Sharon Worcester

Among cancer patients with solid tumors, the response to the COVID-19 vaccine 6 months after receiving a second dose was as good as that of the general population, according to new findings from a case-control study.

The BNT162b2, or Pfizer-BioNTech, vaccine (Comirnaty) was previously shown to have good short-term efficacy, immunogenicity, and safety in cancer patients with solid tumors, but little is known about longer-term efficacy in this population, say the investigators.

They assessed responses 6 months after a second dose of the vaccine.

Serologic tests showed that 122 of 154 patients with solid tumors who were actively undergoing cancer treatment (79%) and 114 of 135 age-matched health care workers who served as control persons (84%) were seropositive at 6 months (P = .32).

Most (81%) of the patients with cancer who were seronegative were receiving chemotherapy, the researchers report.

One case of severe COVID-19 that required hospitalization occurred among the solid-tumor group; none occurred among the control persons, they also note.

The findings were published online on Sept. 2 in Cancer Discovery.

“In our study we saw that in all outcomes, including immunogenicity, infectivity rate throughout the 6-month period, and safety, patients with solid tumors depicted a similar trend as the general population,” commented lead author Irit Ben-Aharon, MD, PhD, director of the division of oncology at Rambam Health Care Campus, Haifa, Israel, in an American Association for Cancer Research press statement.

However, she and her coauthors stressed the importance of continuing to follow guidance, such as social distancing and mask wearing, for reducing COVID-19 transmission. “Due to uncertainty of the extended efficacy of the vaccine in the general population and recent reports on rising infection rates among vaccinated individuals, adherence to health care risk reduction recommendations is cardinal,” they write.

The mean age of the control persons in the study was 63 years, and the mean age of the case patients was 66 years. The most common cancers were gastrointestinal (36%), lung (23%), breast (17%), and genitourinary (11%). Treatment protocols included chemotherapy (62%), biological agents (36%), and immunotherapy (30%). Some patients received more than one type of treatment.

All of the reported adverse effects associated with vaccination had resolved at the time of follow-up.

These data can “help inform recommendations surrounding the prioritization of different groups for booster vaccines,” Dr. Ben-Aharon adds.

In fact, recently updated guidelines from the National Comprehensive Cancer Network state that cancer patients with solid tumors who are receiving treatment within 1 year of their initial vaccine dose should be prioritized for a booster vaccine.

The study was partially supported by the Israel Cancer Research Fund. Serologic testing of the control cohort was supported by the Ministry of Health, Israel. The authors have disclosed no relevant financial relationships.

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

Among cancer patients with solid tumors, the response to the COVID-19 vaccine 6 months after receiving a second dose was as good as that of the general population, according to new findings from a case-control study.

The BNT162b2, or Pfizer-BioNTech, vaccine (Comirnaty) was previously shown to have good short-term efficacy, immunogenicity, and safety in cancer patients with solid tumors, but little is known about longer-term efficacy in this population, say the investigators.

They assessed responses 6 months after a second dose of the vaccine.

Serologic tests showed that 122 of 154 patients with solid tumors who were actively undergoing cancer treatment (79%) and 114 of 135 age-matched health care workers who served as control persons (84%) were seropositive at 6 months (P = .32).

Most (81%) of the patients with cancer who were seronegative were receiving chemotherapy, the researchers report.

One case of severe COVID-19 that required hospitalization occurred among the solid-tumor group; none occurred among the control persons, they also note.

The findings were published online on Sept. 2 in Cancer Discovery.

“In our study we saw that in all outcomes, including immunogenicity, infectivity rate throughout the 6-month period, and safety, patients with solid tumors depicted a similar trend as the general population,” commented lead author Irit Ben-Aharon, MD, PhD, director of the division of oncology at Rambam Health Care Campus, Haifa, Israel, in an American Association for Cancer Research press statement.

However, she and her coauthors stressed the importance of continuing to follow guidance, such as social distancing and mask wearing, for reducing COVID-19 transmission. “Due to uncertainty of the extended efficacy of the vaccine in the general population and recent reports on rising infection rates among vaccinated individuals, adherence to health care risk reduction recommendations is cardinal,” they write.

The mean age of the control persons in the study was 63 years, and the mean age of the case patients was 66 years. The most common cancers were gastrointestinal (36%), lung (23%), breast (17%), and genitourinary (11%). Treatment protocols included chemotherapy (62%), biological agents (36%), and immunotherapy (30%). Some patients received more than one type of treatment.

All of the reported adverse effects associated with vaccination had resolved at the time of follow-up.

These data can “help inform recommendations surrounding the prioritization of different groups for booster vaccines,” Dr. Ben-Aharon adds.

In fact, recently updated guidelines from the National Comprehensive Cancer Network state that cancer patients with solid tumors who are receiving treatment within 1 year of their initial vaccine dose should be prioritized for a booster vaccine.

The study was partially supported by the Israel Cancer Research Fund. Serologic testing of the control cohort was supported by the Ministry of Health, Israel. The authors have disclosed no relevant financial relationships.

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

Among cancer patients with solid tumors, the response to the COVID-19 vaccine 6 months after receiving a second dose was as good as that of the general population, according to new findings from a case-control study.

The BNT162b2, or Pfizer-BioNTech, vaccine (Comirnaty) was previously shown to have good short-term efficacy, immunogenicity, and safety in cancer patients with solid tumors, but little is known about longer-term efficacy in this population, say the investigators.

They assessed responses 6 months after a second dose of the vaccine.

Serologic tests showed that 122 of 154 patients with solid tumors who were actively undergoing cancer treatment (79%) and 114 of 135 age-matched health care workers who served as control persons (84%) were seropositive at 6 months (P = .32).

Most (81%) of the patients with cancer who were seronegative were receiving chemotherapy, the researchers report.

One case of severe COVID-19 that required hospitalization occurred among the solid-tumor group; none occurred among the control persons, they also note.

The findings were published online on Sept. 2 in Cancer Discovery.

“In our study we saw that in all outcomes, including immunogenicity, infectivity rate throughout the 6-month period, and safety, patients with solid tumors depicted a similar trend as the general population,” commented lead author Irit Ben-Aharon, MD, PhD, director of the division of oncology at Rambam Health Care Campus, Haifa, Israel, in an American Association for Cancer Research press statement.

However, she and her coauthors stressed the importance of continuing to follow guidance, such as social distancing and mask wearing, for reducing COVID-19 transmission. “Due to uncertainty of the extended efficacy of the vaccine in the general population and recent reports on rising infection rates among vaccinated individuals, adherence to health care risk reduction recommendations is cardinal,” they write.

The mean age of the control persons in the study was 63 years, and the mean age of the case patients was 66 years. The most common cancers were gastrointestinal (36%), lung (23%), breast (17%), and genitourinary (11%). Treatment protocols included chemotherapy (62%), biological agents (36%), and immunotherapy (30%). Some patients received more than one type of treatment.

All of the reported adverse effects associated with vaccination had resolved at the time of follow-up.

These data can “help inform recommendations surrounding the prioritization of different groups for booster vaccines,” Dr. Ben-Aharon adds.

In fact, recently updated guidelines from the National Comprehensive Cancer Network state that cancer patients with solid tumors who are receiving treatment within 1 year of their initial vaccine dose should be prioritized for a booster vaccine.

The study was partially supported by the Israel Cancer Research Fund. Serologic testing of the control cohort was supported by the Ministry of Health, Israel. The authors have disclosed no relevant financial relationships.

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

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

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

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

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

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

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

The U.S. Food and Drug Administration has issued a safety alert regarding an increased risk of death associated with Pepaxto (melphalan flufenamide) used in patients with multiple myeloma participating in the ongoing OCEAN clinical trial.

The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.

Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.

The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.

Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”

The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
 

Accelerated approval data

Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.

Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
 

Confirmatory trial data

The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.

The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.

“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.

The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.

Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.

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

The U.S. Food and Drug Administration has issued a safety alert regarding an increased risk of death associated with Pepaxto (melphalan flufenamide) used in patients with multiple myeloma participating in the ongoing OCEAN clinical trial.

The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.

Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.

The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.

Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”

The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
 

Accelerated approval data

Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.

Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
 

Confirmatory trial data

The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.

The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.

“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.

The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.

Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.

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

The U.S. Food and Drug Administration has issued a safety alert regarding an increased risk of death associated with Pepaxto (melphalan flufenamide) used in patients with multiple myeloma participating in the ongoing OCEAN clinical trial.

The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.

Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.

The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.

Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”

The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
 

Accelerated approval data

Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.

Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.

Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
 

Confirmatory trial data

The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.

The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.

“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.

The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.

Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.

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

Many of the changes to cancer clinical trials forced through by the COVID-19 pandemic should remain, as they have made trials “more patient centered and efficient,” according to a group of thought leaders in oncology.

Among the potential improvements were more efficient study enrollment through secure electronic platforms, direct shipment of oral drugs to patients, remote assessment of adverse events, and streamlined data collection.

These changes should be implemented on a permanent basis, the group argues in a commentary published online July 21, 2021, in Cancer Discovery, a journal of the American Association for Cancer Research.

“The ability to distribute oral investigational drugs by mail to patients at their home has probably been the single most impactful change to clinical trial conduct, linked with virtual visits with patients to assess side effects and symptoms,” commented lead author Keith Flaherty, MD, who is director of clinical research at Massachusetts General Hospital, a professor at Harvard Medical School, Boston, and a member of the AACR board of directors.

“This has made it more feasible for patients for whom participation in clinical trials poses a disruption of their ability to work or provide care for family members to participate in trials,” he added in a press statement issued by the AACR.
 

Pandemic halted many clinical trials

A survey of cancer programs in early 2020 showed that nearly 60% halted screening and/or enrollment for at least some trials because of COVID-19.

“In the spring of 2020, clinical trial conduct halted and then restarted focusing on the bare minimum procedures that first allowed patients continued access to their experimental therapies, and then allowed clinical trial sites and sponsors to collect information on the effects of the therapies,” the authors said.

“The COVID-19–induced changes to clinical trials were a big challenge, probably the largest change in clinical trial conduct since the start of modern oncology clinical testing,” they commented.

“But it also represents an opportunity to rethink the key aspects of clinical trial conduct that are strictly necessary to reach the goal of testing the effectiveness of cancer therapies, and which others are dispensable or provide only minor additional contributions,” they added.

As previously reported at the time by this news organization, efforts to find alternative approaches to conducting trials amid the pandemic led to the emergence of a few “silver linings.”

Key adaptations made to clinical trials and highlighted by the authors include:

• Uptake of remote consenting and telemedicine
• Use of alternative laboratories and imaging centers
• Delivery or administration of investigational drugs at patients’ homes or local clinics
• Commercial attainment of study drugs already approved for other indications

Indeed, the restrictions encountered during the pandemic underscore the importance of designing patient-centered trials versus study site–centered trials, added Antoni Ribas, MD, commentary coauthor and immediate past president of the AACR.

Many of the changes implemented during the pandemic could help increase access for patients living in underserved communities who are underrepresented in clinical trials, he explained.
 

Harnessing the lessons learned

The authors also recommended the following additional adaptations, which they believe will enhance efficiency and further expand access to clinical trials:

• Incorporating patient-reported outcomes and alternative endpoints in efficacy assessments
• Aiming for 100% remote drug infusions and monitoring
• Increasing funding for clinical trials conducted in underserved communities
• Expanding clinical trial eligibility to include patients with a wide range of comorbidities
• Reducing collection of low-grade adverse events and allowing minor protocol deviations

The group’s recommendations are based on discussions by the AACR COVID-19 and Cancer Task Force, in which they participated.

The American Society of Clinical Oncology is also working to leverage pandemic-related lessons to streamline care and trial planning.

ASCO’s “Road to Recovery” recommendations, published in December 2020, aim to “ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality,” the authors explained.

Dr. Flaherty and colleagues further underscore the importance of focusing on improvements going forward.

“Guided by lessons learned, many of the remote assessments and trial efficiencies deployed during the pandemic can be preserved and improved upon. We strongly encourage use of these streamlined procedures where appropriate in future prospectively designed cancer clinical trials,” they wrote.

Dr. Flaherty reported receiving personal fees from numerous pharmaceutical companies. Dr. Ribas reported receiving grants from Agilent and Bristol Myers Squibb.

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

Many of the changes to cancer clinical trials forced through by the COVID-19 pandemic should remain, as they have made trials “more patient centered and efficient,” according to a group of thought leaders in oncology.

Among the potential improvements were more efficient study enrollment through secure electronic platforms, direct shipment of oral drugs to patients, remote assessment of adverse events, and streamlined data collection.

These changes should be implemented on a permanent basis, the group argues in a commentary published online July 21, 2021, in Cancer Discovery, a journal of the American Association for Cancer Research.

“The ability to distribute oral investigational drugs by mail to patients at their home has probably been the single most impactful change to clinical trial conduct, linked with virtual visits with patients to assess side effects and symptoms,” commented lead author Keith Flaherty, MD, who is director of clinical research at Massachusetts General Hospital, a professor at Harvard Medical School, Boston, and a member of the AACR board of directors.

“This has made it more feasible for patients for whom participation in clinical trials poses a disruption of their ability to work or provide care for family members to participate in trials,” he added in a press statement issued by the AACR.
 

Pandemic halted many clinical trials

A survey of cancer programs in early 2020 showed that nearly 60% halted screening and/or enrollment for at least some trials because of COVID-19.

“In the spring of 2020, clinical trial conduct halted and then restarted focusing on the bare minimum procedures that first allowed patients continued access to their experimental therapies, and then allowed clinical trial sites and sponsors to collect information on the effects of the therapies,” the authors said.

“The COVID-19–induced changes to clinical trials were a big challenge, probably the largest change in clinical trial conduct since the start of modern oncology clinical testing,” they commented.

“But it also represents an opportunity to rethink the key aspects of clinical trial conduct that are strictly necessary to reach the goal of testing the effectiveness of cancer therapies, and which others are dispensable or provide only minor additional contributions,” they added.

As previously reported at the time by this news organization, efforts to find alternative approaches to conducting trials amid the pandemic led to the emergence of a few “silver linings.”

Key adaptations made to clinical trials and highlighted by the authors include:

• Uptake of remote consenting and telemedicine
• Use of alternative laboratories and imaging centers
• Delivery or administration of investigational drugs at patients’ homes or local clinics
• Commercial attainment of study drugs already approved for other indications

Indeed, the restrictions encountered during the pandemic underscore the importance of designing patient-centered trials versus study site–centered trials, added Antoni Ribas, MD, commentary coauthor and immediate past president of the AACR.

Many of the changes implemented during the pandemic could help increase access for patients living in underserved communities who are underrepresented in clinical trials, he explained.
 

Harnessing the lessons learned

The authors also recommended the following additional adaptations, which they believe will enhance efficiency and further expand access to clinical trials:

• Incorporating patient-reported outcomes and alternative endpoints in efficacy assessments
• Aiming for 100% remote drug infusions and monitoring
• Increasing funding for clinical trials conducted in underserved communities
• Expanding clinical trial eligibility to include patients with a wide range of comorbidities
• Reducing collection of low-grade adverse events and allowing minor protocol deviations

The group’s recommendations are based on discussions by the AACR COVID-19 and Cancer Task Force, in which they participated.

The American Society of Clinical Oncology is also working to leverage pandemic-related lessons to streamline care and trial planning.

ASCO’s “Road to Recovery” recommendations, published in December 2020, aim to “ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality,” the authors explained.

Dr. Flaherty and colleagues further underscore the importance of focusing on improvements going forward.

“Guided by lessons learned, many of the remote assessments and trial efficiencies deployed during the pandemic can be preserved and improved upon. We strongly encourage use of these streamlined procedures where appropriate in future prospectively designed cancer clinical trials,” they wrote.

Dr. Flaherty reported receiving personal fees from numerous pharmaceutical companies. Dr. Ribas reported receiving grants from Agilent and Bristol Myers Squibb.

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

Many of the changes to cancer clinical trials forced through by the COVID-19 pandemic should remain, as they have made trials “more patient centered and efficient,” according to a group of thought leaders in oncology.

Among the potential improvements were more efficient study enrollment through secure electronic platforms, direct shipment of oral drugs to patients, remote assessment of adverse events, and streamlined data collection.

These changes should be implemented on a permanent basis, the group argues in a commentary published online July 21, 2021, in Cancer Discovery, a journal of the American Association for Cancer Research.

“The ability to distribute oral investigational drugs by mail to patients at their home has probably been the single most impactful change to clinical trial conduct, linked with virtual visits with patients to assess side effects and symptoms,” commented lead author Keith Flaherty, MD, who is director of clinical research at Massachusetts General Hospital, a professor at Harvard Medical School, Boston, and a member of the AACR board of directors.

“This has made it more feasible for patients for whom participation in clinical trials poses a disruption of their ability to work or provide care for family members to participate in trials,” he added in a press statement issued by the AACR.
 

Pandemic halted many clinical trials

A survey of cancer programs in early 2020 showed that nearly 60% halted screening and/or enrollment for at least some trials because of COVID-19.

“In the spring of 2020, clinical trial conduct halted and then restarted focusing on the bare minimum procedures that first allowed patients continued access to their experimental therapies, and then allowed clinical trial sites and sponsors to collect information on the effects of the therapies,” the authors said.

“The COVID-19–induced changes to clinical trials were a big challenge, probably the largest change in clinical trial conduct since the start of modern oncology clinical testing,” they commented.

“But it also represents an opportunity to rethink the key aspects of clinical trial conduct that are strictly necessary to reach the goal of testing the effectiveness of cancer therapies, and which others are dispensable or provide only minor additional contributions,” they added.

As previously reported at the time by this news organization, efforts to find alternative approaches to conducting trials amid the pandemic led to the emergence of a few “silver linings.”

Key adaptations made to clinical trials and highlighted by the authors include:

• Uptake of remote consenting and telemedicine
• Use of alternative laboratories and imaging centers
• Delivery or administration of investigational drugs at patients’ homes or local clinics
• Commercial attainment of study drugs already approved for other indications

Indeed, the restrictions encountered during the pandemic underscore the importance of designing patient-centered trials versus study site–centered trials, added Antoni Ribas, MD, commentary coauthor and immediate past president of the AACR.

Many of the changes implemented during the pandemic could help increase access for patients living in underserved communities who are underrepresented in clinical trials, he explained.
 

Harnessing the lessons learned

The authors also recommended the following additional adaptations, which they believe will enhance efficiency and further expand access to clinical trials:

• Incorporating patient-reported outcomes and alternative endpoints in efficacy assessments
• Aiming for 100% remote drug infusions and monitoring
• Increasing funding for clinical trials conducted in underserved communities
• Expanding clinical trial eligibility to include patients with a wide range of comorbidities
• Reducing collection of low-grade adverse events and allowing minor protocol deviations

The group’s recommendations are based on discussions by the AACR COVID-19 and Cancer Task Force, in which they participated.

The American Society of Clinical Oncology is also working to leverage pandemic-related lessons to streamline care and trial planning.

ASCO’s “Road to Recovery” recommendations, published in December 2020, aim to “ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality,” the authors explained.

Dr. Flaherty and colleagues further underscore the importance of focusing on improvements going forward.

“Guided by lessons learned, many of the remote assessments and trial efficiencies deployed during the pandemic can be preserved and improved upon. We strongly encourage use of these streamlined procedures where appropriate in future prospectively designed cancer clinical trials,” they wrote.

Dr. Flaherty reported receiving personal fees from numerous pharmaceutical companies. Dr. Ribas reported receiving grants from Agilent and Bristol Myers Squibb.

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

The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

The Food and Drug Administration has approved pembrolizumab (Keytruda) monotherapy for locally advanced cutaneous squamous cell carcinoma (cSCC) that can’t be cured by surgery or radiation.

The July 6 approval for the programmed death–1 inhibitor follows a June FDA approval for pembrolizumab monotherapy in patients with recurrent or metastatic cSCC disease not curable by surgery or radiation. Both approvals, pembrolizumab’s first for cSCC, are based on findings from the second interim analysis of the phase 2, multicenter, open-label KEYNOTE-629 trial.

The objective response rate in the cohort of 54 patients with locally advanced disease was 50%, including a complete response rate of 17% and a partial response rate of 33%. Duration of response was 6 months or longer in 81% of the 27 responders, and 12 months or longer in 37% of responders. After a median follow-up of 13.4 months, median duration of response had not yet been reached.

Pembrolizumab has previously received FDA approvals, either as monotherapy or in combination with other agents, for the treatment of numerous cancer types, including certain melanomas, non–small cell lung cancers, head and neck SCCs, classical Hodgkin lymphomas, primary mediastinal large B-cell lymphomas, urothelial carcinomas, microsatellite instability–high or mismatch repair–deficient cancers, and gastric, esophageal, cervical, hepatocellular, Merkel cell, renal cell, tumor mutational burden–high, and triple-negative breast cancers.

Patients in the KEYNOTE-629 trial received pembrolizumab at a dose of 200 mg IV every 3 weeks for 24 months or until documented disease progression or unacceptable toxicity.

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC in KEYNOTE-629 were similar to those observed in patients with melanoma or non–small cell lung cancer who were treated with pembrolizumab monotherapy in previous trials.

The checkpoint inhibitor can cause immune-mediated adverse reactions, which may be severe or fatal, according to Merck, the drug’s manufacturer. The reactions can occur in any organ system or tissue and can affect more than one body system simultaneously.

“Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation,” Merck explained in a press release, noting that “early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda.”

Depending on the severity of any reaction, treatment should be withheld or permanently discontinued, and corticosteroids administered if appropriate, Merck stated.

[email protected]

Breast and cervical cancer screenings declined sharply in the early months of the COVID-19 pandemic, particularly among certain racial and ethnic minority groups and rural populations, notes the U.S. Centers for Disease Control and Prevention.

The new data come from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), a program that provides cancer screening services to women with low income and inadequate health insurance.

The data show that the total number of screenings funded by the NBCCEDP declined by 87% for breast cancer screening and by 84% for cervical cancer screening in April 2020 in comparison with the previous 5-year averages for that month.

The declines in breast cancer screening varied from 84% among Hispanic women to 98% among American Indian/Alaskan Native women. The declines in cervical cancer screening varied from 82% among Black women to 92% among Asian Pacific Islander women.

In April 2020, breast cancer screening declined by 86% in metro areas, 88% in urban areas, and 89% in rural areas in comparison with respective 5-year averages. For cervical cancer screenings, the corresponding declines were 85%, 77%, and 82%.

The findings are consistent with those from studies conducted in insured populations, note the authors, led by the Amy DeGroff, PhD, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion.

“Prolonged delays in screening related to the COVID-19 pandemic may lead to delayed diagnoses, poor health consequences, and an increase in cancer disparities among women already experiencing health inequities,” the CDC states in a press release.

Women from racial and ethnic minority groups already face a disproportionate burden of cervical and breast cancers in the United States: Black women and Hispanic women have the highest rates of cervical cancer incidence (8.3 and 8.9 per 100,000 women, respectively, vs. 7.3 per 100,000 among White women) and the highest rates of cervical cancer deaths. Black women have the highest rate of breast cancer death (26.9 per 100,000 women, vs. 19.4 per 100,000 among White women), the study authors explain.

Although the volume of screening began to recover in May 2020 – test volumes for breast and cervical cancer were 39% and 40% below the 5-year average by June 2020 – breast cancer screening in rural areas remained 52% below the 5-year average, they report.

The findings were published online June 30 in Preventive Medicine.

“This study highlights a decline in cancer screening among women of racial and ethnic minority groups with low incomes when their access to medical services decreased at the beginning of the pandemic,” Dr. DeGroff comments in the CDC press release.

The findings “reinforce the need to safely maintain routine health care services during the pandemic, especially when the health care environment meets COVID-19 safety guidelines,” she adds.

The investigators used NBCCEDP administrative and program data reported to the CDC by awardees – organizations that receive funding to implement the NBCCEDP – to assess the impact of COVID-19 on the number of breast and cervical cancer screening tests administered through the program and the effects of COVID-19 on the availability of screening services and NBCCEDP awardees’ capacity to support partner clinics.

A total of 630,264 breast and 594,566 cervical cancer screening tests were conducted during the review period of January-June 2015-2020.

Despite COVID-related challenges, “a large number of awardees reported flexibility and creative efforts to reach women and support clinics’ resumption of clinical care, including screening, during the COVID-19 pandemic,” the authors write.

“[The] CDC encourages health care professionals to help minimize delays in testing by continuing routine cancer screening for women having symptoms or at high risk for breast or cervical cancer,” Dr. DeGroff commented. “The Early Detection Program can help women overcome barriers to health equity by educating them about the importance of routine screening, addressing their concerns about COVID-19 transmission, and helping them to safely access screening through interventions like patient navigation.”

Future studies will examine the effect of the pandemic on screening during the second half of 2020, when surges of COVID-19 and their timing varied geographically, they note.

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

Breast and cervical cancer screenings declined sharply in the early months of the COVID-19 pandemic, particularly among certain racial and ethnic minority groups and rural populations, notes the U.S. Centers for Disease Control and Prevention.

The new data come from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), a program that provides cancer screening services to women with low income and inadequate health insurance.

The data show that the total number of screenings funded by the NBCCEDP declined by 87% for breast cancer screening and by 84% for cervical cancer screening in April 2020 in comparison with the previous 5-year averages for that month.

The declines in breast cancer screening varied from 84% among Hispanic women to 98% among American Indian/Alaskan Native women. The declines in cervical cancer screening varied from 82% among Black women to 92% among Asian Pacific Islander women.

In April 2020, breast cancer screening declined by 86% in metro areas, 88% in urban areas, and 89% in rural areas in comparison with respective 5-year averages. For cervical cancer screenings, the corresponding declines were 85%, 77%, and 82%.

The findings are consistent with those from studies conducted in insured populations, note the authors, led by the Amy DeGroff, PhD, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion.

“Prolonged delays in screening related to the COVID-19 pandemic may lead to delayed diagnoses, poor health consequences, and an increase in cancer disparities among women already experiencing health inequities,” the CDC states in a press release.

Women from racial and ethnic minority groups already face a disproportionate burden of cervical and breast cancers in the United States: Black women and Hispanic women have the highest rates of cervical cancer incidence (8.3 and 8.9 per 100,000 women, respectively, vs. 7.3 per 100,000 among White women) and the highest rates of cervical cancer deaths. Black women have the highest rate of breast cancer death (26.9 per 100,000 women, vs. 19.4 per 100,000 among White women), the study authors explain.

Although the volume of screening began to recover in May 2020 – test volumes for breast and cervical cancer were 39% and 40% below the 5-year average by June 2020 – breast cancer screening in rural areas remained 52% below the 5-year average, they report.

The findings were published online June 30 in Preventive Medicine.

“This study highlights a decline in cancer screening among women of racial and ethnic minority groups with low incomes when their access to medical services decreased at the beginning of the pandemic,” Dr. DeGroff comments in the CDC press release.

The findings “reinforce the need to safely maintain routine health care services during the pandemic, especially when the health care environment meets COVID-19 safety guidelines,” she adds.

The investigators used NBCCEDP administrative and program data reported to the CDC by awardees – organizations that receive funding to implement the NBCCEDP – to assess the impact of COVID-19 on the number of breast and cervical cancer screening tests administered through the program and the effects of COVID-19 on the availability of screening services and NBCCEDP awardees’ capacity to support partner clinics.

A total of 630,264 breast and 594,566 cervical cancer screening tests were conducted during the review period of January-June 2015-2020.

Despite COVID-related challenges, “a large number of awardees reported flexibility and creative efforts to reach women and support clinics’ resumption of clinical care, including screening, during the COVID-19 pandemic,” the authors write.

“[The] CDC encourages health care professionals to help minimize delays in testing by continuing routine cancer screening for women having symptoms or at high risk for breast or cervical cancer,” Dr. DeGroff commented. “The Early Detection Program can help women overcome barriers to health equity by educating them about the importance of routine screening, addressing their concerns about COVID-19 transmission, and helping them to safely access screening through interventions like patient navigation.”

Future studies will examine the effect of the pandemic on screening during the second half of 2020, when surges of COVID-19 and their timing varied geographically, they note.

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

Breast and cervical cancer screenings declined sharply in the early months of the COVID-19 pandemic, particularly among certain racial and ethnic minority groups and rural populations, notes the U.S. Centers for Disease Control and Prevention.

The new data come from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), a program that provides cancer screening services to women with low income and inadequate health insurance.

The data show that the total number of screenings funded by the NBCCEDP declined by 87% for breast cancer screening and by 84% for cervical cancer screening in April 2020 in comparison with the previous 5-year averages for that month.

The declines in breast cancer screening varied from 84% among Hispanic women to 98% among American Indian/Alaskan Native women. The declines in cervical cancer screening varied from 82% among Black women to 92% among Asian Pacific Islander women.

In April 2020, breast cancer screening declined by 86% in metro areas, 88% in urban areas, and 89% in rural areas in comparison with respective 5-year averages. For cervical cancer screenings, the corresponding declines were 85%, 77%, and 82%.

The findings are consistent with those from studies conducted in insured populations, note the authors, led by the Amy DeGroff, PhD, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion.

“Prolonged delays in screening related to the COVID-19 pandemic may lead to delayed diagnoses, poor health consequences, and an increase in cancer disparities among women already experiencing health inequities,” the CDC states in a press release.

Women from racial and ethnic minority groups already face a disproportionate burden of cervical and breast cancers in the United States: Black women and Hispanic women have the highest rates of cervical cancer incidence (8.3 and 8.9 per 100,000 women, respectively, vs. 7.3 per 100,000 among White women) and the highest rates of cervical cancer deaths. Black women have the highest rate of breast cancer death (26.9 per 100,000 women, vs. 19.4 per 100,000 among White women), the study authors explain.

Although the volume of screening began to recover in May 2020 – test volumes for breast and cervical cancer were 39% and 40% below the 5-year average by June 2020 – breast cancer screening in rural areas remained 52% below the 5-year average, they report.

The findings were published online June 30 in Preventive Medicine.

“This study highlights a decline in cancer screening among women of racial and ethnic minority groups with low incomes when their access to medical services decreased at the beginning of the pandemic,” Dr. DeGroff comments in the CDC press release.

The findings “reinforce the need to safely maintain routine health care services during the pandemic, especially when the health care environment meets COVID-19 safety guidelines,” she adds.

The investigators used NBCCEDP administrative and program data reported to the CDC by awardees – organizations that receive funding to implement the NBCCEDP – to assess the impact of COVID-19 on the number of breast and cervical cancer screening tests administered through the program and the effects of COVID-19 on the availability of screening services and NBCCEDP awardees’ capacity to support partner clinics.

A total of 630,264 breast and 594,566 cervical cancer screening tests were conducted during the review period of January-June 2015-2020.

Despite COVID-related challenges, “a large number of awardees reported flexibility and creative efforts to reach women and support clinics’ resumption of clinical care, including screening, during the COVID-19 pandemic,” the authors write.

“[The] CDC encourages health care professionals to help minimize delays in testing by continuing routine cancer screening for women having symptoms or at high risk for breast or cervical cancer,” Dr. DeGroff commented. “The Early Detection Program can help women overcome barriers to health equity by educating them about the importance of routine screening, addressing their concerns about COVID-19 transmission, and helping them to safely access screening through interventions like patient navigation.”

Future studies will examine the effect of the pandemic on screening during the second half of 2020, when surges of COVID-19 and their timing varied geographically, they note.

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

The European Commission (EC) has approved cemiplimab (Libtayo) for the treatment of adults with locally advanced or metastatic basal cell carcinoma (BCC) who progressed on – or could not tolerate – treatment with a hedgehog pathway inhibitor (HHI).

The programmed death-1 (PD-1) inhibitor, which is being jointly developed by Regeneron and Sanofi under a global collaboration agreement, was approved by the Food and Drug Administration for this indication in the United States in February; the FDA granted full approval for its use in patients with locally advanced BCC and accelerated approval for use in patients with metastatic BCC.

The EC’s thumbs-up for cemiplimab as a treatment for BCC marks the third such approval for an advanced cancer in the European Union: The immunotherapy was concurrently approved by the EC for the first-line treatment of adults with advanced non–small cell lung cancer (NSCLC) whose tumor cells have ≥ 50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations, and was approved in 2019 for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.

The FDA granted approval of cemiplimab for NSCLC in February, and for CSCC in 2018.

The latest BCC approval is based on data from an ongoing, open-label, prospective phase 2 clinical trial of 119 patients with advanced BCC who were previously treated with an HHI. The objective response rates in cemiplimab-treated patients were 32% (partial responses in 25%; complete responses in 7%) in those with locally advanced BCC, and 29% (partial responses in 26%; complete responses in 3%) in those with metastatic BCC.

About 90% of all patients had a duration of response (DOR) of 6 months or longer. Median DOR was not reached in either group at median follow-up of 16 months for locally advanced BCC and 9 months for metastatic BCC.

The safety profile of cemiplimab has been generally consistent across approved indications. Serious adverse events have been reported in 30% of 816 patients from all four cemiplimab monotherapy pivotal trials, and these led to permanent discontinuation of treatment in 8% of patients.

Immune-related adverse reactions occurred in 22% of patients, and led to permanent discontinuation in 4%. The most common such reactions were hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin adverse reactions (2%).

Cemiplimab is administered by intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. The recommended dose is 350 mg.

A press release from Regeneron notes that research efforts with respect to cemiplimab – both as monotherapy and in combination with other agents – are focused on difficult-to-treat cancers, including advanced NSCLC, cervical cancer, and other solid tumors and blood cancers.

The European Commission (EC) has approved cemiplimab (Libtayo) for the treatment of adults with locally advanced or metastatic basal cell carcinoma (BCC) who progressed on – or could not tolerate – treatment with a hedgehog pathway inhibitor (HHI).

The programmed death-1 (PD-1) inhibitor, which is being jointly developed by Regeneron and Sanofi under a global collaboration agreement, was approved by the Food and Drug Administration for this indication in the United States in February; the FDA granted full approval for its use in patients with locally advanced BCC and accelerated approval for use in patients with metastatic BCC.

The EC’s thumbs-up for cemiplimab as a treatment for BCC marks the third such approval for an advanced cancer in the European Union: The immunotherapy was concurrently approved by the EC for the first-line treatment of adults with advanced non–small cell lung cancer (NSCLC) whose tumor cells have ≥ 50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations, and was approved in 2019 for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.

The FDA granted approval of cemiplimab for NSCLC in February, and for CSCC in 2018.

The latest BCC approval is based on data from an ongoing, open-label, prospective phase 2 clinical trial of 119 patients with advanced BCC who were previously treated with an HHI. The objective response rates in cemiplimab-treated patients were 32% (partial responses in 25%; complete responses in 7%) in those with locally advanced BCC, and 29% (partial responses in 26%; complete responses in 3%) in those with metastatic BCC.

About 90% of all patients had a duration of response (DOR) of 6 months or longer. Median DOR was not reached in either group at median follow-up of 16 months for locally advanced BCC and 9 months for metastatic BCC.

The safety profile of cemiplimab has been generally consistent across approved indications. Serious adverse events have been reported in 30% of 816 patients from all four cemiplimab monotherapy pivotal trials, and these led to permanent discontinuation of treatment in 8% of patients.

Immune-related adverse reactions occurred in 22% of patients, and led to permanent discontinuation in 4%. The most common such reactions were hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin adverse reactions (2%).

Cemiplimab is administered by intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. The recommended dose is 350 mg.

A press release from Regeneron notes that research efforts with respect to cemiplimab – both as monotherapy and in combination with other agents – are focused on difficult-to-treat cancers, including advanced NSCLC, cervical cancer, and other solid tumors and blood cancers.

The European Commission (EC) has approved cemiplimab (Libtayo) for the treatment of adults with locally advanced or metastatic basal cell carcinoma (BCC) who progressed on – or could not tolerate – treatment with a hedgehog pathway inhibitor (HHI).

The programmed death-1 (PD-1) inhibitor, which is being jointly developed by Regeneron and Sanofi under a global collaboration agreement, was approved by the Food and Drug Administration for this indication in the United States in February; the FDA granted full approval for its use in patients with locally advanced BCC and accelerated approval for use in patients with metastatic BCC.

The EC’s thumbs-up for cemiplimab as a treatment for BCC marks the third such approval for an advanced cancer in the European Union: The immunotherapy was concurrently approved by the EC for the first-line treatment of adults with advanced non–small cell lung cancer (NSCLC) whose tumor cells have ≥ 50% PD-L1 expression and no EGFR, ALK or ROS1 aberrations, and was approved in 2019 for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.

The FDA granted approval of cemiplimab for NSCLC in February, and for CSCC in 2018.

The latest BCC approval is based on data from an ongoing, open-label, prospective phase 2 clinical trial of 119 patients with advanced BCC who were previously treated with an HHI. The objective response rates in cemiplimab-treated patients were 32% (partial responses in 25%; complete responses in 7%) in those with locally advanced BCC, and 29% (partial responses in 26%; complete responses in 3%) in those with metastatic BCC.

About 90% of all patients had a duration of response (DOR) of 6 months or longer. Median DOR was not reached in either group at median follow-up of 16 months for locally advanced BCC and 9 months for metastatic BCC.

The safety profile of cemiplimab has been generally consistent across approved indications. Serious adverse events have been reported in 30% of 816 patients from all four cemiplimab monotherapy pivotal trials, and these led to permanent discontinuation of treatment in 8% of patients.

Immune-related adverse reactions occurred in 22% of patients, and led to permanent discontinuation in 4%. The most common such reactions were hypothyroidism (8%), hyperthyroidism (3%), pneumonitis (3%), hepatitis (2%), colitis (2%) and immune-related skin adverse reactions (2%).

Cemiplimab is administered by intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. The recommended dose is 350 mg.

A press release from Regeneron notes that research efforts with respect to cemiplimab – both as monotherapy and in combination with other agents – are focused on difficult-to-treat cancers, including advanced NSCLC, cervical cancer, and other solid tumors and blood cancers.

The American Society of Clinical Oncology (ASCO) now recommends offering 1 year of adjuvant olaparib therapy to patients with early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The change in management of hereditary breast cancer is outlined in an update to 2020 guidelines, and it comes as a “rapid recommendation” on the heels of the phase 3 OlympiA trial results, which indicated a 42% improvement in invasive and distant disease-free survival with the PARP inhibitor olaparib (Lynparza) in comparison with placebo.

The OlympiA trial results, as reported by this news organization, were presented during the plenary session of the ASCO 2021 annual meeting and were published June 3 in The New England Journal of Medicine.

“These clear and positive data prompted ASCO to issue a provisional update of the guideline recommendation focused specifically on the role of olaparib in this setting,” states an ASCO press release.

The previous 2020 guidelines stated: “There are insufficient data ... to recommend a PARP inhibitor for patients with nonmetastatic breast cancer.” The OlympiA trial changed that. ASCO now recommends that patients with early-stage, HER2-negative, BRCA-mutated breast cancer at high risk for recurrence be offered olaparib after completion of chemotherapy and local treatment, including radiotherapy.

The update states: “For those who had surgery first, adjuvant olaparib is recommended for patients with TNBC [triple-negative breast cancer] and tumor size greater than 2 cm or any involved axillary nodes. For patients with hormone receptor–positive disease, adjuvant olaparib is recommended for those with at least four involved axillary lymph nodes. For patients who had neoadjuvant chemotherapy, adjuvant olaparib is recommended for patients with TNBC and any residual cancer. Adjuvant olaparib is recommended for patients with residual disease and an estrogen receptor status and tumor grade (CSP+EG) score greater than or equal to 3.”

“The findings from the OlympiA trial – presented just last week – mark a significant improvement in the care of these patients,” Julie Garlow, MD, ASCO’s executive vice president and chief medical officer, states in the ASCO press release.

“ASCO’s Expert Guideline Panel and Evidence-based Medicine Committee noted this and then quickly produced and provisionally approved this guideline update to enable patients to begin to benefit from this research advance as quickly as possible,” she said.

A formal assessment and submission for publication in the Journal of Clinical Oncology will follow the release notes.

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

The American Society of Clinical Oncology (ASCO) now recommends offering 1 year of adjuvant olaparib therapy to patients with early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The change in management of hereditary breast cancer is outlined in an update to 2020 guidelines, and it comes as a “rapid recommendation” on the heels of the phase 3 OlympiA trial results, which indicated a 42% improvement in invasive and distant disease-free survival with the PARP inhibitor olaparib (Lynparza) in comparison with placebo.

The OlympiA trial results, as reported by this news organization, were presented during the plenary session of the ASCO 2021 annual meeting and were published June 3 in The New England Journal of Medicine.

“These clear and positive data prompted ASCO to issue a provisional update of the guideline recommendation focused specifically on the role of olaparib in this setting,” states an ASCO press release.

The previous 2020 guidelines stated: “There are insufficient data ... to recommend a PARP inhibitor for patients with nonmetastatic breast cancer.” The OlympiA trial changed that. ASCO now recommends that patients with early-stage, HER2-negative, BRCA-mutated breast cancer at high risk for recurrence be offered olaparib after completion of chemotherapy and local treatment, including radiotherapy.

The update states: “For those who had surgery first, adjuvant olaparib is recommended for patients with TNBC [triple-negative breast cancer] and tumor size greater than 2 cm or any involved axillary nodes. For patients with hormone receptor–positive disease, adjuvant olaparib is recommended for those with at least four involved axillary lymph nodes. For patients who had neoadjuvant chemotherapy, adjuvant olaparib is recommended for patients with TNBC and any residual cancer. Adjuvant olaparib is recommended for patients with residual disease and an estrogen receptor status and tumor grade (CSP+EG) score greater than or equal to 3.”

“The findings from the OlympiA trial – presented just last week – mark a significant improvement in the care of these patients,” Julie Garlow, MD, ASCO’s executive vice president and chief medical officer, states in the ASCO press release.

“ASCO’s Expert Guideline Panel and Evidence-based Medicine Committee noted this and then quickly produced and provisionally approved this guideline update to enable patients to begin to benefit from this research advance as quickly as possible,” she said.

A formal assessment and submission for publication in the Journal of Clinical Oncology will follow the release notes.

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

The American Society of Clinical Oncology (ASCO) now recommends offering 1 year of adjuvant olaparib therapy to patients with early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.

The change in management of hereditary breast cancer is outlined in an update to 2020 guidelines, and it comes as a “rapid recommendation” on the heels of the phase 3 OlympiA trial results, which indicated a 42% improvement in invasive and distant disease-free survival with the PARP inhibitor olaparib (Lynparza) in comparison with placebo.

The OlympiA trial results, as reported by this news organization, were presented during the plenary session of the ASCO 2021 annual meeting and were published June 3 in The New England Journal of Medicine.

“These clear and positive data prompted ASCO to issue a provisional update of the guideline recommendation focused specifically on the role of olaparib in this setting,” states an ASCO press release.

The previous 2020 guidelines stated: “There are insufficient data ... to recommend a PARP inhibitor for patients with nonmetastatic breast cancer.” The OlympiA trial changed that. ASCO now recommends that patients with early-stage, HER2-negative, BRCA-mutated breast cancer at high risk for recurrence be offered olaparib after completion of chemotherapy and local treatment, including radiotherapy.

The update states: “For those who had surgery first, adjuvant olaparib is recommended for patients with TNBC [triple-negative breast cancer] and tumor size greater than 2 cm or any involved axillary nodes. For patients with hormone receptor–positive disease, adjuvant olaparib is recommended for those with at least four involved axillary lymph nodes. For patients who had neoadjuvant chemotherapy, adjuvant olaparib is recommended for patients with TNBC and any residual cancer. Adjuvant olaparib is recommended for patients with residual disease and an estrogen receptor status and tumor grade (CSP+EG) score greater than or equal to 3.”

“The findings from the OlympiA trial – presented just last week – mark a significant improvement in the care of these patients,” Julie Garlow, MD, ASCO’s executive vice president and chief medical officer, states in the ASCO press release.

“ASCO’s Expert Guideline Panel and Evidence-based Medicine Committee noted this and then quickly produced and provisionally approved this guideline update to enable patients to begin to benefit from this research advance as quickly as possible,” she said.

A formal assessment and submission for publication in the Journal of Clinical Oncology will follow the release notes.

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

A biosignature tool helps women avoid unnecessary radiotherapy after undergoing lumpectomy for ductal carcinoma in situ (DCIS) – and also identifies women who need more intense treatment.

The DCISionRT test (PreludeDx) and its response subtype (Rst) biosignature provide personalized risk assessment, explains Frank Vicini, MD, a radiation oncologist at GenesisCare and a member of NRG Oncology, Pontiac, Mich.

He presented data on the test at a poster at the recent American Society of Clinical Oncology Annual Meeting.

This test and biosignature can identify women who are at low risk for recurrence risk and who could potentially forgo radiotherapy after surgery. They can also identify patients who would likely benefit from radiotherapy, Dr. Vicini reported.

The tool shows promise for identifying those whose cancer is likely to recur despite undergoing postlumpectomy radiotherapy – women who might benefit from intensified or alternate treatment approaches, he added.

The latter finding is particularly provocative because it suggests that the biosignatures “may appropriately identify patients with very radioresistant ductal carcinoma in situ,” Benjamin D. Smith, MD, commented during a poster discussion session at the meeting.

“I think these findings merit validation in translational research models,” said Dr. Smith, a radiation oncologist and professor of radiation oncology and health services research at the University of Texas MD Anderson Cancer Center, Houston.
 

DCISionRT, Rst, and risk

DCISionRT combines molecular biology innovations with risk-based scores to assess risk for recurrence, which is classified as either low or elevated, according to the test developer, PreludeDx.

Dr. Vicini and colleagues used the test to classify tissue samples from 485 women who were part of previous DCISionRT validation cohorts in Sweden, Australia, and the United States. The patients underwent breast cancer surgery (BCS) with or without radiotherapy between 1996 and 2011.

The Rst biosignature was used to further categorize those in the elevated-risk group as having a good response subtype (good Rst) or a poor response subtype (poor Rst) after BCS plus radiotherapy.

Radiotherapy was associated with significantly reduced recurrence rates among women with elevated risk and a good Rst (the hazard ratios for ipsilateral breast tumor recurrence [IBTR] and invasive breast cancer [IBC] were 0.18 and 0.15, respectively).

No radiotherapy benefit was seen among those with elevated risk and poor Rst.

The investigators also reported that, among patients with a poor Rst, 10-year IBTR and IBC rates were 25% and 16%, respectively, regardless of whether they received radiotherapy. These rates were much higher than the rates among women with good Rst (6.6% and 4.5%; hazard ratio, 3.6 and 4.4, respectively).

No significant difference was seen in 10-year IBTR and IBC rates among patients in the low-risk group, with or without radiotherapy.

Traditional clinicopathologic risk factors, including age younger than 50 years, grade 3 disease, and tumor size greater than 2.5 cm, did not identify poor versus good response subtypes in this cohort, and on multivariable analysis, neither of these factors nor endocrine therapy was significantly associated with IBTR or IBC.
 

Prospective validation needed

In his discussion, Dr. Smith said that the study provides “important data” that further validate the DCISionRT platform alone for assessing risk among women with DCIS who undergo BCS. But it is the Rst biosignature, which allows clinicians to “predict radioresistance of residual malignant chromogens following lumpectomy plus radiation therapy,” that really stands out, he added.

From the data presented, “it is reasonable to conclude that patients with a poor Rst score treated with lumpectomy and radiation had a much higher risk of in-breast tumor recurrence than one might predict or anticipate based on existing published randomized clinical trial data,” he said.

“In my opinion, it is very important to prospectively validate this finding with other cohorts,” he said. “Moving forward, I think there may come a time where there may be interest in studying radiosensitizing agents for poor-Rst ductal carcinoma in situ that are resistant to standard doses of radiation, and it may be that we consider the Rst as a factor moving forward in selecting patients for BCT versus mastectomy.”

However, because 75% of patients at elevated risk with poor Rst who undergo lumpectomy and radiotherapy do not experience recurrence in the decade following their treatment, it would be “inappropriate and misguided” to start recommending mastectomy for patients at DCISionRT elevated risk who have poor Rst, he said.

The study was funded by PreludeDx. Dr. Vicini reported employment with 21st Century Oncology and financial relationships with ImpediMed, Prelude Therapeutics, and Concure Oncology. Dr. Smith, through his employer, has an equity interest in Oncora Medical through a partnership agreement. He also has an uncompensated relationship with the American Society for Radiation Oncology.

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

A biosignature tool helps women avoid unnecessary radiotherapy after undergoing lumpectomy for ductal carcinoma in situ (DCIS) – and also identifies women who need more intense treatment.

The DCISionRT test (PreludeDx) and its response subtype (Rst) biosignature provide personalized risk assessment, explains Frank Vicini, MD, a radiation oncologist at GenesisCare and a member of NRG Oncology, Pontiac, Mich.

He presented data on the test at a poster at the recent American Society of Clinical Oncology Annual Meeting.

This test and biosignature can identify women who are at low risk for recurrence risk and who could potentially forgo radiotherapy after surgery. They can also identify patients who would likely benefit from radiotherapy, Dr. Vicini reported.

The tool shows promise for identifying those whose cancer is likely to recur despite undergoing postlumpectomy radiotherapy – women who might benefit from intensified or alternate treatment approaches, he added.

The latter finding is particularly provocative because it suggests that the biosignatures “may appropriately identify patients with very radioresistant ductal carcinoma in situ,” Benjamin D. Smith, MD, commented during a poster discussion session at the meeting.

“I think these findings merit validation in translational research models,” said Dr. Smith, a radiation oncologist and professor of radiation oncology and health services research at the University of Texas MD Anderson Cancer Center, Houston.
 

DCISionRT, Rst, and risk

DCISionRT combines molecular biology innovations with risk-based scores to assess risk for recurrence, which is classified as either low or elevated, according to the test developer, PreludeDx.

Dr. Vicini and colleagues used the test to classify tissue samples from 485 women who were part of previous DCISionRT validation cohorts in Sweden, Australia, and the United States. The patients underwent breast cancer surgery (BCS) with or without radiotherapy between 1996 and 2011.

The Rst biosignature was used to further categorize those in the elevated-risk group as having a good response subtype (good Rst) or a poor response subtype (poor Rst) after BCS plus radiotherapy.

Radiotherapy was associated with significantly reduced recurrence rates among women with elevated risk and a good Rst (the hazard ratios for ipsilateral breast tumor recurrence [IBTR] and invasive breast cancer [IBC] were 0.18 and 0.15, respectively).

No radiotherapy benefit was seen among those with elevated risk and poor Rst.

The investigators also reported that, among patients with a poor Rst, 10-year IBTR and IBC rates were 25% and 16%, respectively, regardless of whether they received radiotherapy. These rates were much higher than the rates among women with good Rst (6.6% and 4.5%; hazard ratio, 3.6 and 4.4, respectively).

No significant difference was seen in 10-year IBTR and IBC rates among patients in the low-risk group, with or without radiotherapy.

Traditional clinicopathologic risk factors, including age younger than 50 years, grade 3 disease, and tumor size greater than 2.5 cm, did not identify poor versus good response subtypes in this cohort, and on multivariable analysis, neither of these factors nor endocrine therapy was significantly associated with IBTR or IBC.
 

Prospective validation needed

In his discussion, Dr. Smith said that the study provides “important data” that further validate the DCISionRT platform alone for assessing risk among women with DCIS who undergo BCS. But it is the Rst biosignature, which allows clinicians to “predict radioresistance of residual malignant chromogens following lumpectomy plus radiation therapy,” that really stands out, he added.

From the data presented, “it is reasonable to conclude that patients with a poor Rst score treated with lumpectomy and radiation had a much higher risk of in-breast tumor recurrence than one might predict or anticipate based on existing published randomized clinical trial data,” he said.

“In my opinion, it is very important to prospectively validate this finding with other cohorts,” he said. “Moving forward, I think there may come a time where there may be interest in studying radiosensitizing agents for poor-Rst ductal carcinoma in situ that are resistant to standard doses of radiation, and it may be that we consider the Rst as a factor moving forward in selecting patients for BCT versus mastectomy.”

However, because 75% of patients at elevated risk with poor Rst who undergo lumpectomy and radiotherapy do not experience recurrence in the decade following their treatment, it would be “inappropriate and misguided” to start recommending mastectomy for patients at DCISionRT elevated risk who have poor Rst, he said.

The study was funded by PreludeDx. Dr. Vicini reported employment with 21st Century Oncology and financial relationships with ImpediMed, Prelude Therapeutics, and Concure Oncology. Dr. Smith, through his employer, has an equity interest in Oncora Medical through a partnership agreement. He also has an uncompensated relationship with the American Society for Radiation Oncology.

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

A biosignature tool helps women avoid unnecessary radiotherapy after undergoing lumpectomy for ductal carcinoma in situ (DCIS) – and also identifies women who need more intense treatment.

The DCISionRT test (PreludeDx) and its response subtype (Rst) biosignature provide personalized risk assessment, explains Frank Vicini, MD, a radiation oncologist at GenesisCare and a member of NRG Oncology, Pontiac, Mich.

He presented data on the test at a poster at the recent American Society of Clinical Oncology Annual Meeting.

This test and biosignature can identify women who are at low risk for recurrence risk and who could potentially forgo radiotherapy after surgery. They can also identify patients who would likely benefit from radiotherapy, Dr. Vicini reported.

The tool shows promise for identifying those whose cancer is likely to recur despite undergoing postlumpectomy radiotherapy – women who might benefit from intensified or alternate treatment approaches, he added.

The latter finding is particularly provocative because it suggests that the biosignatures “may appropriately identify patients with very radioresistant ductal carcinoma in situ,” Benjamin D. Smith, MD, commented during a poster discussion session at the meeting.

“I think these findings merit validation in translational research models,” said Dr. Smith, a radiation oncologist and professor of radiation oncology and health services research at the University of Texas MD Anderson Cancer Center, Houston.
 

DCISionRT, Rst, and risk

DCISionRT combines molecular biology innovations with risk-based scores to assess risk for recurrence, which is classified as either low or elevated, according to the test developer, PreludeDx.

Dr. Vicini and colleagues used the test to classify tissue samples from 485 women who were part of previous DCISionRT validation cohorts in Sweden, Australia, and the United States. The patients underwent breast cancer surgery (BCS) with or without radiotherapy between 1996 and 2011.

The Rst biosignature was used to further categorize those in the elevated-risk group as having a good response subtype (good Rst) or a poor response subtype (poor Rst) after BCS plus radiotherapy.

Radiotherapy was associated with significantly reduced recurrence rates among women with elevated risk and a good Rst (the hazard ratios for ipsilateral breast tumor recurrence [IBTR] and invasive breast cancer [IBC] were 0.18 and 0.15, respectively).

No radiotherapy benefit was seen among those with elevated risk and poor Rst.

The investigators also reported that, among patients with a poor Rst, 10-year IBTR and IBC rates were 25% and 16%, respectively, regardless of whether they received radiotherapy. These rates were much higher than the rates among women with good Rst (6.6% and 4.5%; hazard ratio, 3.6 and 4.4, respectively).

No significant difference was seen in 10-year IBTR and IBC rates among patients in the low-risk group, with or without radiotherapy.

Traditional clinicopathologic risk factors, including age younger than 50 years, grade 3 disease, and tumor size greater than 2.5 cm, did not identify poor versus good response subtypes in this cohort, and on multivariable analysis, neither of these factors nor endocrine therapy was significantly associated with IBTR or IBC.
 

Prospective validation needed

In his discussion, Dr. Smith said that the study provides “important data” that further validate the DCISionRT platform alone for assessing risk among women with DCIS who undergo BCS. But it is the Rst biosignature, which allows clinicians to “predict radioresistance of residual malignant chromogens following lumpectomy plus radiation therapy,” that really stands out, he added.

From the data presented, “it is reasonable to conclude that patients with a poor Rst score treated with lumpectomy and radiation had a much higher risk of in-breast tumor recurrence than one might predict or anticipate based on existing published randomized clinical trial data,” he said.

“In my opinion, it is very important to prospectively validate this finding with other cohorts,” he said. “Moving forward, I think there may come a time where there may be interest in studying radiosensitizing agents for poor-Rst ductal carcinoma in situ that are resistant to standard doses of radiation, and it may be that we consider the Rst as a factor moving forward in selecting patients for BCT versus mastectomy.”

However, because 75% of patients at elevated risk with poor Rst who undergo lumpectomy and radiotherapy do not experience recurrence in the decade following their treatment, it would be “inappropriate and misguided” to start recommending mastectomy for patients at DCISionRT elevated risk who have poor Rst, he said.

The study was funded by PreludeDx. Dr. Vicini reported employment with 21st Century Oncology and financial relationships with ImpediMed, Prelude Therapeutics, and Concure Oncology. Dr. Smith, through his employer, has an equity interest in Oncora Medical through a partnership agreement. He also has an uncompensated relationship with the American Society for Radiation Oncology.

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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