population largely without comorbidities, but in the real world, people have comorbidities,” Dr. Shapiro, who was not involved in the research, told this news organization.

The study “starkly illustrates” the poorer survival of populations not represented in clinical trials.

“It could be that we need to change clinical trials, maybe ask fewer questions or maybe ask more important questions and loosen the eligibility up, because in the real world, there are people with comorbidities and people who are over 70,” Dr. Shapiro stated.

Are strides being made to change that? “Not really,” Dr. Shapiro said in an interview.

The study was supported by grants from the Robert Wood Johnson Foundation and the American Cancer Society. Dr. Rocque has served as a consultant or advisor for Pfizer; has received research funding from Carevive Systems, Genentech, and Pfizer; and has received travel, accommodations, and expenses from Carevive. Dr. Shapiro has financial relationships with UptoDate, 2nd MD, and Anthenum.

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

Women with early-stage breast cancer who are poorly represented in clinical trials have worse survival than their well-represented peers, according to a real-world analysis.

The study shows that more than half of women with early breast cancer are not well represented in clinical trials because of age, comorbidities, or race, yet they receive therapies based on the results of these trials.

“The most interesting finding is that patients with comorbidities resulting in lab abnormalities that would typically exclude them from receiving medication on a trial are still frequently receiving these medications and have an almost threefold higher mortality,” Gabrielle Rocque, MD, with the division of hematology and oncology, University of Alabama at Birmingham, told this news organization.

“We need to do a deeper dive to better understand what is driving this mortality difference and test specific medications in patients with these conditions to understand the optimal treatment for this population,” Dr. Rocque added.

The study was published Feb. 1 in JCO Oncology Practice.

Many patient groups are not well represented in clinical trials, including patients of color, older patients, and those with comorbidities, and it remains unclear how treatment outcomes may differ among these patients, compared with those who are well represented in trials.

To investigate, Dr. Rocque and colleagues looked at 11,770 women diagnosed with stage I-III breast cancer between 2005 and 2015 in the American Society of Clinical Oncology CancerLinQ database.

White women between 45 and 69 years of age with no comorbid conditions were considered well represented and made up 48% of the cohort.

Non-White women and/or those younger than 45 years or older than 70 were considered under represented and made up 45% of the cohort. The unrepresented group (7%) included women with comorbidities – such as liver disease, renal insufficiency, thrombocytopenia, anemia, or uncontrolled diabetes – or concurrent cancer.

The majority of the women received a high-intensity chemotherapy regimen, including 58% of unrepresented, 66% of underrepresented, and 63% of well-represented patients.

Compared with well-represented women, unrepresented women had a higher risk of death at 5 years (adjusted hazard ratio, 2.71; 95% confidence interval, 2.08-3.52).

Overall, the team found no significant increase in the risk of death at 5 years in underrepresented vs. well-represented women (aHR, 1.19; 95% CI, 0.98-1.45). However, that risk varied with age. Among underrepresented women, those aged 70 and older had more than a twofold higher risk of 5-year mortality (aHR, 2.21), while those younger than 45 had a lower risk of 5-year mortality (aHR, 0.63), compared with those aged 45-69 years.

For three cancer subtypes, unrepresented patients had a greater than twofold higher risk of 5-year mortality, compared with well-represented patients (aHR, 2.50 for HER2-positive disease; aHR, 2.54 for HR-positive/HER2-negative disease; and aHR, 2.75 for triple-negative disease).

Underrepresented patients with HR-positive/HER2-negative disease had a 38% increased risk of 5-year mortality, compared with their well-represented peers (aHR, 1.38). However, there were no significant differences in 5-year mortality for underrepresented vs. well-represented patients with HER2-positive or triple-negative subtypes.
 

Risky business?

This analysis shows that unrepresented populations receive common treatment regimens at a similar rate as well-represented patients, the researchers note.

“By excluding patients with differing clinical conditions from trials but including them in the population to which drugs can be disseminated, one runs the risk of inadvertently causing injury,” the authors caution.

“To inform the practice of evidence-based medicine in an equitable manner, our findings support a need to both expand clinical trial inclusion criteria and report on clinical trial outcomes by clinical and demographic characteristics,” Dr. Rocque and colleagues conclude.

Charles Shapiro, MD, professor of medicine, hematology, and medical oncology, Icahn School of Medicine at Mount Sinai, New York, is not surprised by the findings of this study.

“We know that clinical trials are too restrictive and include only a selected population largely without comorbidities, but in the real world, people have comorbidities,” Dr. Shapiro, who was not involved in the research, told this news organization.

The study “starkly illustrates” the poorer survival of populations not represented in clinical trials.

“It could be that we need to change clinical trials, maybe ask fewer questions or maybe ask more important questions and loosen the eligibility up, because in the real world, there are people with comorbidities and people who are over 70,” Dr. Shapiro stated.

Are strides being made to change that? “Not really,” Dr. Shapiro said in an interview.

The study was supported by grants from the Robert Wood Johnson Foundation and the American Cancer Society. Dr. Rocque has served as a consultant or advisor for Pfizer; has received research funding from Carevive Systems, Genentech, and Pfizer; and has received travel, accommodations, and expenses from Carevive. Dr. Shapiro has financial relationships with UptoDate, 2nd MD, and Anthenum.

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

Twitter was all abuzz over an exchange that occurred Feb. 17 during the question-and-answer discussion that followed oral abstract presentations at the ASCO Genitourinary Cancers Symposium, held in San Francisco and also online. One of the panelists was accused of being less than professional in handling questions from the floor.

It began with a tweet from Sumanta Pal, MD, of the City of Hope, when he called out the behavior, although he did not identify the perpetrator.

“Yesterday we saw some reprehensible behavior emanating from the @ASCO #GU22 podium, with a well known investigator insulting (in a manner deeply imbued w microaggressions) an esteemed colleague at the mic. It’s a teachable moment & the lesson is simple: be kind to ur colleagues.”

It was not immediately clear what had occurred, and several people asked him to identify the people involved. One physician responded, “If it was bad enough to infer and share on Twitter, name the name.”

But even without details, the post provoked a reaction.

Erika Hamilton, MD, wrote, “I am not aware of this incident, but I always wonder ... if someone would do that from the podium, what would they/have they done and said when they didn’t think everyone was watching?”

Another tweet questioned why there were no codes of conduct in place, so that situations like this one wouldn’t happen.

“[It is] about time professional societies had codes of conduct in place for invited speakers, moderators of sessions etc,” wrote Deborah Verran, MD. “Then if it is breached the individual concerned is not invited back. This kind of incident also needs to be mentioned as part of the conference feedback process.”

As the number of clinicians chiming in increased, it soon became apparent that others were aware of the incident, and one posted a video clip, putting the mystery to rest.
 

Moderator quips, ‘Behave ... children’

The exchange occurred immediately following the oral abstract presentations on prostate cancer on Feb. 17. Two of these abstracts featured new data from large clinical trials investigating the use of PARP inhibitors in metastatic prostate cancer, which had slightly different results, leading to some debate. The PROpel trial with olaparib showed a benefit in all patients, irrespective of gene mutation status, but the MAGNITUDE trial with niraparib showed a benefit only in patients with gene alterations, and especially in those with BRCA1/2 mutations.

The invited discussant, Celestia Higano, MD, from the University of British Columbia, Vancouver, compared and contrasted the two trials and the differing results.

During the question-and-answer session that followed, Neeraj Agarwal, MD, from the Huntsman Cancer Institute, University of Utah, directed a question to Fred Saad, MD, who had presented the results of the PROpel trial.*

“As a practicing oncologist, I am very intrigued by the different results of the MAGNITUDE and PROpel trials. I am trying to figure out what do I do in my practice,” Dr. Agarwal began.

He continued on, explaining that he didn’t think that olaparib and niraparib were that different from one another for the two studies to have such differing results, when both of the drugs were given in combination with abiraterone.

The inclusion criteria for PROpel stipulated that patients undergo testing by ctDNA to determine if they were biomarker positive or not, but he pointed out that it is possible for testing to miss patients who might otherwise be positive for homologous recombination repair (HRR) gene alterations. He posed the question, could some of the patients deemed biomarker negative in fact have been positive but whose status was not detected by ctDNA testing?

At that point, Dr. Higano interrupted him before he had completed his question and asked, “Can I make a comment? Were you listening to my discussion?”

She then continued, pointing out that “you can’t talk about comparing olaparib and niraparib – these two trials had two very different populations.”

She emphasized that this was about the combinations in the populations being studied and not about olaparib and niraparib. “I clearly wasn’t very clear,” she said.

Dr. Agarwal then repeated that he wanted to know what to do with his patients and asked again about the accuracy of ctDNA testing.

“That’s a good question,” Dr. Higano said, “But the other comments you made weren’t.”

At that point, the moderator chimed in. “Let’s all calm down ... children.”

After a brief applause following the moderator’s comment, Dr. Saad then addressed the question.

When the video clip of this exchange was posted, a flood of tweets poured in, supporting Dr. Pal’s initial summation of the situation.

Alison Birtle, MD, tweeted, “I’m even more appalled having seen this exchange. Unacceptable. You don’t humiliate either the speaker or the delegate and the questions were entirely valid in my opinion. Basically what do I do tomorrow with these data so why ask were you listening. That’s just rude.”

Jason Kovac, MD, tweeted: “It’s absolutely not a proper way to behave. Whether it’s behind the scenes or to your face. You can hear the arrogance from everyone including the moderator with his children comment. This is the true face of medicine.”

Jarey Wang, MD, PhD, however, liked the moderator’s input. “Love it. ‘Let’s all calm down children.’ Good for the moderator.”

Several of the physicians who commented thought that the issue should have been addressed at the time it happened. Don S. Dizon, MD, wrote, “Calling out microagressions as they occur is so important. And very difficult. Agree, the teachable moment must be met with bravery. But it should happen in real time too.”

After 2 days of bantering on Twitter, with the thread growing increasingly longer and with the vast majority of posts supporting Dr. Pal’s initial assessment, Dr. Higano finally entered the discussion and defended her comments: “What you do not know is that the questioner and I are good colleagues,” she tweeted. “I have been involved in two of his academic promotions. My main concern was his comment re: how the two trials could have ‘so different results with the same combination.’ I sought to rectify wrong message.”

There were no direct replies to Dr. Higano’s tweet.

Perhaps the line to draw under this affair is the tweet from Simon Kim, MD, MPH, who wrote: “We can do better!”

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

Correction, 2/24/22: Dr. Fred Saad's name was misstated in an earlier version of this article.

Twitter was all abuzz over an exchange that occurred Feb. 17 during the question-and-answer discussion that followed oral abstract presentations at the ASCO Genitourinary Cancers Symposium, held in San Francisco and also online. One of the panelists was accused of being less than professional in handling questions from the floor.

It began with a tweet from Sumanta Pal, MD, of the City of Hope, when he called out the behavior, although he did not identify the perpetrator.

“Yesterday we saw some reprehensible behavior emanating from the @ASCO #GU22 podium, with a well known investigator insulting (in a manner deeply imbued w microaggressions) an esteemed colleague at the mic. It’s a teachable moment & the lesson is simple: be kind to ur colleagues.”

It was not immediately clear what had occurred, and several people asked him to identify the people involved. One physician responded, “If it was bad enough to infer and share on Twitter, name the name.”

But even without details, the post provoked a reaction.

Erika Hamilton, MD, wrote, “I am not aware of this incident, but I always wonder ... if someone would do that from the podium, what would they/have they done and said when they didn’t think everyone was watching?”

Another tweet questioned why there were no codes of conduct in place, so that situations like this one wouldn’t happen.

“[It is] about time professional societies had codes of conduct in place for invited speakers, moderators of sessions etc,” wrote Deborah Verran, MD. “Then if it is breached the individual concerned is not invited back. This kind of incident also needs to be mentioned as part of the conference feedback process.”

As the number of clinicians chiming in increased, it soon became apparent that others were aware of the incident, and one posted a video clip, putting the mystery to rest.
 

Moderator quips, ‘Behave ... children’

The exchange occurred immediately following the oral abstract presentations on prostate cancer on Feb. 17. Two of these abstracts featured new data from large clinical trials investigating the use of PARP inhibitors in metastatic prostate cancer, which had slightly different results, leading to some debate. The PROpel trial with olaparib showed a benefit in all patients, irrespective of gene mutation status, but the MAGNITUDE trial with niraparib showed a benefit only in patients with gene alterations, and especially in those with BRCA1/2 mutations.

The invited discussant, Celestia Higano, MD, from the University of British Columbia, Vancouver, compared and contrasted the two trials and the differing results.

During the question-and-answer session that followed, Neeraj Agarwal, MD, from the Huntsman Cancer Institute, University of Utah, directed a question to Fred Saad, MD, who had presented the results of the PROpel trial.*

“As a practicing oncologist, I am very intrigued by the different results of the MAGNITUDE and PROpel trials. I am trying to figure out what do I do in my practice,” Dr. Agarwal began.

He continued on, explaining that he didn’t think that olaparib and niraparib were that different from one another for the two studies to have such differing results, when both of the drugs were given in combination with abiraterone.

The inclusion criteria for PROpel stipulated that patients undergo testing by ctDNA to determine if they were biomarker positive or not, but he pointed out that it is possible for testing to miss patients who might otherwise be positive for homologous recombination repair (HRR) gene alterations. He posed the question, could some of the patients deemed biomarker negative in fact have been positive but whose status was not detected by ctDNA testing?

At that point, Dr. Higano interrupted him before he had completed his question and asked, “Can I make a comment? Were you listening to my discussion?”

She then continued, pointing out that “you can’t talk about comparing olaparib and niraparib – these two trials had two very different populations.”

She emphasized that this was about the combinations in the populations being studied and not about olaparib and niraparib. “I clearly wasn’t very clear,” she said.

Dr. Agarwal then repeated that he wanted to know what to do with his patients and asked again about the accuracy of ctDNA testing.

“That’s a good question,” Dr. Higano said, “But the other comments you made weren’t.”

At that point, the moderator chimed in. “Let’s all calm down ... children.”

After a brief applause following the moderator’s comment, Dr. Saad then addressed the question.

When the video clip of this exchange was posted, a flood of tweets poured in, supporting Dr. Pal’s initial summation of the situation.

Alison Birtle, MD, tweeted, “I’m even more appalled having seen this exchange. Unacceptable. You don’t humiliate either the speaker or the delegate and the questions were entirely valid in my opinion. Basically what do I do tomorrow with these data so why ask were you listening. That’s just rude.”

Jason Kovac, MD, tweeted: “It’s absolutely not a proper way to behave. Whether it’s behind the scenes or to your face. You can hear the arrogance from everyone including the moderator with his children comment. This is the true face of medicine.”

Jarey Wang, MD, PhD, however, liked the moderator’s input. “Love it. ‘Let’s all calm down children.’ Good for the moderator.”

Several of the physicians who commented thought that the issue should have been addressed at the time it happened. Don S. Dizon, MD, wrote, “Calling out microagressions as they occur is so important. And very difficult. Agree, the teachable moment must be met with bravery. But it should happen in real time too.”

After 2 days of bantering on Twitter, with the thread growing increasingly longer and with the vast majority of posts supporting Dr. Pal’s initial assessment, Dr. Higano finally entered the discussion and defended her comments: “What you do not know is that the questioner and I are good colleagues,” she tweeted. “I have been involved in two of his academic promotions. My main concern was his comment re: how the two trials could have ‘so different results with the same combination.’ I sought to rectify wrong message.”

There were no direct replies to Dr. Higano’s tweet.

Perhaps the line to draw under this affair is the tweet from Simon Kim, MD, MPH, who wrote: “We can do better!”

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

Correction, 2/24/22: Dr. Fred Saad's name was misstated in an earlier version of this article.

Twitter was all abuzz over an exchange that occurred Feb. 17 during the question-and-answer discussion that followed oral abstract presentations at the ASCO Genitourinary Cancers Symposium, held in San Francisco and also online. One of the panelists was accused of being less than professional in handling questions from the floor.

It began with a tweet from Sumanta Pal, MD, of the City of Hope, when he called out the behavior, although he did not identify the perpetrator.

“Yesterday we saw some reprehensible behavior emanating from the @ASCO #GU22 podium, with a well known investigator insulting (in a manner deeply imbued w microaggressions) an esteemed colleague at the mic. It’s a teachable moment & the lesson is simple: be kind to ur colleagues.”

It was not immediately clear what had occurred, and several people asked him to identify the people involved. One physician responded, “If it was bad enough to infer and share on Twitter, name the name.”

But even without details, the post provoked a reaction.

Erika Hamilton, MD, wrote, “I am not aware of this incident, but I always wonder ... if someone would do that from the podium, what would they/have they done and said when they didn’t think everyone was watching?”

Another tweet questioned why there were no codes of conduct in place, so that situations like this one wouldn’t happen.

“[It is] about time professional societies had codes of conduct in place for invited speakers, moderators of sessions etc,” wrote Deborah Verran, MD. “Then if it is breached the individual concerned is not invited back. This kind of incident also needs to be mentioned as part of the conference feedback process.”

As the number of clinicians chiming in increased, it soon became apparent that others were aware of the incident, and one posted a video clip, putting the mystery to rest.
 

Moderator quips, ‘Behave ... children’

The exchange occurred immediately following the oral abstract presentations on prostate cancer on Feb. 17. Two of these abstracts featured new data from large clinical trials investigating the use of PARP inhibitors in metastatic prostate cancer, which had slightly different results, leading to some debate. The PROpel trial with olaparib showed a benefit in all patients, irrespective of gene mutation status, but the MAGNITUDE trial with niraparib showed a benefit only in patients with gene alterations, and especially in those with BRCA1/2 mutations.

The invited discussant, Celestia Higano, MD, from the University of British Columbia, Vancouver, compared and contrasted the two trials and the differing results.

During the question-and-answer session that followed, Neeraj Agarwal, MD, from the Huntsman Cancer Institute, University of Utah, directed a question to Fred Saad, MD, who had presented the results of the PROpel trial.*

“As a practicing oncologist, I am very intrigued by the different results of the MAGNITUDE and PROpel trials. I am trying to figure out what do I do in my practice,” Dr. Agarwal began.

He continued on, explaining that he didn’t think that olaparib and niraparib were that different from one another for the two studies to have such differing results, when both of the drugs were given in combination with abiraterone.

The inclusion criteria for PROpel stipulated that patients undergo testing by ctDNA to determine if they were biomarker positive or not, but he pointed out that it is possible for testing to miss patients who might otherwise be positive for homologous recombination repair (HRR) gene alterations. He posed the question, could some of the patients deemed biomarker negative in fact have been positive but whose status was not detected by ctDNA testing?

At that point, Dr. Higano interrupted him before he had completed his question and asked, “Can I make a comment? Were you listening to my discussion?”

She then continued, pointing out that “you can’t talk about comparing olaparib and niraparib – these two trials had two very different populations.”

She emphasized that this was about the combinations in the populations being studied and not about olaparib and niraparib. “I clearly wasn’t very clear,” she said.

Dr. Agarwal then repeated that he wanted to know what to do with his patients and asked again about the accuracy of ctDNA testing.

“That’s a good question,” Dr. Higano said, “But the other comments you made weren’t.”

At that point, the moderator chimed in. “Let’s all calm down ... children.”

After a brief applause following the moderator’s comment, Dr. Saad then addressed the question.

When the video clip of this exchange was posted, a flood of tweets poured in, supporting Dr. Pal’s initial summation of the situation.

Alison Birtle, MD, tweeted, “I’m even more appalled having seen this exchange. Unacceptable. You don’t humiliate either the speaker or the delegate and the questions were entirely valid in my opinion. Basically what do I do tomorrow with these data so why ask were you listening. That’s just rude.”

Jason Kovac, MD, tweeted: “It’s absolutely not a proper way to behave. Whether it’s behind the scenes or to your face. You can hear the arrogance from everyone including the moderator with his children comment. This is the true face of medicine.”

Jarey Wang, MD, PhD, however, liked the moderator’s input. “Love it. ‘Let’s all calm down children.’ Good for the moderator.”

Several of the physicians who commented thought that the issue should have been addressed at the time it happened. Don S. Dizon, MD, wrote, “Calling out microagressions as they occur is so important. And very difficult. Agree, the teachable moment must be met with bravery. But it should happen in real time too.”

After 2 days of bantering on Twitter, with the thread growing increasingly longer and with the vast majority of posts supporting Dr. Pal’s initial assessment, Dr. Higano finally entered the discussion and defended her comments: “What you do not know is that the questioner and I are good colleagues,” she tweeted. “I have been involved in two of his academic promotions. My main concern was his comment re: how the two trials could have ‘so different results with the same combination.’ I sought to rectify wrong message.”

There were no direct replies to Dr. Higano’s tweet.

Perhaps the line to draw under this affair is the tweet from Simon Kim, MD, MPH, who wrote: “We can do better!”

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

Correction, 2/24/22: Dr. Fred Saad's name was misstated in an earlier version of this article.

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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

The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.

coldsnowstorm/iStock / Getty Images Plus

“Alcohol is a leading modifiable risk factor for cancer, yet most Americans are unaware that alcohol increases cancer risk,” write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.

“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.

The findings were published in the February issue of the American Journal of Preventive Medicine.

“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.

The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.

A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
 

Public support

The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.

As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:

• Banning outdoor alcohol-related advertising
• Requiring health warnings on alcohol beverage containers
• Requiring recommended drinking guidelines on alcoholic beverage containers

“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.

“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.

On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.

Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.

For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.

Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.

“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.

For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.

coldsnowstorm/iStock / Getty Images Plus

“Alcohol is a leading modifiable risk factor for cancer, yet most Americans are unaware that alcohol increases cancer risk,” write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.

“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.

The findings were published in the February issue of the American Journal of Preventive Medicine.

“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.

The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.

A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
 

Public support

The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.

As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:

• Banning outdoor alcohol-related advertising
• Requiring health warnings on alcohol beverage containers
• Requiring recommended drinking guidelines on alcoholic beverage containers

“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.

“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.

On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.

Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.

For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.

Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.

“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.

For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

The majority of Americans are not aware that alcohol consumption causes a variety of cancers and especially do not consider wine and beer to have a link with cancer, suggest the results from a national survey.

coldsnowstorm/iStock / Getty Images Plus

“Alcohol is a leading modifiable risk factor for cancer, yet most Americans are unaware that alcohol increases cancer risk,” write lead author Andrew Seidenberg, PhD, MPH, National Cancer Institute, Rockville, Md., and colleagues.

“Increasing awareness of the alcohol-cancer link, such as through multimedia campaigns and patient-provider communication, may be an important new strategy for health advocates working to implement preventive alcohol policies,” they add.

The findings were published in the February issue of the American Journal of Preventive Medicine.

“This is the first study to examine the relationship between alcohol control policy support and awareness of the alcohol-cancer link among a national U.S. sample,” the authors write.

The results show that there is some public support for the idea of adding written warnings about the alcohol-cancer risk to alcoholic beverages, which is something that a number of cancer organizations have been petitioning for.

A petition filed by the American Society of Clinical Oncology, the American Institute for Cancer Research, and Breast Cancer Prevention Partners, all in collaboration with several public health organizations, proposes labeling that would read: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

Such labeling has “the potential to save lives by ensuring that consumers have a more accurate understanding of the link between alcohol and cancer, which will empower them to better protect their health,” the groups said in the petition.
 

Public support

The findings come from an analysis of the 2020 Health Information National Trends Survey 5 Cycle 4. A total of 3,865 adults participated in the survey, approximately half of whom were nondrinkers.

As well as investigating how aware people were of the alcohol-cancer link, the investigators looked at how prevalent public support might be for the following three communication-focused alcohol policies:

• Banning outdoor alcohol-related advertising
• Requiring health warnings on alcohol beverage containers
• Requiring recommended drinking guidelines on alcoholic beverage containers

“Awareness of the alcohol-cancer link was measured separately for wine, beer, and liquor by asking: In your opinion, how much does drinking the following types of alcohol affect the risk of getting cancer?” the authors explain.

“Awareness of the alcohol-cancer link was low,” the investigators comment; only about one-third (31.8%) of participants were aware that alcohol increases the risk of cancer. The figures were even lower for individual beverage type, at 20.3% for wine, 24.9% for beer, and 31.2% for liquor. Furthermore, approximately half of participants responded with “don’t know” to the three awareness items, investigators noted.

On the other hand, more than half of the Americans surveyed supported adding both health warning labels (65.1%) and information on recommended drinking guidelines (63.9%) to alcoholic beverage containers. Support was lower (34.4% of respondents) for banning outdoor alcohol advertising.

Among Americans who were aware that alcohol increased cancer risk, support was also higher for all three policies.

For example, about 75% of respondents who were aware that alcohol increases cancer risk supported adding health warnings and drinking guidelines to beverage containers, compared with about half of Americans who felt that alcohol consumption had either no effect on or decreased cancer risk.

Even among those who were aware of the alcohol-cancer link, public support for outdoor advertising was not high (37.8%), but it was even lower (23.6%) among respondents who felt alcohol had no effect on or decreased the risk of cancer.

“Policy support was highest among nondrinkers, followed by drinkers, and was lowest among heavier drinkers,” the authors report.

For example, almost 43% of nondrinkers supported restrictions on outdoor alcohol advertising, compared with only about 28.6% of drinkers and 22% of heavier drinkers. More respondents supported adding health warning labels on alcoholic beverages – 70% of nondrinkers, 65% of drinkers, and 57% of heavier drinkers, investigators observe.

The study had no specific funding. The authors have disclosed no relevant financial relationships.

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

A number of clinical trials in breast cancer have opened in recent months. Maybe one of your patients could benefit from being enrolled.

• Menopausal women at moderate risk of developing breast cancer. A phase 2 study sponsored by the National Cancer Institute is seeking women aged 45-60 in late menopause or post menopause who are at “moderate” risk of developing breast cancer. Examples of criteria for moderate risk include prior proliferative disease on breast biopsy or having a first- or second-degree relative who developed breast cancer at aged 60 or younger. Researchers are looking for a signal that bazedoxifene plus conjugated estrogens (Duavee), a hot-flash therapy, could prevent breast cancer in at-risk people. Participants in the active-therapy group will receive once-daily oral medication for 6 months. The control patients will have the option of taking the medication after 6 months. The trial aims to enroll 120 participants. It began recruiting on Dec. 2, 2021, at the University of Kansas Medical Center; sites in California, Illinois, and Massachusetts are planned. The primary outcome is the change in fibroglandular volume. Overall survival (OS) and quality of life (QOL) will not be measured. More details at clinicaltrials.gov.

• Early high-risk nonmetastatic HER2+ breast cancer with no prior treatment. Adults with this type of breast cancer are invited to join a phase 3 trial of trastuzumab deruxtecan (T-DXd; Enhertu) as neoadjuvant therapy. T-DXd is currently approved for patients with advanced disease, so this study could lead to a new indication. Participants will receive standard intravenous regimens of either T-DXd monotherapy; T-DXd followed by paclitaxel (Taxol), trastuzumab (Herceptin), and pertuzumab (Perjeta), referred to as the THP regime; or doxorubicin plus cyclophosphamide followed by THP. The primary outcome is rate of pathologic complete response, and a secondary outcome is OS over approximately 5 years. QOL won’t be measured. The study opened on Oct. 25, 2021, and eventually hopes to recruit 624 participants in 19 countries and 15 U.S. states. More details at clinicaltrials.gov.

“[This is an] important early trial to move trastuzumab deruxtecan to early disease. If successful as monotherapy, this would be a big win for patients,” commented Kathy Miller, MD, professor of oncology and medicine at Indiana University, Indianapolis, a contributor to this news organization. She cautioned that monitoring rates of pneumonitis will be important in this curable setting.

• Locally advanced unresectable or metastatic HER2+ breast cancer with no prior tyrosine-kinase inhibitor therapy. Adult patients with these clinical features are eligible for a phase 3 study that is also testing a drug in an earlier setting than its current label – tucatinib (Tukysa) as first-line anti-HER2 therapy in advanced disease. Tucatinib was approved in April 2020 by the U.S. Food and Drug Administration as second-line therapy in such patients, so this study could also lead to a new indication. Participants in the experimental arm will receive tucatinib tablets twice daily and a combination of trastuzumab and pertuzumab intravenously or subcutaneously every 3 weeks for up to approximately 3 years. Patients in the control arm will take a placebo instead of tucatinib. Seven sites across Florida, Kentucky, Maryland, and South Carolina aim to start recruiting 650 participants on Feb. 28, 2022. The primary outcome is progression-free survival (PFS). OS and QoL will be tracked. More details at clinicaltrials.gov.

“Tucatinib has real activity,” commented Dr. Miller, adding that “we haven’t [yet] found the best way to exploit that activity for our patients.”

• Inoperable or metastatic HR+ HER2– breast cancer after one or two lines of systemic chemotherapy. Adults with this type of breast cancer are being recruited for a phase 3 study to compare datopotamab deruxtecan (Dato-DXd), an experimental antibody-drug conjugate (ADC), against a range of standard single-agent chemotherapies. Participants will receive either intravenous Dato-DXd or investigator’s choice of one of four chemotherapies: oral capecitabine (Xeloda), IV gemcitabine (Gemzar), IV eribulin (Halaven), or IV vinorelbine (Navelbine). The trial began recruiting for 700 participants at sites worldwide on Oct. 18, 2021. U.S. sites are in Michigan and California; trial centers in 15 other states are planned. Primary outcomes are OS over approximately 3.5 years and PFS over approximately 2 years. QOL is tracked. More details at clinicaltrials.gov.

Commenting on this trial, Dr. Miller said: “ADCs will play an expanded role in our management. This may be one of the first to move into the ER+ population.”

• Advanced ER+, HER2– breast cancer. Adult patients with this type of cancer can join a phase 3 trial testing oral imlunestrant, an experimental selective estrogen-receptor degrader (SERD), against standard endocrine therapy. For up to 3 years, people in the study will take either daily tablets of imlunestrant or once-daily pills of imlunestrant and another SERD, abemaciclib (Verzenio). A third group of participants will receive their investigator’s choice of either daily tablets of exemestane (Aromasin) or monthly intramuscular injections of fulvestrant (Faslodex). The study opened to 800 participants on Oct. 4, 2021, at sites in 11 U.S. states and worldwide. The primary outcome is PFS over approximately 3 years; 5-year OS is a secondary outcome. QOL is not assessed. More details at clinicaltrials.gov

Dr. Miller predicted that “oral SERDs will replace fulvestrant in the future: We already have positive phase 3 data with elacestrant.”

Dr. Miller has a regular column with this news organization, Miller on Oncology. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

A number of clinical trials in breast cancer have opened in recent months. Maybe one of your patients could benefit from being enrolled.

• Menopausal women at moderate risk of developing breast cancer. A phase 2 study sponsored by the National Cancer Institute is seeking women aged 45-60 in late menopause or post menopause who are at “moderate” risk of developing breast cancer. Examples of criteria for moderate risk include prior proliferative disease on breast biopsy or having a first- or second-degree relative who developed breast cancer at aged 60 or younger. Researchers are looking for a signal that bazedoxifene plus conjugated estrogens (Duavee), a hot-flash therapy, could prevent breast cancer in at-risk people. Participants in the active-therapy group will receive once-daily oral medication for 6 months. The control patients will have the option of taking the medication after 6 months. The trial aims to enroll 120 participants. It began recruiting on Dec. 2, 2021, at the University of Kansas Medical Center; sites in California, Illinois, and Massachusetts are planned. The primary outcome is the change in fibroglandular volume. Overall survival (OS) and quality of life (QOL) will not be measured. More details at clinicaltrials.gov.

• Early high-risk nonmetastatic HER2+ breast cancer with no prior treatment. Adults with this type of breast cancer are invited to join a phase 3 trial of trastuzumab deruxtecan (T-DXd; Enhertu) as neoadjuvant therapy. T-DXd is currently approved for patients with advanced disease, so this study could lead to a new indication. Participants will receive standard intravenous regimens of either T-DXd monotherapy; T-DXd followed by paclitaxel (Taxol), trastuzumab (Herceptin), and pertuzumab (Perjeta), referred to as the THP regime; or doxorubicin plus cyclophosphamide followed by THP. The primary outcome is rate of pathologic complete response, and a secondary outcome is OS over approximately 5 years. QOL won’t be measured. The study opened on Oct. 25, 2021, and eventually hopes to recruit 624 participants in 19 countries and 15 U.S. states. More details at clinicaltrials.gov.

“[This is an] important early trial to move trastuzumab deruxtecan to early disease. If successful as monotherapy, this would be a big win for patients,” commented Kathy Miller, MD, professor of oncology and medicine at Indiana University, Indianapolis, a contributor to this news organization. She cautioned that monitoring rates of pneumonitis will be important in this curable setting.

• Locally advanced unresectable or metastatic HER2+ breast cancer with no prior tyrosine-kinase inhibitor therapy. Adult patients with these clinical features are eligible for a phase 3 study that is also testing a drug in an earlier setting than its current label – tucatinib (Tukysa) as first-line anti-HER2 therapy in advanced disease. Tucatinib was approved in April 2020 by the U.S. Food and Drug Administration as second-line therapy in such patients, so this study could also lead to a new indication. Participants in the experimental arm will receive tucatinib tablets twice daily and a combination of trastuzumab and pertuzumab intravenously or subcutaneously every 3 weeks for up to approximately 3 years. Patients in the control arm will take a placebo instead of tucatinib. Seven sites across Florida, Kentucky, Maryland, and South Carolina aim to start recruiting 650 participants on Feb. 28, 2022. The primary outcome is progression-free survival (PFS). OS and QoL will be tracked. More details at clinicaltrials.gov.

“Tucatinib has real activity,” commented Dr. Miller, adding that “we haven’t [yet] found the best way to exploit that activity for our patients.”

• Inoperable or metastatic HR+ HER2– breast cancer after one or two lines of systemic chemotherapy. Adults with this type of breast cancer are being recruited for a phase 3 study to compare datopotamab deruxtecan (Dato-DXd), an experimental antibody-drug conjugate (ADC), against a range of standard single-agent chemotherapies. Participants will receive either intravenous Dato-DXd or investigator’s choice of one of four chemotherapies: oral capecitabine (Xeloda), IV gemcitabine (Gemzar), IV eribulin (Halaven), or IV vinorelbine (Navelbine). The trial began recruiting for 700 participants at sites worldwide on Oct. 18, 2021. U.S. sites are in Michigan and California; trial centers in 15 other states are planned. Primary outcomes are OS over approximately 3.5 years and PFS over approximately 2 years. QOL is tracked. More details at clinicaltrials.gov.

Commenting on this trial, Dr. Miller said: “ADCs will play an expanded role in our management. This may be one of the first to move into the ER+ population.”

• Advanced ER+, HER2– breast cancer. Adult patients with this type of cancer can join a phase 3 trial testing oral imlunestrant, an experimental selective estrogen-receptor degrader (SERD), against standard endocrine therapy. For up to 3 years, people in the study will take either daily tablets of imlunestrant or once-daily pills of imlunestrant and another SERD, abemaciclib (Verzenio). A third group of participants will receive their investigator’s choice of either daily tablets of exemestane (Aromasin) or monthly intramuscular injections of fulvestrant (Faslodex). The study opened to 800 participants on Oct. 4, 2021, at sites in 11 U.S. states and worldwide. The primary outcome is PFS over approximately 3 years; 5-year OS is a secondary outcome. QOL is not assessed. More details at clinicaltrials.gov

Dr. Miller predicted that “oral SERDs will replace fulvestrant in the future: We already have positive phase 3 data with elacestrant.”

Dr. Miller has a regular column with this news organization, Miller on Oncology. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

A number of clinical trials in breast cancer have opened in recent months. Maybe one of your patients could benefit from being enrolled.

• Menopausal women at moderate risk of developing breast cancer. A phase 2 study sponsored by the National Cancer Institute is seeking women aged 45-60 in late menopause or post menopause who are at “moderate” risk of developing breast cancer. Examples of criteria for moderate risk include prior proliferative disease on breast biopsy or having a first- or second-degree relative who developed breast cancer at aged 60 or younger. Researchers are looking for a signal that bazedoxifene plus conjugated estrogens (Duavee), a hot-flash therapy, could prevent breast cancer in at-risk people. Participants in the active-therapy group will receive once-daily oral medication for 6 months. The control patients will have the option of taking the medication after 6 months. The trial aims to enroll 120 participants. It began recruiting on Dec. 2, 2021, at the University of Kansas Medical Center; sites in California, Illinois, and Massachusetts are planned. The primary outcome is the change in fibroglandular volume. Overall survival (OS) and quality of life (QOL) will not be measured. More details at clinicaltrials.gov.

• Early high-risk nonmetastatic HER2+ breast cancer with no prior treatment. Adults with this type of breast cancer are invited to join a phase 3 trial of trastuzumab deruxtecan (T-DXd; Enhertu) as neoadjuvant therapy. T-DXd is currently approved for patients with advanced disease, so this study could lead to a new indication. Participants will receive standard intravenous regimens of either T-DXd monotherapy; T-DXd followed by paclitaxel (Taxol), trastuzumab (Herceptin), and pertuzumab (Perjeta), referred to as the THP regime; or doxorubicin plus cyclophosphamide followed by THP. The primary outcome is rate of pathologic complete response, and a secondary outcome is OS over approximately 5 years. QOL won’t be measured. The study opened on Oct. 25, 2021, and eventually hopes to recruit 624 participants in 19 countries and 15 U.S. states. More details at clinicaltrials.gov.

“[This is an] important early trial to move trastuzumab deruxtecan to early disease. If successful as monotherapy, this would be a big win for patients,” commented Kathy Miller, MD, professor of oncology and medicine at Indiana University, Indianapolis, a contributor to this news organization. She cautioned that monitoring rates of pneumonitis will be important in this curable setting.

• Locally advanced unresectable or metastatic HER2+ breast cancer with no prior tyrosine-kinase inhibitor therapy. Adult patients with these clinical features are eligible for a phase 3 study that is also testing a drug in an earlier setting than its current label – tucatinib (Tukysa) as first-line anti-HER2 therapy in advanced disease. Tucatinib was approved in April 2020 by the U.S. Food and Drug Administration as second-line therapy in such patients, so this study could also lead to a new indication. Participants in the experimental arm will receive tucatinib tablets twice daily and a combination of trastuzumab and pertuzumab intravenously or subcutaneously every 3 weeks for up to approximately 3 years. Patients in the control arm will take a placebo instead of tucatinib. Seven sites across Florida, Kentucky, Maryland, and South Carolina aim to start recruiting 650 participants on Feb. 28, 2022. The primary outcome is progression-free survival (PFS). OS and QoL will be tracked. More details at clinicaltrials.gov.

“Tucatinib has real activity,” commented Dr. Miller, adding that “we haven’t [yet] found the best way to exploit that activity for our patients.”

• Inoperable or metastatic HR+ HER2– breast cancer after one or two lines of systemic chemotherapy. Adults with this type of breast cancer are being recruited for a phase 3 study to compare datopotamab deruxtecan (Dato-DXd), an experimental antibody-drug conjugate (ADC), against a range of standard single-agent chemotherapies. Participants will receive either intravenous Dato-DXd or investigator’s choice of one of four chemotherapies: oral capecitabine (Xeloda), IV gemcitabine (Gemzar), IV eribulin (Halaven), or IV vinorelbine (Navelbine). The trial began recruiting for 700 participants at sites worldwide on Oct. 18, 2021. U.S. sites are in Michigan and California; trial centers in 15 other states are planned. Primary outcomes are OS over approximately 3.5 years and PFS over approximately 2 years. QOL is tracked. More details at clinicaltrials.gov.

Commenting on this trial, Dr. Miller said: “ADCs will play an expanded role in our management. This may be one of the first to move into the ER+ population.”

• Advanced ER+, HER2– breast cancer. Adult patients with this type of cancer can join a phase 3 trial testing oral imlunestrant, an experimental selective estrogen-receptor degrader (SERD), against standard endocrine therapy. For up to 3 years, people in the study will take either daily tablets of imlunestrant or once-daily pills of imlunestrant and another SERD, abemaciclib (Verzenio). A third group of participants will receive their investigator’s choice of either daily tablets of exemestane (Aromasin) or monthly intramuscular injections of fulvestrant (Faslodex). The study opened to 800 participants on Oct. 4, 2021, at sites in 11 U.S. states and worldwide. The primary outcome is PFS over approximately 3 years; 5-year OS is a secondary outcome. QOL is not assessed. More details at clinicaltrials.gov

Dr. Miller predicted that “oral SERDs will replace fulvestrant in the future: We already have positive phase 3 data with elacestrant.”

Dr. Miller has a regular column with this news organization, Miller on Oncology. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Patients with stage II to IVB nasopharyngeal carcinoma who were treated with nedaplatin-based concurrent chemoradiotherapy, achieved 5-year survival rates comparable to those of patients treated with cisplatin chemoradiotherapy, but with fewer toxic effects, shows a study in JAMA Network Open.

The findings confirm that nedaplatin-based chemoradiotherapy could be considered as an alternative to cisplatin for stage II to IVB nasopharyngeal carcinoma, wrote authors who were led by Lin-Quan Tang, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, China.

While the National Comprehensive Cancer Network recommends radiotherapy administered concurrently with 100 mg/m² of cisplatin every 3 weeks for patients with stage II to IVB nasopharyngeal carcinoma, the addition of cisplatin-based chemotherapy to radiotherapy increases the frequency of treatment-related toxic effects. They include severe gastrointestinal responses, hearing deficits, renal toxic effects, and neurotoxic effects, decreasing treatment adherence and patient quality of life. An antitumor drug with similar therapeutic efficacy to cisplatin but with reduced adverse effects is needed urgently, authors wrote.

The cisplatin analogue nedaplatin, designed to decrease the nephrotoxic and gastrointestinal toxic effects seen with cisplatin, has antitumor mechanisms and efficacy similar to cisplatin. It has demonstrated effectiveness and tolerability in various malignant tumors, and has, in vitro, shown potential as a radiosensitizing agent with nasopharyngeal carcinoma and cervical squamous cell carcinoma cells.

In the initial 2-year results of the phase 3 randomized trial in this population of patients with stage II to IVB nasopharyngeal carcinoma, nedaplatin-based concurrent chemoradiotherapy was noninferior to cisplatin-based concurrent chemoradiotherapy with differences of 1.9% and 1.0% (P = .005 and P = .002), in the intention-to-treat and per-protocol analyses of progression-free survival, respectively. Patients (n = 402) were randomly assigned (1:1) to receive nedaplatin (100 mg/m²)– or cisplatin (100 mg/m²)–based chemotherapy every 3 weeks for three cycles concurrently with intensity-modulated radiotherapy. Information on long-term follow-up and late toxic effects was limited.

In the current analysis of 402 patients (about 25% female, median age 44.5 years), the intention-to-treat 5-year progression-free survival rate was 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for the nedaplatin group, with a difference of 1.6% (95% CI, −6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs. 88.8%; P = .63), distant metastasis–free survival (85.9% vs. 90.4%, P = .17), and locoregional relapse–free survival (92.6% vs. 89.6%; P = .17) rates.

The incidence of grade 3 and 4 auditory toxic effects was higher in the cisplatin group than in the nedaplatin group (35 [17.7%] vs. 21 [10.5%], P = .04). Also, the cumulative incidence of grade 3-4 auditory toxic effects was higher in the cisplatin group versus patients in the nedaplatin group (19.9% vs. 12.0%; P = .42). The odds ratio, in a post hoc regression analysis, for auditory toxic effects was 0.51 (0.51; 95% CI, 0.28-0.93; P = .03) for patients in the nedaplatin group.

The findings, the authors concluded, confirm that nedaplatin-based concurrent chemoradiotherapy could be an alternative to cisplatin-based concurrent chemoradiotherapy as doublet therapy for II to IVB nasopharyngeal carcinoma. The potential of nedaplatin in combination drug chemotherapy for nasopharyngeal carcinoma in the induction or adjuvant phase needs to be explored in further investigations, the authors added.

The study was funded by multiple grants; the study investigator reported no conflicts of interest.

Patients with stage II to IVB nasopharyngeal carcinoma who were treated with nedaplatin-based concurrent chemoradiotherapy, achieved 5-year survival rates comparable to those of patients treated with cisplatin chemoradiotherapy, but with fewer toxic effects, shows a study in JAMA Network Open.

The findings confirm that nedaplatin-based chemoradiotherapy could be considered as an alternative to cisplatin for stage II to IVB nasopharyngeal carcinoma, wrote authors who were led by Lin-Quan Tang, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, China.

While the National Comprehensive Cancer Network recommends radiotherapy administered concurrently with 100 mg/m² of cisplatin every 3 weeks for patients with stage II to IVB nasopharyngeal carcinoma, the addition of cisplatin-based chemotherapy to radiotherapy increases the frequency of treatment-related toxic effects. They include severe gastrointestinal responses, hearing deficits, renal toxic effects, and neurotoxic effects, decreasing treatment adherence and patient quality of life. An antitumor drug with similar therapeutic efficacy to cisplatin but with reduced adverse effects is needed urgently, authors wrote.

The cisplatin analogue nedaplatin, designed to decrease the nephrotoxic and gastrointestinal toxic effects seen with cisplatin, has antitumor mechanisms and efficacy similar to cisplatin. It has demonstrated effectiveness and tolerability in various malignant tumors, and has, in vitro, shown potential as a radiosensitizing agent with nasopharyngeal carcinoma and cervical squamous cell carcinoma cells.

In the initial 2-year results of the phase 3 randomized trial in this population of patients with stage II to IVB nasopharyngeal carcinoma, nedaplatin-based concurrent chemoradiotherapy was noninferior to cisplatin-based concurrent chemoradiotherapy with differences of 1.9% and 1.0% (P = .005 and P = .002), in the intention-to-treat and per-protocol analyses of progression-free survival, respectively. Patients (n = 402) were randomly assigned (1:1) to receive nedaplatin (100 mg/m²)– or cisplatin (100 mg/m²)–based chemotherapy every 3 weeks for three cycles concurrently with intensity-modulated radiotherapy. Information on long-term follow-up and late toxic effects was limited.

In the current analysis of 402 patients (about 25% female, median age 44.5 years), the intention-to-treat 5-year progression-free survival rate was 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for the nedaplatin group, with a difference of 1.6% (95% CI, −6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs. 88.8%; P = .63), distant metastasis–free survival (85.9% vs. 90.4%, P = .17), and locoregional relapse–free survival (92.6% vs. 89.6%; P = .17) rates.

The incidence of grade 3 and 4 auditory toxic effects was higher in the cisplatin group than in the nedaplatin group (35 [17.7%] vs. 21 [10.5%], P = .04). Also, the cumulative incidence of grade 3-4 auditory toxic effects was higher in the cisplatin group versus patients in the nedaplatin group (19.9% vs. 12.0%; P = .42). The odds ratio, in a post hoc regression analysis, for auditory toxic effects was 0.51 (0.51; 95% CI, 0.28-0.93; P = .03) for patients in the nedaplatin group.

The findings, the authors concluded, confirm that nedaplatin-based concurrent chemoradiotherapy could be an alternative to cisplatin-based concurrent chemoradiotherapy as doublet therapy for II to IVB nasopharyngeal carcinoma. The potential of nedaplatin in combination drug chemotherapy for nasopharyngeal carcinoma in the induction or adjuvant phase needs to be explored in further investigations, the authors added.

The study was funded by multiple grants; the study investigator reported no conflicts of interest.

Patients with stage II to IVB nasopharyngeal carcinoma who were treated with nedaplatin-based concurrent chemoradiotherapy, achieved 5-year survival rates comparable to those of patients treated with cisplatin chemoradiotherapy, but with fewer toxic effects, shows a study in JAMA Network Open.

The findings confirm that nedaplatin-based chemoradiotherapy could be considered as an alternative to cisplatin for stage II to IVB nasopharyngeal carcinoma, wrote authors who were led by Lin-Quan Tang, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, China.

While the National Comprehensive Cancer Network recommends radiotherapy administered concurrently with 100 mg/m² of cisplatin every 3 weeks for patients with stage II to IVB nasopharyngeal carcinoma, the addition of cisplatin-based chemotherapy to radiotherapy increases the frequency of treatment-related toxic effects. They include severe gastrointestinal responses, hearing deficits, renal toxic effects, and neurotoxic effects, decreasing treatment adherence and patient quality of life. An antitumor drug with similar therapeutic efficacy to cisplatin but with reduced adverse effects is needed urgently, authors wrote.

The cisplatin analogue nedaplatin, designed to decrease the nephrotoxic and gastrointestinal toxic effects seen with cisplatin, has antitumor mechanisms and efficacy similar to cisplatin. It has demonstrated effectiveness and tolerability in various malignant tumors, and has, in vitro, shown potential as a radiosensitizing agent with nasopharyngeal carcinoma and cervical squamous cell carcinoma cells.

In the initial 2-year results of the phase 3 randomized trial in this population of patients with stage II to IVB nasopharyngeal carcinoma, nedaplatin-based concurrent chemoradiotherapy was noninferior to cisplatin-based concurrent chemoradiotherapy with differences of 1.9% and 1.0% (P = .005 and P = .002), in the intention-to-treat and per-protocol analyses of progression-free survival, respectively. Patients (n = 402) were randomly assigned (1:1) to receive nedaplatin (100 mg/m²)– or cisplatin (100 mg/m²)–based chemotherapy every 3 weeks for three cycles concurrently with intensity-modulated radiotherapy. Information on long-term follow-up and late toxic effects was limited.

In the current analysis of 402 patients (about 25% female, median age 44.5 years), the intention-to-treat 5-year progression-free survival rate was 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for the nedaplatin group, with a difference of 1.6% (95% CI, −6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs. 88.8%; P = .63), distant metastasis–free survival (85.9% vs. 90.4%, P = .17), and locoregional relapse–free survival (92.6% vs. 89.6%; P = .17) rates.

The incidence of grade 3 and 4 auditory toxic effects was higher in the cisplatin group than in the nedaplatin group (35 [17.7%] vs. 21 [10.5%], P = .04). Also, the cumulative incidence of grade 3-4 auditory toxic effects was higher in the cisplatin group versus patients in the nedaplatin group (19.9% vs. 12.0%; P = .42). The odds ratio, in a post hoc regression analysis, for auditory toxic effects was 0.51 (0.51; 95% CI, 0.28-0.93; P = .03) for patients in the nedaplatin group.

The findings, the authors concluded, confirm that nedaplatin-based concurrent chemoradiotherapy could be an alternative to cisplatin-based concurrent chemoradiotherapy as doublet therapy for II to IVB nasopharyngeal carcinoma. The potential of nedaplatin in combination drug chemotherapy for nasopharyngeal carcinoma in the induction or adjuvant phase needs to be explored in further investigations, the authors added.

The study was funded by multiple grants; the study investigator reported no conflicts of interest.

Women are at higher risk of severe adverse events (AEs) from cancer therapy than men, and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.

The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.

The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.

Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.

The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.

The article was published online on Feb. 4 in the Journal of Clinical Oncology.

“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.

A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.

Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.

Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
 

Study details

The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.

Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.

Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.

After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.

Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.

As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.

The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.

However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.

The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.

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

Women are at higher risk of severe adverse events (AEs) from cancer therapy than men, and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.

The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.

The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.

Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.

The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.

The article was published online on Feb. 4 in the Journal of Clinical Oncology.

“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.

A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.

Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.

Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
 

Study details

The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.

Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.

Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.

After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.

Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.

As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.

The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.

However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.

The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.

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

Women are at higher risk of severe adverse events (AEs) from cancer therapy than men, and this is seen with chemotherapy, targeted agents, and especially with immunotherapy.

The finding comes from a review of more than 23,000 participants across 202 trials of various cancers (excluding sex-related cancers) that has been conducted over the past 40 years.

The investigators found a 34% increased risk of severe AEs among women, compared with men, climbing to a 49% higher risk with immunotherapy.

Women had a substantially greater risk of severe symptomatic AEs, including with immune checkpoint inhibitors and targeted tyrosine kinase inhibitors, and were more likely to experience severe hematologic AEs with chemotherapy and immunotherapy.

The particularly large sex differences with immunotherapy suggest “that studying AEs from these agents is a priority,” the investigators comment.

The article was published online on Feb. 4 in the Journal of Clinical Oncology.

“It has been understood that women have more toxicity from chemotherapy than men, but almost no research has aimed to understand whether that pattern held for novel treatments like immunotherapy or targeted therapies. We found similar large differences, especially for immune treatments,” said lead investigator Joseph Unger, PhD, a biostatistician and health services researcher at the Fred Hutchinson Cancer Research Center, Seattle, in an institutional press release.

A “better understanding of the nature of the underlying mechanisms could potentially lead to interventions or delivery modifications to reduce toxicity in women,” the investigators comment in their article.

Among a sea of possible explanations for the finding, there could be differences in how men and women metabolize cancer therapies or differences in how they perceive symptoms. Women may also receive relatively higher doses because of their body size or have higher adherence to treatment.

Whatever the case, as cancer treatment becomes increasingly individualized, “sex may be an important consideration,” Dr. Unger said.
 

Study details

The study involved 8,838 women and 14,458 men across the trials, which were phase 2 or 3 investigations conducted by the SWOG Cancer Research Network from 1980 to 2019. Trials including sex-related cancers were excluded. In the trials included in the review, the most common cancers were gastrointestinal and lung, followed by leukemia.

Seventy-five percent of the subjects received chemotherapy, and the rest received either targeted therapy or immunotherapy.

Two-thirds of the subjects had at least one grade 3 or higher AE; women had a 25% higher risk than men of having AEs of grade 5 or higher.

After adjusting for age, race, disease prognosis, and other factors, women were at increased risk of severe symptomatic AEs, such as nausea and pain, across all treatment lines and especially with immunotherapy, for which reports of symptomatic AEs were 66% higher.

Women also had a higher risk of symptomatic gastrointestinal AEs with all three treatments and a higher risk of sleep-related AEs with chemotherapy and immunotherapy, which “could be a function of hormonal effects interacting with cancer treatment,” the investigators said.

As for readily measurable AEs, women were at higher risk than men for objective hematologic AEs with chemotherapy, immunotherapy, and targeted therapy. There were no statistically significant sex differences in the risk of nonhematologic objective AEs.

The team notes that increased toxicity among women has been associated with improved survival, which may give AEs more time to develop. Higher rates of AEs might also signal increased delivery or efficacy of cancer treatments.

However, a previous study found that men may have a better response to immunotherapy than women. Immune checkpoint inhibitors were twice as effective as standard cancer therapies in the treatment of men with advanced solid tumors compared to their female counterparts, concluded a team that carried out a meta-analysis of 20 randomized controlled trials involving more than 11,351 patients.

The study was funded by the National Cancer Institute and others. Dr. Unger has disclosed no relevant financial relationships. Several coauthors have reported ties to a handful of companies, including Johnson & Johnson and Seattle Genetics. One is an employee of AIM Specialty Health.

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

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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

The Centers for Medicare & Medicaid Services (CMS) will expand eligibility guidelines for lung cancer screening with low-dose computed tomography for Medicare recipients.

According to the final decision, announced February 10, CMS will lower the age for screening from 55 to 50 years up to 77 years and reduce criteria for tobacco smoking history from at least 30 pack-years to 20 pack-years. The expanded Medicare recommendation will address racial disparities associated with lung cancer, given evidence that one third of Black patients are diagnosed with lung cancer before age 55.

The updated CMS guidelines align closely with recommendations made by the U.S. Preventive Services Task Force (USPSTF) in March 2021. The USPSTF expanded its guidelines for screening to include individuals ages 50 to 80 years, as well as those who have a 20–pack-year smoking history and who currently smoke or have quit within the past 15 years.

Overall, the expanded guidelines will nearly double the number of individuals who are eligible for screening and have the potential to save significantly more lives by identifying cancers at an earlier, more treatable stage.

“Expanding coverage broadens access for lung cancer screening to at-risk populations,” said Lee Felisher, MD, CMS chief medical officer and director of the Center for Clinical Standards and Quality, in a statement. “Today’s decision not only expands access to quality care but is also critical to improving health outcomes for people by helping to detect lung cancer earlier.”

CMS’s decision also simplifies requirements for counseling and shared decision-making visits and removes an initial requirement for the reading radiologist to document participation in continuing medical education, which will reduce administrative burden. CMS also added a requirement back to the National Coverage Determination criteria that requires radiology imaging facilities to use a standardized lung nodule identification, classification, and reporting system.

The American Lung Association applauds the decision to update eligibility.

“[The] announcement from CMS will give more people enrolled in Medicare access to lifesaving lung cancer screening. Screening for individuals at high risk is the only tool to catch this disease early when it is more curable,” Harold Wimmer, president and CEO of the American Lung Association, said in a statement. “Unfortunately, only 5.7% of people who are eligible have been screened, so it’s important that we talk with our friends and family who are at high risk about getting screened.”

While access to screening will significantly increase, the American Lung Association recommends CMS go a step further and expand eligibility to individuals up to 80 years of age, as the USPSTF recommendations do, as well as remove the recommendation that individuals cease screening once they have stopped smoking for 15 years.

Given the new guidelines, most private insurance plans will need to update screening coverage policies to reflect the updated guidelines for plan years beginning after March 31.

To read the final decision, visit the CMS website.

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