Breast Cancer

Key clinical point: The detrimental effects of chemotherapy on quality of life (QoL) are significant at 12 months in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either chemotherapy plus trastuzumab vs. trastuzumab monotherapy. There was no difference in QoL after 36 months between treatments.

Major finding: At 12 months, the proportion of patients showing QoL deterioration was significantly lower in the trastuzumab monotherapy vs. trastuzumab plus chemotherapy group (19% vs. 38%; P = .009). A significantly higher number of patients showed improvement in QoL with trastuzumab monotherapy at 12 months (43% vs. 25%; P = .021). No difference was reported in any QoL items at 36 months between the 2 treatment groups.

Study details: The QoL analysis of phase 3, randomized RESPECT trial included 231 older patients with HER2-positive breast cancer who received either trastuzumab monotherapy (mean age, 73.9 years) or trastuzumab plus chemotherapy (mean age, 73.7 years).

Disclosures: The analysis was supported by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan. The authors received consulting fees, honoraria, and research funding outside this work.

Source: Taira N et al. J Clin Oncol. 2021 Apr 9. doi: 10.1200/JCO.20.02751.

Key clinical point: The detrimental effects of chemotherapy on quality of life (QoL) are significant at 12 months in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either chemotherapy plus trastuzumab vs. trastuzumab monotherapy. There was no difference in QoL after 36 months between treatments.

Major finding: At 12 months, the proportion of patients showing QoL deterioration was significantly lower in the trastuzumab monotherapy vs. trastuzumab plus chemotherapy group (19% vs. 38%; P = .009). A significantly higher number of patients showed improvement in QoL with trastuzumab monotherapy at 12 months (43% vs. 25%; P = .021). No difference was reported in any QoL items at 36 months between the 2 treatment groups.

Study details: The QoL analysis of phase 3, randomized RESPECT trial included 231 older patients with HER2-positive breast cancer who received either trastuzumab monotherapy (mean age, 73.9 years) or trastuzumab plus chemotherapy (mean age, 73.7 years).

Disclosures: The analysis was supported by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan. The authors received consulting fees, honoraria, and research funding outside this work.

Source: Taira N et al. J Clin Oncol. 2021 Apr 9. doi: 10.1200/JCO.20.02751.

Key clinical point: The detrimental effects of chemotherapy on quality of life (QoL) are significant at 12 months in older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either chemotherapy plus trastuzumab vs. trastuzumab monotherapy. There was no difference in QoL after 36 months between treatments.

Major finding: At 12 months, the proportion of patients showing QoL deterioration was significantly lower in the trastuzumab monotherapy vs. trastuzumab plus chemotherapy group (19% vs. 38%; P = .009). A significantly higher number of patients showed improvement in QoL with trastuzumab monotherapy at 12 months (43% vs. 25%; P = .021). No difference was reported in any QoL items at 36 months between the 2 treatment groups.

Study details: The QoL analysis of phase 3, randomized RESPECT trial included 231 older patients with HER2-positive breast cancer who received either trastuzumab monotherapy (mean age, 73.9 years) or trastuzumab plus chemotherapy (mean age, 73.7 years).

Disclosures: The analysis was supported by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation, Japan. The authors received consulting fees, honoraria, and research funding outside this work.

Source: Taira N et al. J Clin Oncol. 2021 Apr 9. doi: 10.1200/JCO.20.02751.

Key clinical point: Pembrolizumab plus eribulin shows activity in patients with heavily pretreated, hormone-receptor–positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent, or metastatic breast cancer.

Major finding: The clinical benefit rate was 56.8%, and the objective response rate was 40.9%. The median progression-free survival was 6.0 months. The serious adverse event rate was 31.8%, and 25.0% of patients experienced immune-related adverse events.

Study details: Phase 2 study of 44 previously treated patients with HR+, HER-negative, inoperable, locally recurrent breast cancer received pembrolizumab plus eribulin.

Disclosures: The study was supported by MSD Spain. Some of the authors declared receiving consulting fees, honoraria, travel expenses and/or research funding from various sources.

Source: Pérez-García JM et al. Eur J Cancer. 2021 Mar 29. doi: 10.1016/j.ejca.2021.02.028.

Key clinical point: Pembrolizumab plus eribulin shows activity in patients with heavily pretreated, hormone-receptor–positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent, or metastatic breast cancer.

Major finding: The clinical benefit rate was 56.8%, and the objective response rate was 40.9%. The median progression-free survival was 6.0 months. The serious adverse event rate was 31.8%, and 25.0% of patients experienced immune-related adverse events.

Study details: Phase 2 study of 44 previously treated patients with HR+, HER-negative, inoperable, locally recurrent breast cancer received pembrolizumab plus eribulin.

Disclosures: The study was supported by MSD Spain. Some of the authors declared receiving consulting fees, honoraria, travel expenses and/or research funding from various sources.

Source: Pérez-García JM et al. Eur J Cancer. 2021 Mar 29. doi: 10.1016/j.ejca.2021.02.028.

Key clinical point: Pembrolizumab plus eribulin shows activity in patients with heavily pretreated, hormone-receptor–positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative, locally recurrent, or metastatic breast cancer.

Major finding: The clinical benefit rate was 56.8%, and the objective response rate was 40.9%. The median progression-free survival was 6.0 months. The serious adverse event rate was 31.8%, and 25.0% of patients experienced immune-related adverse events.

Study details: Phase 2 study of 44 previously treated patients with HR+, HER-negative, inoperable, locally recurrent breast cancer received pembrolizumab plus eribulin.

Disclosures: The study was supported by MSD Spain. Some of the authors declared receiving consulting fees, honoraria, travel expenses and/or research funding from various sources.

Source: Pérez-García JM et al. Eur J Cancer. 2021 Mar 29. doi: 10.1016/j.ejca.2021.02.028.

Key clinical point: Long-term data show similar local control rates with 10-Gy intraoperative electron radiotherapy (IOERT) vs. external beam radiotherapy (EBRT).

Major finding: The cumulative risk for in-breast true recurrences at 10 years was 4.3% after IOERT vs. 5.3% after EBRT boost (P = .493). The cumulative risk for out-field local recurrence at 10 years was 7.9% for IOERT vs. 10.3% for EBRT (P = .611).

Study details: Phase 3 randomized study of 245 patients with early-stage breast cancer who underwent breast-conserving surgery with either 10-Gy IOERT or EBRT boost.

Disclosures: An author received a study grant from IntraOp Medical. The authors declared no conflict of interests.

Source: Ciabattoni A et al. Breast Can Res. 2021 Apr 13. doi: 10.1186/s13058-021-01424-9.

Key clinical point: Long-term data show similar local control rates with 10-Gy intraoperative electron radiotherapy (IOERT) vs. external beam radiotherapy (EBRT).

Major finding: The cumulative risk for in-breast true recurrences at 10 years was 4.3% after IOERT vs. 5.3% after EBRT boost (P = .493). The cumulative risk for out-field local recurrence at 10 years was 7.9% for IOERT vs. 10.3% for EBRT (P = .611).

Study details: Phase 3 randomized study of 245 patients with early-stage breast cancer who underwent breast-conserving surgery with either 10-Gy IOERT or EBRT boost.

Disclosures: An author received a study grant from IntraOp Medical. The authors declared no conflict of interests.

Source: Ciabattoni A et al. Breast Can Res. 2021 Apr 13. doi: 10.1186/s13058-021-01424-9.

Key clinical point: Long-term data show similar local control rates with 10-Gy intraoperative electron radiotherapy (IOERT) vs. external beam radiotherapy (EBRT).

Major finding: The cumulative risk for in-breast true recurrences at 10 years was 4.3% after IOERT vs. 5.3% after EBRT boost (P = .493). The cumulative risk for out-field local recurrence at 10 years was 7.9% for IOERT vs. 10.3% for EBRT (P = .611).

Study details: Phase 3 randomized study of 245 patients with early-stage breast cancer who underwent breast-conserving surgery with either 10-Gy IOERT or EBRT boost.

Disclosures: An author received a study grant from IntraOp Medical. The authors declared no conflict of interests.

Source: Ciabattoni A et al. Breast Can Res. 2021 Apr 13. doi: 10.1186/s13058-021-01424-9.

Key clinical point: Sacituzumab govitecan improves survival vs. single-agent chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: Sacituzumab govitecan vs. chemotherapy showed 59% and 52% reduction in the risk for progression and mortality, respectively (P less than .001 for both). The objective response rate was 35% with sacituzumab govitecan and 5% with chemotherapy. Grade 3-4 adverse event rate was 64% and 47% in the sacituzumab govitecan and chemotherapy groups, respectively.

Study details: A phase 3 ASCENT study of patients with relapsed or refractory TNBC, randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: The study was supported by Immunomedics, a subsidiary of Gilead Sciences. The authors received consulting fees outside this work.

Source: Bardia A et al. New Eng J Med. 2021 Apr 22. doi: 10.1056/NEJMoa2028485.

Key clinical point: Sacituzumab govitecan improves survival vs. single-agent chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: Sacituzumab govitecan vs. chemotherapy showed 59% and 52% reduction in the risk for progression and mortality, respectively (P less than .001 for both). The objective response rate was 35% with sacituzumab govitecan and 5% with chemotherapy. Grade 3-4 adverse event rate was 64% and 47% in the sacituzumab govitecan and chemotherapy groups, respectively.

Study details: A phase 3 ASCENT study of patients with relapsed or refractory TNBC, randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: The study was supported by Immunomedics, a subsidiary of Gilead Sciences. The authors received consulting fees outside this work.

Source: Bardia A et al. New Eng J Med. 2021 Apr 22. doi: 10.1056/NEJMoa2028485.

Key clinical point: Sacituzumab govitecan improves survival vs. single-agent chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: Sacituzumab govitecan vs. chemotherapy showed 59% and 52% reduction in the risk for progression and mortality, respectively (P less than .001 for both). The objective response rate was 35% with sacituzumab govitecan and 5% with chemotherapy. Grade 3-4 adverse event rate was 64% and 47% in the sacituzumab govitecan and chemotherapy groups, respectively.

Study details: A phase 3 ASCENT study of patients with relapsed or refractory TNBC, randomly assigned to receive either sacituzumab govitecan or single-agent chemotherapy of physician’s choice.

Disclosures: The study was supported by Immunomedics, a subsidiary of Gilead Sciences. The authors received consulting fees outside this work.

Source: Bardia A et al. New Eng J Med. 2021 Apr 22. doi: 10.1056/NEJMoa2028485.

Hormonal therapies for the treatment of hormone-dependent breast and prostate cancer could raise the risk for myocardial infarction and stroke, and patients need to be closely monitored to allow early detection and treatment of cardiovascular disease (CVD), the American Heart Association says in a new scientific statement.
 

“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” Tochi Okwuosa, DO, chair of the writing group, said in a news release.

“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietitian, endocrinologist, and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” said Dr. Okwuosa, director of cardio-oncology services, Rush University Medical Center, Chicago.

The scientific statement was published online April 26 in Circulation: Genomic and Precision Medicine.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common noncutaneous cancers in the United States and around the world. As hormonal therapies have markedly improved survival in these patients, CVD has emerged as a leading cause illness and death.

The increased CVD burden might be explained by the increasing average age of cancer survivors, leading to higher rates of age-related CV risk factors and coronary artery disease.

The writing group reviewed existing evidence from observational studies and randomized controlled trials on the cardiovascular impact of anticancer hormonal therapies.



Among the key findings:

• In patients with breast cancer,  has been shown to increase the risk for venous thromboembolic events, but to have somewhat protective to neutral effects on CVD risk burden and CVD events. Conversely, aromatase inhibitors have been shown to increase the risk for CVD risk factors and events, including MI and stroke.
• Androgen-deprivation therapy for prostate cancer appears to increase the risk for CV events, although gonadotrophin-releasing hormone (GnRH) antagonists are associated with a lower risk for CV events than are GnRH agonists. The oral antiandrogens appear to be associated with increased CVD risk as well, particularly when used for complete androgen blockade as combination GnRH/anti-androgen therapy.
• The duration of hormonal therapies has a significant impact on CVD risk; the longer patients receive hormonal therapy, the greater the risk. More research is needed to better define the risks associated with duration of treatment.
• The data are mixed on the impact of preexisting CV risk factors and CVD on CV events associated with hormonal therapy. Although the presence of baseline CV risk factors and CVD can increase CV events associated with aromatase inhibitors, it is not clear that tamoxifen does.
• Studies suggest that patients with prostate cancer and baseline CVD and CV risk factors have increased rates of CV events when treated with androgen-deprivation therapy.
• Although the prolonged use of some hormonal therapies worsens CV risk factors and , the effects of the duration of therapy on CV events are less clear.

The writing group noted that there are no definitive guidelines for the monitoring and management of hormonal therapy-related CVD risks.

The authors encourage clinicians to be alert for worsening CV problems in those with preexisting heart disease or risk factors, and to recognize that even patients without preexisting CV problems are at higher risk because of their exposure to hormonal therapies.

“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Dr. Okwuosa said in the news release.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Council on Cardiovascular Radiology and Intervention.

The research had no commercial funding. Dr. Okwuosa has disclosed no relevant financial relationships.

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

Hormonal therapies for the treatment of hormone-dependent breast and prostate cancer could raise the risk for myocardial infarction and stroke, and patients need to be closely monitored to allow early detection and treatment of cardiovascular disease (CVD), the American Heart Association says in a new scientific statement.
 

“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” Tochi Okwuosa, DO, chair of the writing group, said in a news release.

“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietitian, endocrinologist, and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” said Dr. Okwuosa, director of cardio-oncology services, Rush University Medical Center, Chicago.

The scientific statement was published online April 26 in Circulation: Genomic and Precision Medicine.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common noncutaneous cancers in the United States and around the world. As hormonal therapies have markedly improved survival in these patients, CVD has emerged as a leading cause illness and death.

The increased CVD burden might be explained by the increasing average age of cancer survivors, leading to higher rates of age-related CV risk factors and coronary artery disease.

The writing group reviewed existing evidence from observational studies and randomized controlled trials on the cardiovascular impact of anticancer hormonal therapies.



Among the key findings:

• In patients with breast cancer,  has been shown to increase the risk for venous thromboembolic events, but to have somewhat protective to neutral effects on CVD risk burden and CVD events. Conversely, aromatase inhibitors have been shown to increase the risk for CVD risk factors and events, including MI and stroke.
• Androgen-deprivation therapy for prostate cancer appears to increase the risk for CV events, although gonadotrophin-releasing hormone (GnRH) antagonists are associated with a lower risk for CV events than are GnRH agonists. The oral antiandrogens appear to be associated with increased CVD risk as well, particularly when used for complete androgen blockade as combination GnRH/anti-androgen therapy.
• The duration of hormonal therapies has a significant impact on CVD risk; the longer patients receive hormonal therapy, the greater the risk. More research is needed to better define the risks associated with duration of treatment.
• The data are mixed on the impact of preexisting CV risk factors and CVD on CV events associated with hormonal therapy. Although the presence of baseline CV risk factors and CVD can increase CV events associated with aromatase inhibitors, it is not clear that tamoxifen does.
• Studies suggest that patients with prostate cancer and baseline CVD and CV risk factors have increased rates of CV events when treated with androgen-deprivation therapy.
• Although the prolonged use of some hormonal therapies worsens CV risk factors and , the effects of the duration of therapy on CV events are less clear.

The writing group noted that there are no definitive guidelines for the monitoring and management of hormonal therapy-related CVD risks.

The authors encourage clinicians to be alert for worsening CV problems in those with preexisting heart disease or risk factors, and to recognize that even patients without preexisting CV problems are at higher risk because of their exposure to hormonal therapies.

“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Dr. Okwuosa said in the news release.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Council on Cardiovascular Radiology and Intervention.

The research had no commercial funding. Dr. Okwuosa has disclosed no relevant financial relationships.

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

Hormonal therapies for the treatment of hormone-dependent breast and prostate cancer could raise the risk for myocardial infarction and stroke, and patients need to be closely monitored to allow early detection and treatment of cardiovascular disease (CVD), the American Heart Association says in a new scientific statement.
 

“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” Tochi Okwuosa, DO, chair of the writing group, said in a news release.

“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietitian, endocrinologist, and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” said Dr. Okwuosa, director of cardio-oncology services, Rush University Medical Center, Chicago.

The scientific statement was published online April 26 in Circulation: Genomic and Precision Medicine.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common noncutaneous cancers in the United States and around the world. As hormonal therapies have markedly improved survival in these patients, CVD has emerged as a leading cause illness and death.

The increased CVD burden might be explained by the increasing average age of cancer survivors, leading to higher rates of age-related CV risk factors and coronary artery disease.

The writing group reviewed existing evidence from observational studies and randomized controlled trials on the cardiovascular impact of anticancer hormonal therapies.



Among the key findings:

• In patients with breast cancer,  has been shown to increase the risk for venous thromboembolic events, but to have somewhat protective to neutral effects on CVD risk burden and CVD events. Conversely, aromatase inhibitors have been shown to increase the risk for CVD risk factors and events, including MI and stroke.
• Androgen-deprivation therapy for prostate cancer appears to increase the risk for CV events, although gonadotrophin-releasing hormone (GnRH) antagonists are associated with a lower risk for CV events than are GnRH agonists. The oral antiandrogens appear to be associated with increased CVD risk as well, particularly when used for complete androgen blockade as combination GnRH/anti-androgen therapy.
• The duration of hormonal therapies has a significant impact on CVD risk; the longer patients receive hormonal therapy, the greater the risk. More research is needed to better define the risks associated with duration of treatment.
• The data are mixed on the impact of preexisting CV risk factors and CVD on CV events associated with hormonal therapy. Although the presence of baseline CV risk factors and CVD can increase CV events associated with aromatase inhibitors, it is not clear that tamoxifen does.
• Studies suggest that patients with prostate cancer and baseline CVD and CV risk factors have increased rates of CV events when treated with androgen-deprivation therapy.
• Although the prolonged use of some hormonal therapies worsens CV risk factors and , the effects of the duration of therapy on CV events are less clear.

The writing group noted that there are no definitive guidelines for the monitoring and management of hormonal therapy-related CVD risks.

The authors encourage clinicians to be alert for worsening CV problems in those with preexisting heart disease or risk factors, and to recognize that even patients without preexisting CV problems are at higher risk because of their exposure to hormonal therapies.

“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Dr. Okwuosa said in the news release.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Council on Cardiovascular Radiology and Intervention.

The research had no commercial funding. Dr. Okwuosa has disclosed no relevant financial relationships.

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

On the first day of a historic 3-day meeting about drugs that were granted an accelerated approval by the Food and Drug Administration for cancer indications, the first approval to come under discussion is staying in place, at least for now.

Members of the FDA’s Oncologic Drugs Advisory Committee voted 7-2 in favor of keeping in place the indication for atezolizumab (Tecentriq) for use in a certain form of breast cancer. At the same time, the committee urged the manufacturer, Genentech, to do the research needed to prove the medicine works for these patients.

The specific indication is for atezolizumab as part of a combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors are PD-L1 positive.

The FDA granted accelerated approval in 2019 for this use of atezolizumab, expecting Genentech to produce more extensive evidence of this benefit. But so far, Genentech has not produced the data proving to the FDA that atezolizumab provides the expected benefit.

The drug was already available for use in bladder cancer, having been granted a full approval for this indication in 2016.
 

Other accelerated approvals withdrawn

This week’s 3-day ODAC meeting is part of the FDA’s broader reconsideration of what it has described as “dangling accelerated approvals.”

Earlier discussions between the FDA and drugmakers have already triggered four voluntary withdrawals of cancer indications with these accelerated approvals, noted Julia A. Beaver, MD, and Richard Pazdur, MD, two of the FDA’s top regulators of oncology medicine, in an April 21 perspective article in the New England Journal of Medicine.

“The small percentage of drugs whose clinical benefit is ultimately not confirmed should be viewed not as a failure of accelerated approval but rather as an expected trade-off in expediting drug development that benefits patients with severe or life-threatening diseases,” Dr. Beaver and Dr. Pazdur wrote.

But making these calls can be tough. On the first day of the meeting, even ODAC panelists who backed Genentech’s bid to maintain an mTNBC indication for atezolizumab expressed discomfort with this choice.

The FDA granted the accelerated approval for use of this drug in March 2019 based on improved progression-free survival from the IMpassion130 trial. But the drug fell short in subsequent efforts to confirm the results seen in that study. The confirmatory IMpassion131 trial failed to meet the primary endpoint, the FDA staff noted in briefing materials for the ODAC meeting.

ODAC panelist Stan Lipkowitz, MD, PhD, of the National Cancer Institute, said he expected this vote had been a tough one for all members serving on ODAC that day.

“In some ways, the purist in me said I should have voted no. But when I looked at the data, there are a couple of things that struck me,” said Dr. Lipkowitz, who is the chief of the Women’s Malignancies Branch at NCI’s Center for Cancer Research. “First of all, the landscape hasn’t changed. There’s really no therapy in the first line for triple-negative metastatic that is shown to improve survival.”

Dr. Lipkowitz emphasized that Genentech needs to continue to try to prove atezolizumab works in this setting.

“There needs to be confirmatory study,” Dr. Lipkowitz concluded.

ODAC panelist Matthew Ellis, MD, PhD, of Baylor College of Medicine, Houston, said he also understood the difficult outlook for women fighting this cancer, but he voted against maintaining the approval.

“It’s not that I don’t feel the tragedy of these women,” said Dr. Ellis, citing his own decades of clinical experience.

“I just think that the data are the data,” Dr. Ellis said, adding that, in his view, “the only correct interpretation” of the evidence supported a vote against allowing the indication to stay.

The FDA considers the recommendations of its advisory committees but is not bound by them.

In a statement issued after the vote, Genentech said it intends to work with the FDA to determine the next steps for this indication of atezolizumab because “the clinically meaningful benefit demonstrated in the IMpassion130 study remains.”

The ODAC meeting continues for 2 more days, and will consider five more cancer indications that have been granted an accelerated approval.

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

On the first day of a historic 3-day meeting about drugs that were granted an accelerated approval by the Food and Drug Administration for cancer indications, the first approval to come under discussion is staying in place, at least for now.

Members of the FDA’s Oncologic Drugs Advisory Committee voted 7-2 in favor of keeping in place the indication for atezolizumab (Tecentriq) for use in a certain form of breast cancer. At the same time, the committee urged the manufacturer, Genentech, to do the research needed to prove the medicine works for these patients.

The specific indication is for atezolizumab as part of a combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors are PD-L1 positive.

The FDA granted accelerated approval in 2019 for this use of atezolizumab, expecting Genentech to produce more extensive evidence of this benefit. But so far, Genentech has not produced the data proving to the FDA that atezolizumab provides the expected benefit.

The drug was already available for use in bladder cancer, having been granted a full approval for this indication in 2016.
 

Other accelerated approvals withdrawn

This week’s 3-day ODAC meeting is part of the FDA’s broader reconsideration of what it has described as “dangling accelerated approvals.”

Earlier discussions between the FDA and drugmakers have already triggered four voluntary withdrawals of cancer indications with these accelerated approvals, noted Julia A. Beaver, MD, and Richard Pazdur, MD, two of the FDA’s top regulators of oncology medicine, in an April 21 perspective article in the New England Journal of Medicine.

“The small percentage of drugs whose clinical benefit is ultimately not confirmed should be viewed not as a failure of accelerated approval but rather as an expected trade-off in expediting drug development that benefits patients with severe or life-threatening diseases,” Dr. Beaver and Dr. Pazdur wrote.

But making these calls can be tough. On the first day of the meeting, even ODAC panelists who backed Genentech’s bid to maintain an mTNBC indication for atezolizumab expressed discomfort with this choice.

The FDA granted the accelerated approval for use of this drug in March 2019 based on improved progression-free survival from the IMpassion130 trial. But the drug fell short in subsequent efforts to confirm the results seen in that study. The confirmatory IMpassion131 trial failed to meet the primary endpoint, the FDA staff noted in briefing materials for the ODAC meeting.

ODAC panelist Stan Lipkowitz, MD, PhD, of the National Cancer Institute, said he expected this vote had been a tough one for all members serving on ODAC that day.

“In some ways, the purist in me said I should have voted no. But when I looked at the data, there are a couple of things that struck me,” said Dr. Lipkowitz, who is the chief of the Women’s Malignancies Branch at NCI’s Center for Cancer Research. “First of all, the landscape hasn’t changed. There’s really no therapy in the first line for triple-negative metastatic that is shown to improve survival.”

Dr. Lipkowitz emphasized that Genentech needs to continue to try to prove atezolizumab works in this setting.

“There needs to be confirmatory study,” Dr. Lipkowitz concluded.

ODAC panelist Matthew Ellis, MD, PhD, of Baylor College of Medicine, Houston, said he also understood the difficult outlook for women fighting this cancer, but he voted against maintaining the approval.

“It’s not that I don’t feel the tragedy of these women,” said Dr. Ellis, citing his own decades of clinical experience.

“I just think that the data are the data,” Dr. Ellis said, adding that, in his view, “the only correct interpretation” of the evidence supported a vote against allowing the indication to stay.

The FDA considers the recommendations of its advisory committees but is not bound by them.

In a statement issued after the vote, Genentech said it intends to work with the FDA to determine the next steps for this indication of atezolizumab because “the clinically meaningful benefit demonstrated in the IMpassion130 study remains.”

The ODAC meeting continues for 2 more days, and will consider five more cancer indications that have been granted an accelerated approval.

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

On the first day of a historic 3-day meeting about drugs that were granted an accelerated approval by the Food and Drug Administration for cancer indications, the first approval to come under discussion is staying in place, at least for now.

Members of the FDA’s Oncologic Drugs Advisory Committee voted 7-2 in favor of keeping in place the indication for atezolizumab (Tecentriq) for use in a certain form of breast cancer. At the same time, the committee urged the manufacturer, Genentech, to do the research needed to prove the medicine works for these patients.

The specific indication is for atezolizumab as part of a combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors are PD-L1 positive.

The FDA granted accelerated approval in 2019 for this use of atezolizumab, expecting Genentech to produce more extensive evidence of this benefit. But so far, Genentech has not produced the data proving to the FDA that atezolizumab provides the expected benefit.

The drug was already available for use in bladder cancer, having been granted a full approval for this indication in 2016.
 

Other accelerated approvals withdrawn

This week’s 3-day ODAC meeting is part of the FDA’s broader reconsideration of what it has described as “dangling accelerated approvals.”

Earlier discussions between the FDA and drugmakers have already triggered four voluntary withdrawals of cancer indications with these accelerated approvals, noted Julia A. Beaver, MD, and Richard Pazdur, MD, two of the FDA’s top regulators of oncology medicine, in an April 21 perspective article in the New England Journal of Medicine.

“The small percentage of drugs whose clinical benefit is ultimately not confirmed should be viewed not as a failure of accelerated approval but rather as an expected trade-off in expediting drug development that benefits patients with severe or life-threatening diseases,” Dr. Beaver and Dr. Pazdur wrote.

But making these calls can be tough. On the first day of the meeting, even ODAC panelists who backed Genentech’s bid to maintain an mTNBC indication for atezolizumab expressed discomfort with this choice.

The FDA granted the accelerated approval for use of this drug in March 2019 based on improved progression-free survival from the IMpassion130 trial. But the drug fell short in subsequent efforts to confirm the results seen in that study. The confirmatory IMpassion131 trial failed to meet the primary endpoint, the FDA staff noted in briefing materials for the ODAC meeting.

ODAC panelist Stan Lipkowitz, MD, PhD, of the National Cancer Institute, said he expected this vote had been a tough one for all members serving on ODAC that day.

“In some ways, the purist in me said I should have voted no. But when I looked at the data, there are a couple of things that struck me,” said Dr. Lipkowitz, who is the chief of the Women’s Malignancies Branch at NCI’s Center for Cancer Research. “First of all, the landscape hasn’t changed. There’s really no therapy in the first line for triple-negative metastatic that is shown to improve survival.”

Dr. Lipkowitz emphasized that Genentech needs to continue to try to prove atezolizumab works in this setting.

“There needs to be confirmatory study,” Dr. Lipkowitz concluded.

ODAC panelist Matthew Ellis, MD, PhD, of Baylor College of Medicine, Houston, said he also understood the difficult outlook for women fighting this cancer, but he voted against maintaining the approval.

“It’s not that I don’t feel the tragedy of these women,” said Dr. Ellis, citing his own decades of clinical experience.

“I just think that the data are the data,” Dr. Ellis said, adding that, in his view, “the only correct interpretation” of the evidence supported a vote against allowing the indication to stay.

The FDA considers the recommendations of its advisory committees but is not bound by them.

In a statement issued after the vote, Genentech said it intends to work with the FDA to determine the next steps for this indication of atezolizumab because “the clinically meaningful benefit demonstrated in the IMpassion130 study remains.”

The ODAC meeting continues for 2 more days, and will consider five more cancer indications that have been granted an accelerated approval.

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

Combining plasma cell-free DNA (cfDNA) assessment with MRI improves prediction of pathological complete response to neoadjuvant chemotherapy in locally advanced breast cancer, according to researchers.

When the two techniques were in agreement, the accuracy of response prediction was 92.6% in the study, with a predictive value for complete response of 87.5% and a predictive value for absence of complete response of 94.7%, which was substantially better than either method alone.

“Our work identifies a new parameter that is easily combinable with MRI for a more accurate prediction of response following neoadjuvant treatment, with possible implications for current protocols for the evaluation of nodal residual disease,” researcher Francesco Ravera, MD, PhD, of the University of Genoa (Italy), said in a press release.

Dr. Ravera and colleagues presented their research in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract LB063).

Accurate response prediction is important because it guides subsequent surgical management, Dr. Ravera and colleagues noted. Pathological complete responders – generally about 25% of patients after neoadjuvant therapy – typically undergo a sentinel lymph node biopsy to ensure cancer hasn’t spread, while incomplete responders often have a complete axillary lymph node dissection.

Response is currently assessed by MRI, but accuracy is suboptimal, the researchers noted. A more accurate method might “allow the omission of sentinel lymph node biopsy in complete responders, which could be replaced by longitudinal radiologic monitoring. This would represent substantial progress in the pursuit of an effective, minimally invasive treatment,” Dr. Ravera said.

He and his colleagues turned to plasma cfDNA because it has shown potential for providing useful diagnostic, recurrence, and treatment response information in neoplastic patients.

When healthy cells die, they release similarly sized DNA fragments into the blood, but cancer cells release fragments of varying sizes. The heart of the research was using electrophoresis to assess the degree of fragmentation – called cfDNA integrity – in plasma samples from 38 patients after anthracycline/taxane-based regimens.

The researchers compared how well cfDNA, preoperative MRI, and the combination of the two methods predicted response according to surgical histology.

A total of 11 patients had pathological complete responses to neoadjuvant therapy.

The ratio of large 321-1,000 base pair sized fragments to smaller 150-220 base pair sized fragments, which the team dubbed the “cfDNA integrity index,” best predicted response. At a cutoff above 2.71, the index was 81.6% accurate in predicting pathological complete response, with a sensitivity of 81.8% and specificity of 81.5%.

The predictive power wasn’t much better than MRI, which was 77.1% accurate, with a sensitivity of 72.7% and a specificity of 81.5%.

The two techniques were concordant in their prediction in over two-thirds of patients. When the techniques agreed, accuracy was over 90%.

Prospective studies are needed to evaluate the cfDNA integrity index in combination with MRI, the researchers concluded.

The study was sponsored by the University of Genoa and others. Dr. Ravera disclosed no conflicts of interest.

[email protected]

Combining plasma cell-free DNA (cfDNA) assessment with MRI improves prediction of pathological complete response to neoadjuvant chemotherapy in locally advanced breast cancer, according to researchers.

When the two techniques were in agreement, the accuracy of response prediction was 92.6% in the study, with a predictive value for complete response of 87.5% and a predictive value for absence of complete response of 94.7%, which was substantially better than either method alone.

“Our work identifies a new parameter that is easily combinable with MRI for a more accurate prediction of response following neoadjuvant treatment, with possible implications for current protocols for the evaluation of nodal residual disease,” researcher Francesco Ravera, MD, PhD, of the University of Genoa (Italy), said in a press release.

Dr. Ravera and colleagues presented their research in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract LB063).

Accurate response prediction is important because it guides subsequent surgical management, Dr. Ravera and colleagues noted. Pathological complete responders – generally about 25% of patients after neoadjuvant therapy – typically undergo a sentinel lymph node biopsy to ensure cancer hasn’t spread, while incomplete responders often have a complete axillary lymph node dissection.

Response is currently assessed by MRI, but accuracy is suboptimal, the researchers noted. A more accurate method might “allow the omission of sentinel lymph node biopsy in complete responders, which could be replaced by longitudinal radiologic monitoring. This would represent substantial progress in the pursuit of an effective, minimally invasive treatment,” Dr. Ravera said.

He and his colleagues turned to plasma cfDNA because it has shown potential for providing useful diagnostic, recurrence, and treatment response information in neoplastic patients.

When healthy cells die, they release similarly sized DNA fragments into the blood, but cancer cells release fragments of varying sizes. The heart of the research was using electrophoresis to assess the degree of fragmentation – called cfDNA integrity – in plasma samples from 38 patients after anthracycline/taxane-based regimens.

The researchers compared how well cfDNA, preoperative MRI, and the combination of the two methods predicted response according to surgical histology.

A total of 11 patients had pathological complete responses to neoadjuvant therapy.

The ratio of large 321-1,000 base pair sized fragments to smaller 150-220 base pair sized fragments, which the team dubbed the “cfDNA integrity index,” best predicted response. At a cutoff above 2.71, the index was 81.6% accurate in predicting pathological complete response, with a sensitivity of 81.8% and specificity of 81.5%.

The predictive power wasn’t much better than MRI, which was 77.1% accurate, with a sensitivity of 72.7% and a specificity of 81.5%.

The two techniques were concordant in their prediction in over two-thirds of patients. When the techniques agreed, accuracy was over 90%.

Prospective studies are needed to evaluate the cfDNA integrity index in combination with MRI, the researchers concluded.

The study was sponsored by the University of Genoa and others. Dr. Ravera disclosed no conflicts of interest.

[email protected]

Combining plasma cell-free DNA (cfDNA) assessment with MRI improves prediction of pathological complete response to neoadjuvant chemotherapy in locally advanced breast cancer, according to researchers.

When the two techniques were in agreement, the accuracy of response prediction was 92.6% in the study, with a predictive value for complete response of 87.5% and a predictive value for absence of complete response of 94.7%, which was substantially better than either method alone.

“Our work identifies a new parameter that is easily combinable with MRI for a more accurate prediction of response following neoadjuvant treatment, with possible implications for current protocols for the evaluation of nodal residual disease,” researcher Francesco Ravera, MD, PhD, of the University of Genoa (Italy), said in a press release.

Dr. Ravera and colleagues presented their research in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract LB063).

Accurate response prediction is important because it guides subsequent surgical management, Dr. Ravera and colleagues noted. Pathological complete responders – generally about 25% of patients after neoadjuvant therapy – typically undergo a sentinel lymph node biopsy to ensure cancer hasn’t spread, while incomplete responders often have a complete axillary lymph node dissection.

Response is currently assessed by MRI, but accuracy is suboptimal, the researchers noted. A more accurate method might “allow the omission of sentinel lymph node biopsy in complete responders, which could be replaced by longitudinal radiologic monitoring. This would represent substantial progress in the pursuit of an effective, minimally invasive treatment,” Dr. Ravera said.

He and his colleagues turned to plasma cfDNA because it has shown potential for providing useful diagnostic, recurrence, and treatment response information in neoplastic patients.

When healthy cells die, they release similarly sized DNA fragments into the blood, but cancer cells release fragments of varying sizes. The heart of the research was using electrophoresis to assess the degree of fragmentation – called cfDNA integrity – in plasma samples from 38 patients after anthracycline/taxane-based regimens.

The researchers compared how well cfDNA, preoperative MRI, and the combination of the two methods predicted response according to surgical histology.

A total of 11 patients had pathological complete responses to neoadjuvant therapy.

The ratio of large 321-1,000 base pair sized fragments to smaller 150-220 base pair sized fragments, which the team dubbed the “cfDNA integrity index,” best predicted response. At a cutoff above 2.71, the index was 81.6% accurate in predicting pathological complete response, with a sensitivity of 81.8% and specificity of 81.5%.

The predictive power wasn’t much better than MRI, which was 77.1% accurate, with a sensitivity of 72.7% and a specificity of 81.5%.

The two techniques were concordant in their prediction in over two-thirds of patients. When the techniques agreed, accuracy was over 90%.

Prospective studies are needed to evaluate the cfDNA integrity index in combination with MRI, the researchers concluded.

The study was sponsored by the University of Genoa and others. Dr. Ravera disclosed no conflicts of interest.

[email protected]

Results from a phase 3 trial indicate that removing cyclophosphamide from standard chemotherapy can improve fertility without compromising survival in women with breast cancer.

Researchers found that omitting cyclophosphamide from a regimen of epirubicin and paclitaxel increased the likelihood of an early return of menses, and there was a trend toward improved disease-free survival.

The phase 3 SPECTRUM trial involved 521 women with estrogen receptor–positive, HER2-negative breast cancer who had undergone definitive surgery at one of eight institutions in China. The average age of the patients was 34 years.

Cyclophosphamide is a standard component of adjuvant chemotherapy, but it’s strongly associated with premature ovarian failure and infertility.

“For the first time, we demonstrate that a cyclophosphamide-free regimen [can] increase the rate of menses recovery without compromising survival,” said the researchers, led by Ke-Da Yu, MD, PhD, of the Fudan University Shanghai (China) Cancer Center.

They also reported that, among the women who tried to conceive at a later date, there was a higher pregnancy success rate among those who did not take cyclophosphamide.

“Our findings can be extrapolated to patients with other subtypes of breast cancer, such as triple-negative or HER2-enriched, because the effect of paclitaxel and cyclophosphamide on menstrual resumption is not subtype specific,” the investigators commented.

The results were published online in the Journal of the National Cancer Institute.

This is the first prospective trial specifically designed to find an adjuvant breast cancer regimen less toxic to the ovaries. The “investigators ... should be applauded,” wrote Matteo Lambertini, MD, PhD, of the University of Genova (Italy), and Ann Partridge, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

Although promising, there are a few caveats, the editorialists wrote. In a past trial of doxorubicin and docetaxel in lieu of a cyclophosphamide regimen, disease outcomes were inferior. There is also a question as to whether the SPECTRUM results apply to non-Asian women.

The editorialists also noted that enrollment in this trial ended in 2016, before it was recommended that ovarian suppression be used in conjunction with adjuvant chemotherapy to prevent premature menopause.

“[It’s] notable that the absolute benefit in reducing [premature ovarian insufficiency] rates with the use of a cyclophosphamide-free regimen is similar to the effect demonstrated with the administration of a gonadotropin-releasing hormone agonist during cyclophosphamide-based chemotherapy,” they commented. It’s possible that combining the two approaches might have an additive effect, but for now the possibility remains unknown.

In addition, the SPECTRUM trial predates the widespread use of genetic testing to guide treatment, the editorialists pointed out.

“Therefore, caution should be taken in adopting wholesale such regimens,” Dr. Lambertini and Dr. Partridge said.
 

Switch to paclitaxel

The research team was inspired by previous reports that swapping out cyclophosphamide for paclitaxel did not reduce adjuvant efficacy in the general breast cancer population.

The SPECTRUM trial randomly assigned 260 women to receive a cyclophosphamide-free regimen of epirubicin (75 mg/m²) and paclitaxel (175 mg/m²) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m²) for 12 weeks.

Another 261 women were randomly assigned to receive cyclophosphamide (600 mg/m²) and epirubicin (75 mg/m²) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m²) for 12 weeks. These patients constituted the control group.

A year after completing chemotherapy, 63.1% of the cyclophosphamide-free arm versus 48.3% of the control group, had resumed menses, defined as having two consecutive menstrual cycles or one cycle but with premenopausal levels of estradiol and follicle-stimulating hormone (P < .001).

Another caveat of the study is that assessments of women who resumed menses were conducted at the 1-year point; rates may have been higher in the cyclophosphamide arm had the investigators conducted the assessments at 2 years, the editorialists said.

The 5-year disease-free survival was 84.7% in the cyclophosphamide-free arm versus 78.3% in the control group, an absolute difference of 14.8% (P = .07).

Patients with node-positive disease appeared to benefit the most from cyclophosphamide sparing.

There were no statistically significant differences in overall or distant disease-free survival.
 

Higher pregnancy rates

Almost 18% of women in the experimental arm reported trying to conceive, and 9.6% of them did so. About 10% of women in the cyclophosphamide arm tried to conceive, and 2.7% did so (P = .03).

The median interval between randomization and pregnancy was 42 months.

For all of the women who became pregnant, endocrine therapy was interrupted. “Women who temporarily interrupt endocrine therapy due to pregnancy should be reminded to resume endocrine therapy following attempted or successful pregnancy,” the investigators wrote.

The patients were taking tamoxifen at least 5 years after receiving chemotherapy, most often as monotherapy. About 5% of the patients underwent up-front ovarian suppression with an aromatase inhibitor, which is a current standard option.

The study was supported by the National Natural Science Foundation of China and other organizations. The investigators and Dr. Partridge disclosed no relevant financial relationships. Dr. Lambertini has consulted for and/or has received speakers fees from Roche, AstraZeneca, Lilly, Novartis, and other companies.

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

Results from a phase 3 trial indicate that removing cyclophosphamide from standard chemotherapy can improve fertility without compromising survival in women with breast cancer.

Researchers found that omitting cyclophosphamide from a regimen of epirubicin and paclitaxel increased the likelihood of an early return of menses, and there was a trend toward improved disease-free survival.

The phase 3 SPECTRUM trial involved 521 women with estrogen receptor–positive, HER2-negative breast cancer who had undergone definitive surgery at one of eight institutions in China. The average age of the patients was 34 years.

Cyclophosphamide is a standard component of adjuvant chemotherapy, but it’s strongly associated with premature ovarian failure and infertility.

“For the first time, we demonstrate that a cyclophosphamide-free regimen [can] increase the rate of menses recovery without compromising survival,” said the researchers, led by Ke-Da Yu, MD, PhD, of the Fudan University Shanghai (China) Cancer Center.

They also reported that, among the women who tried to conceive at a later date, there was a higher pregnancy success rate among those who did not take cyclophosphamide.

“Our findings can be extrapolated to patients with other subtypes of breast cancer, such as triple-negative or HER2-enriched, because the effect of paclitaxel and cyclophosphamide on menstrual resumption is not subtype specific,” the investigators commented.

The results were published online in the Journal of the National Cancer Institute.

This is the first prospective trial specifically designed to find an adjuvant breast cancer regimen less toxic to the ovaries. The “investigators ... should be applauded,” wrote Matteo Lambertini, MD, PhD, of the University of Genova (Italy), and Ann Partridge, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

Although promising, there are a few caveats, the editorialists wrote. In a past trial of doxorubicin and docetaxel in lieu of a cyclophosphamide regimen, disease outcomes were inferior. There is also a question as to whether the SPECTRUM results apply to non-Asian women.

The editorialists also noted that enrollment in this trial ended in 2016, before it was recommended that ovarian suppression be used in conjunction with adjuvant chemotherapy to prevent premature menopause.

“[It’s] notable that the absolute benefit in reducing [premature ovarian insufficiency] rates with the use of a cyclophosphamide-free regimen is similar to the effect demonstrated with the administration of a gonadotropin-releasing hormone agonist during cyclophosphamide-based chemotherapy,” they commented. It’s possible that combining the two approaches might have an additive effect, but for now the possibility remains unknown.

In addition, the SPECTRUM trial predates the widespread use of genetic testing to guide treatment, the editorialists pointed out.

“Therefore, caution should be taken in adopting wholesale such regimens,” Dr. Lambertini and Dr. Partridge said.
 

Switch to paclitaxel

The research team was inspired by previous reports that swapping out cyclophosphamide for paclitaxel did not reduce adjuvant efficacy in the general breast cancer population.

The SPECTRUM trial randomly assigned 260 women to receive a cyclophosphamide-free regimen of epirubicin (75 mg/m²) and paclitaxel (175 mg/m²) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m²) for 12 weeks.

Another 261 women were randomly assigned to receive cyclophosphamide (600 mg/m²) and epirubicin (75 mg/m²) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m²) for 12 weeks. These patients constituted the control group.

A year after completing chemotherapy, 63.1% of the cyclophosphamide-free arm versus 48.3% of the control group, had resumed menses, defined as having two consecutive menstrual cycles or one cycle but with premenopausal levels of estradiol and follicle-stimulating hormone (P < .001).

Another caveat of the study is that assessments of women who resumed menses were conducted at the 1-year point; rates may have been higher in the cyclophosphamide arm had the investigators conducted the assessments at 2 years, the editorialists said.

The 5-year disease-free survival was 84.7% in the cyclophosphamide-free arm versus 78.3% in the control group, an absolute difference of 14.8% (P = .07).

Patients with node-positive disease appeared to benefit the most from cyclophosphamide sparing.

There were no statistically significant differences in overall or distant disease-free survival.
 

Higher pregnancy rates

Almost 18% of women in the experimental arm reported trying to conceive, and 9.6% of them did so. About 10% of women in the cyclophosphamide arm tried to conceive, and 2.7% did so (P = .03).

The median interval between randomization and pregnancy was 42 months.

For all of the women who became pregnant, endocrine therapy was interrupted. “Women who temporarily interrupt endocrine therapy due to pregnancy should be reminded to resume endocrine therapy following attempted or successful pregnancy,” the investigators wrote.

The patients were taking tamoxifen at least 5 years after receiving chemotherapy, most often as monotherapy. About 5% of the patients underwent up-front ovarian suppression with an aromatase inhibitor, which is a current standard option.

The study was supported by the National Natural Science Foundation of China and other organizations. The investigators and Dr. Partridge disclosed no relevant financial relationships. Dr. Lambertini has consulted for and/or has received speakers fees from Roche, AstraZeneca, Lilly, Novartis, and other companies.

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

Results from a phase 3 trial indicate that removing cyclophosphamide from standard chemotherapy can improve fertility without compromising survival in women with breast cancer.

Researchers found that omitting cyclophosphamide from a regimen of epirubicin and paclitaxel increased the likelihood of an early return of menses, and there was a trend toward improved disease-free survival.

The phase 3 SPECTRUM trial involved 521 women with estrogen receptor–positive, HER2-negative breast cancer who had undergone definitive surgery at one of eight institutions in China. The average age of the patients was 34 years.

Cyclophosphamide is a standard component of adjuvant chemotherapy, but it’s strongly associated with premature ovarian failure and infertility.

“For the first time, we demonstrate that a cyclophosphamide-free regimen [can] increase the rate of menses recovery without compromising survival,” said the researchers, led by Ke-Da Yu, MD, PhD, of the Fudan University Shanghai (China) Cancer Center.

They also reported that, among the women who tried to conceive at a later date, there was a higher pregnancy success rate among those who did not take cyclophosphamide.

“Our findings can be extrapolated to patients with other subtypes of breast cancer, such as triple-negative or HER2-enriched, because the effect of paclitaxel and cyclophosphamide on menstrual resumption is not subtype specific,” the investigators commented.

The results were published online in the Journal of the National Cancer Institute.

This is the first prospective trial specifically designed to find an adjuvant breast cancer regimen less toxic to the ovaries. The “investigators ... should be applauded,” wrote Matteo Lambertini, MD, PhD, of the University of Genova (Italy), and Ann Partridge, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

Although promising, there are a few caveats, the editorialists wrote. In a past trial of doxorubicin and docetaxel in lieu of a cyclophosphamide regimen, disease outcomes were inferior. There is also a question as to whether the SPECTRUM results apply to non-Asian women.

The editorialists also noted that enrollment in this trial ended in 2016, before it was recommended that ovarian suppression be used in conjunction with adjuvant chemotherapy to prevent premature menopause.

“[It’s] notable that the absolute benefit in reducing [premature ovarian insufficiency] rates with the use of a cyclophosphamide-free regimen is similar to the effect demonstrated with the administration of a gonadotropin-releasing hormone agonist during cyclophosphamide-based chemotherapy,” they commented. It’s possible that combining the two approaches might have an additive effect, but for now the possibility remains unknown.

In addition, the SPECTRUM trial predates the widespread use of genetic testing to guide treatment, the editorialists pointed out.

“Therefore, caution should be taken in adopting wholesale such regimens,” Dr. Lambertini and Dr. Partridge said.
 

Switch to paclitaxel

The research team was inspired by previous reports that swapping out cyclophosphamide for paclitaxel did not reduce adjuvant efficacy in the general breast cancer population.

The SPECTRUM trial randomly assigned 260 women to receive a cyclophosphamide-free regimen of epirubicin (75 mg/m²) and paclitaxel (175 mg/m²) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m²) for 12 weeks.

Another 261 women were randomly assigned to receive cyclophosphamide (600 mg/m²) and epirubicin (75 mg/m²) every 3 weeks for four cycles followed by weekly paclitaxel (80 mg/m²) for 12 weeks. These patients constituted the control group.

A year after completing chemotherapy, 63.1% of the cyclophosphamide-free arm versus 48.3% of the control group, had resumed menses, defined as having two consecutive menstrual cycles or one cycle but with premenopausal levels of estradiol and follicle-stimulating hormone (P < .001).

Another caveat of the study is that assessments of women who resumed menses were conducted at the 1-year point; rates may have been higher in the cyclophosphamide arm had the investigators conducted the assessments at 2 years, the editorialists said.

The 5-year disease-free survival was 84.7% in the cyclophosphamide-free arm versus 78.3% in the control group, an absolute difference of 14.8% (P = .07).

Patients with node-positive disease appeared to benefit the most from cyclophosphamide sparing.

There were no statistically significant differences in overall or distant disease-free survival.
 

Higher pregnancy rates

Almost 18% of women in the experimental arm reported trying to conceive, and 9.6% of them did so. About 10% of women in the cyclophosphamide arm tried to conceive, and 2.7% did so (P = .03).

The median interval between randomization and pregnancy was 42 months.

For all of the women who became pregnant, endocrine therapy was interrupted. “Women who temporarily interrupt endocrine therapy due to pregnancy should be reminded to resume endocrine therapy following attempted or successful pregnancy,” the investigators wrote.

The patients were taking tamoxifen at least 5 years after receiving chemotherapy, most often as monotherapy. About 5% of the patients underwent up-front ovarian suppression with an aromatase inhibitor, which is a current standard option.

The study was supported by the National Natural Science Foundation of China and other organizations. The investigators and Dr. Partridge disclosed no relevant financial relationships. Dr. Lambertini has consulted for and/or has received speakers fees from Roche, AstraZeneca, Lilly, Novartis, and other companies.

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

A personalized genomic cancer vaccine proved feasible to manufacture and was well tolerated in a phase 1 trial, according to researchers.

The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.

At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.

Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.

“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”

With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
 

Creating a personalized vaccine

The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.

Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.

OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
 

Vaccine administration

The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .

“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
 

Feasibility, safety, and immunogenicity

PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.

Eleven patients received all 10 intended doses, and two patients received at least 8 doses.

“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.

Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.

Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.

Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
 

Survival and subsequent therapy

At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.

Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.

Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.

“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.

Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.

The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.

A personalized genomic cancer vaccine proved feasible to manufacture and was well tolerated in a phase 1 trial, according to researchers.

The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.

At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.

Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.

“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”

With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
 

Creating a personalized vaccine

The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.

Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.

OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
 

Vaccine administration

The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .

“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
 

Feasibility, safety, and immunogenicity

PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.

Eleven patients received all 10 intended doses, and two patients received at least 8 doses.

“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.

Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.

Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.

Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
 

Survival and subsequent therapy

At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.

Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.

Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.

“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.

Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.

The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.

A personalized genomic cancer vaccine proved feasible to manufacture and was well tolerated in a phase 1 trial, according to researchers.

The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.

At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.

Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.

“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”

With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
 

Creating a personalized vaccine

The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.

Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.

OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
 

Vaccine administration

The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .

“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
 

Feasibility, safety, and immunogenicity

PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.

Eleven patients received all 10 intended doses, and two patients received at least 8 doses.

“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.

Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.

Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.

Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
 

Survival and subsequent therapy

At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.

Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.

Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.

“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.

Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.

The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.

The next 20 years will see a big shift in cancer type rankings, researchers predict.

At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.

By 2040, melanoma will have become the second most common cancer type, while prostate cancer will drop in incidence all the way to 14, the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.

These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.

The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.

Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.

“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.

The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.

The projected, estimated numbers are not ironclad, the researchers acknowledged.

“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.

“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.

Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.

“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
 

Difference in opinion on prostate cancer

The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.

“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.

“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.

Dr. Miller casts doubt on this prediction.

Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”

Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.

For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.

The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.

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

The next 20 years will see a big shift in cancer type rankings, researchers predict.

At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.

By 2040, melanoma will have become the second most common cancer type, while prostate cancer will drop in incidence all the way to 14, the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.

These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.

The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.

Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.

“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.

The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.

The projected, estimated numbers are not ironclad, the researchers acknowledged.

“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.

“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.

Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.

“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
 

Difference in opinion on prostate cancer

The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.

“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.

“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.

Dr. Miller casts doubt on this prediction.

Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”

Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.

For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.

The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.

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

The next 20 years will see a big shift in cancer type rankings, researchers predict.

At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.

By 2040, melanoma will have become the second most common cancer type, while prostate cancer will drop in incidence all the way to 14, the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.

These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.

The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.

Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.

“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.

The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.

The projected, estimated numbers are not ironclad, the researchers acknowledged.

“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.

“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.

Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.

“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
 

Difference in opinion on prostate cancer

The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.

“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.

“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.

Dr. Miller casts doubt on this prediction.

Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”

Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.

For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.

The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.

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