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Multigene testing for all patients with breast cancer may be cost-effective, life-saving
High-risk multigene testing for all patients with breast cancer may be a cost-effective way to reduce rates of breast cancer and ovarian cancer, according to investigators.
A microsimulation modeling study suggested that moving from standard BRCA testing based on clinical criteria or family history to widespread adoption of multigene testing could potentially save more than 2,400 lives per year in the United States, reported lead author Li Sun, MSc, of the London School of Hygiene & Tropical Medicine, and colleagues.
“Moving toward unselected BC testing may give an impetus for prevention in unaffected family members along with clinical implications for the patient with BC. Pathogenic variant carriers with newly diagnosed BC can opt for bilateral mastectomy rather than breast conservation at initial BC surgery,” the investigators wrote in JAMA Oncology. They noted that, presently, only 20%-30% of eligible patients are actually tested. “Testing all patients with breast cancer at diagnosis can increase testing access and uptake and identify many more pathogenic variant carriers for screening and prevention.”
To see if such a broad roll-out would be economically and medically feasible and beneficial, the investigators performed a modeling study involving 11,836 women with breast cancer, with data drawn from four large databases in the United Kingdom, the United States, and Australia.
The model compared annual costs, number of detected cases of breast cancer and ovarian cancer, and related rates of mortality between standard BRCA testing based on clinical criteria or family history versus high-risk multigene testing (BRCA1/BRCA2/PALB2) for all patients with breast cancer.
Resultant incremental cost-effectiveness ratios (ICERs) showed that in both the United Kingdom and the United States, multigene testing would cost, on average, significantly less than minimum willingness-to-pay thresholds of £30,000 per quality-adjusted life-year (QALY) and $100,000/QALY, respectively. In the United Kingdom, the estimated cost of multigene testing was £10,464/QALY from a payer’s perspective and £7,216/QALY from a societal perspective, the latter of which incorporates economic costs beyond the health care system. In the United States, these values rose to $65,661/QALY (payer perspective) and $61,618/QALY (societal perspective). Probabilistic sensitivity analysis suggested that multigene testing would be cost-effective for almost all health system simulations in the United Kingdom (98%-99%) and approximately two-thirds of those in the United States (64%-68%).
Epidemiologically, in the United Kingdom, multigene testing could potentially prevent 2,101 cases of breast cancer and ovarian cancer and 633 deaths per year, while in the United States, 9,733 cases might be prevented, with 2,406 lives saved.
“Our analysis suggests that an unselected testing strategy is extremely cost-effective for U.K. and U.S. health systems and provides a basis for change in current guidelines and policy to implement this strategy,” the investigators said.
The study was funded by the National Cancer Institute, the State of Washington, the Fred Hutchinson Cancer Research Center, and others. The investigators reported additional relationships with AstraZeneca, the Manchester National Institute for Health Research Biomedical Research Centre, Cancer Research UK, an others.
SOURCE: Sun et al. JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.3323.
Although detection of more pathogenic variants among patients with breast cancer may initially appear beneficial, the hidden risks and costs associated with broader multigene testing would likely outweigh the benefits.
Present guidelines, such as those provided by the National Comprehensive Cancer Network, already include effective strategies for detecting BRCA1/2 variants, as only 0.6% of patients who do not meet screening guidelines are estimated to test positive
Beyond BRCA1/2, the clinical relevance of pathogenic variants becomes dubious, as many genetic aberrations are not actionable. Furthermore, misinterpretation of unfamiliar results may increase risks of treatment decisions that might actually harm patients. While some argue that broader testing could have benefits for family members, this is poorly supported with evidence.
Behind the allegedly falling costs of genetic sequencing, true costs are hidden with corporate policies that reduce patient financial liability. It is worth noting that two publicly held testing companies recently reported annual revenues of $144 million and $498 million, representing money drawn largely from third-party payers covering guideline-recommended testing. Instead of concrete science, the popularity of multigene testing is more likely driven by active marketing and technological convenience. More independent studies are needed.
Mark Robson, MD, is with the department of breast cancer medicine and clinical genetics at Memorial Sloan Kettering Cancer Center in New York. Susan Domchek, MD is with the Basser Center for BRCA at the University of Pennsylvania in Philadelphia. Dr. Robson disclosed financial relationships with AstraZeneca, McKesson, and Pfizer. Dr. Domchek reported personal fees from Clovis, AstraZeneca, and BMS. Their remarks are adapted from an editorial (JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.4004).
Although detection of more pathogenic variants among patients with breast cancer may initially appear beneficial, the hidden risks and costs associated with broader multigene testing would likely outweigh the benefits.
Present guidelines, such as those provided by the National Comprehensive Cancer Network, already include effective strategies for detecting BRCA1/2 variants, as only 0.6% of patients who do not meet screening guidelines are estimated to test positive
Beyond BRCA1/2, the clinical relevance of pathogenic variants becomes dubious, as many genetic aberrations are not actionable. Furthermore, misinterpretation of unfamiliar results may increase risks of treatment decisions that might actually harm patients. While some argue that broader testing could have benefits for family members, this is poorly supported with evidence.
Behind the allegedly falling costs of genetic sequencing, true costs are hidden with corporate policies that reduce patient financial liability. It is worth noting that two publicly held testing companies recently reported annual revenues of $144 million and $498 million, representing money drawn largely from third-party payers covering guideline-recommended testing. Instead of concrete science, the popularity of multigene testing is more likely driven by active marketing and technological convenience. More independent studies are needed.
Mark Robson, MD, is with the department of breast cancer medicine and clinical genetics at Memorial Sloan Kettering Cancer Center in New York. Susan Domchek, MD is with the Basser Center for BRCA at the University of Pennsylvania in Philadelphia. Dr. Robson disclosed financial relationships with AstraZeneca, McKesson, and Pfizer. Dr. Domchek reported personal fees from Clovis, AstraZeneca, and BMS. Their remarks are adapted from an editorial (JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.4004).
Although detection of more pathogenic variants among patients with breast cancer may initially appear beneficial, the hidden risks and costs associated with broader multigene testing would likely outweigh the benefits.
Present guidelines, such as those provided by the National Comprehensive Cancer Network, already include effective strategies for detecting BRCA1/2 variants, as only 0.6% of patients who do not meet screening guidelines are estimated to test positive
Beyond BRCA1/2, the clinical relevance of pathogenic variants becomes dubious, as many genetic aberrations are not actionable. Furthermore, misinterpretation of unfamiliar results may increase risks of treatment decisions that might actually harm patients. While some argue that broader testing could have benefits for family members, this is poorly supported with evidence.
Behind the allegedly falling costs of genetic sequencing, true costs are hidden with corporate policies that reduce patient financial liability. It is worth noting that two publicly held testing companies recently reported annual revenues of $144 million and $498 million, representing money drawn largely from third-party payers covering guideline-recommended testing. Instead of concrete science, the popularity of multigene testing is more likely driven by active marketing and technological convenience. More independent studies are needed.
Mark Robson, MD, is with the department of breast cancer medicine and clinical genetics at Memorial Sloan Kettering Cancer Center in New York. Susan Domchek, MD is with the Basser Center for BRCA at the University of Pennsylvania in Philadelphia. Dr. Robson disclosed financial relationships with AstraZeneca, McKesson, and Pfizer. Dr. Domchek reported personal fees from Clovis, AstraZeneca, and BMS. Their remarks are adapted from an editorial (JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.4004).
High-risk multigene testing for all patients with breast cancer may be a cost-effective way to reduce rates of breast cancer and ovarian cancer, according to investigators.
A microsimulation modeling study suggested that moving from standard BRCA testing based on clinical criteria or family history to widespread adoption of multigene testing could potentially save more than 2,400 lives per year in the United States, reported lead author Li Sun, MSc, of the London School of Hygiene & Tropical Medicine, and colleagues.
“Moving toward unselected BC testing may give an impetus for prevention in unaffected family members along with clinical implications for the patient with BC. Pathogenic variant carriers with newly diagnosed BC can opt for bilateral mastectomy rather than breast conservation at initial BC surgery,” the investigators wrote in JAMA Oncology. They noted that, presently, only 20%-30% of eligible patients are actually tested. “Testing all patients with breast cancer at diagnosis can increase testing access and uptake and identify many more pathogenic variant carriers for screening and prevention.”
To see if such a broad roll-out would be economically and medically feasible and beneficial, the investigators performed a modeling study involving 11,836 women with breast cancer, with data drawn from four large databases in the United Kingdom, the United States, and Australia.
The model compared annual costs, number of detected cases of breast cancer and ovarian cancer, and related rates of mortality between standard BRCA testing based on clinical criteria or family history versus high-risk multigene testing (BRCA1/BRCA2/PALB2) for all patients with breast cancer.
Resultant incremental cost-effectiveness ratios (ICERs) showed that in both the United Kingdom and the United States, multigene testing would cost, on average, significantly less than minimum willingness-to-pay thresholds of £30,000 per quality-adjusted life-year (QALY) and $100,000/QALY, respectively. In the United Kingdom, the estimated cost of multigene testing was £10,464/QALY from a payer’s perspective and £7,216/QALY from a societal perspective, the latter of which incorporates economic costs beyond the health care system. In the United States, these values rose to $65,661/QALY (payer perspective) and $61,618/QALY (societal perspective). Probabilistic sensitivity analysis suggested that multigene testing would be cost-effective for almost all health system simulations in the United Kingdom (98%-99%) and approximately two-thirds of those in the United States (64%-68%).
Epidemiologically, in the United Kingdom, multigene testing could potentially prevent 2,101 cases of breast cancer and ovarian cancer and 633 deaths per year, while in the United States, 9,733 cases might be prevented, with 2,406 lives saved.
“Our analysis suggests that an unselected testing strategy is extremely cost-effective for U.K. and U.S. health systems and provides a basis for change in current guidelines and policy to implement this strategy,” the investigators said.
The study was funded by the National Cancer Institute, the State of Washington, the Fred Hutchinson Cancer Research Center, and others. The investigators reported additional relationships with AstraZeneca, the Manchester National Institute for Health Research Biomedical Research Centre, Cancer Research UK, an others.
SOURCE: Sun et al. JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.3323.
High-risk multigene testing for all patients with breast cancer may be a cost-effective way to reduce rates of breast cancer and ovarian cancer, according to investigators.
A microsimulation modeling study suggested that moving from standard BRCA testing based on clinical criteria or family history to widespread adoption of multigene testing could potentially save more than 2,400 lives per year in the United States, reported lead author Li Sun, MSc, of the London School of Hygiene & Tropical Medicine, and colleagues.
“Moving toward unselected BC testing may give an impetus for prevention in unaffected family members along with clinical implications for the patient with BC. Pathogenic variant carriers with newly diagnosed BC can opt for bilateral mastectomy rather than breast conservation at initial BC surgery,” the investigators wrote in JAMA Oncology. They noted that, presently, only 20%-30% of eligible patients are actually tested. “Testing all patients with breast cancer at diagnosis can increase testing access and uptake and identify many more pathogenic variant carriers for screening and prevention.”
To see if such a broad roll-out would be economically and medically feasible and beneficial, the investigators performed a modeling study involving 11,836 women with breast cancer, with data drawn from four large databases in the United Kingdom, the United States, and Australia.
The model compared annual costs, number of detected cases of breast cancer and ovarian cancer, and related rates of mortality between standard BRCA testing based on clinical criteria or family history versus high-risk multigene testing (BRCA1/BRCA2/PALB2) for all patients with breast cancer.
Resultant incremental cost-effectiveness ratios (ICERs) showed that in both the United Kingdom and the United States, multigene testing would cost, on average, significantly less than minimum willingness-to-pay thresholds of £30,000 per quality-adjusted life-year (QALY) and $100,000/QALY, respectively. In the United Kingdom, the estimated cost of multigene testing was £10,464/QALY from a payer’s perspective and £7,216/QALY from a societal perspective, the latter of which incorporates economic costs beyond the health care system. In the United States, these values rose to $65,661/QALY (payer perspective) and $61,618/QALY (societal perspective). Probabilistic sensitivity analysis suggested that multigene testing would be cost-effective for almost all health system simulations in the United Kingdom (98%-99%) and approximately two-thirds of those in the United States (64%-68%).
Epidemiologically, in the United Kingdom, multigene testing could potentially prevent 2,101 cases of breast cancer and ovarian cancer and 633 deaths per year, while in the United States, 9,733 cases might be prevented, with 2,406 lives saved.
“Our analysis suggests that an unselected testing strategy is extremely cost-effective for U.K. and U.S. health systems and provides a basis for change in current guidelines and policy to implement this strategy,” the investigators said.
The study was funded by the National Cancer Institute, the State of Washington, the Fred Hutchinson Cancer Research Center, and others. The investigators reported additional relationships with AstraZeneca, the Manchester National Institute for Health Research Biomedical Research Centre, Cancer Research UK, an others.
SOURCE: Sun et al. JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.3323.
FROM JAMA ONCOLOGY
Ribociclib/fulvestrant boosts survival in advanced breast cancer
BARCELONA – In postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer, the combination of ribociclib (Kisqali) and fulvestrant (Faslodex) was associated with a significant survival benefit, compared with fulvestrant alone, investigators reported.
Among 726 postmenopausal patients in MONALEESA-3 randomly assigned to receive either ribociclib or placebo plus fulvestrant who were followed for a median of 39.4 months, the median overall survival (OS) was not reached for patients assigned to ribociclib, compared with 40 months for patients in the control (fulvestrant-only) arm, reported Dennis J. Slamon, MD, PhD from the University of California, Los Angeles
“The combined data set of MONALEESA-3 and MONALEESA-7 represent some 1,400 patients, and the largest body of evidence for overall survival for any [cyclin-dependent kinases 4/6] inhibitor, and these data demonstrate a consistent, meaningful prolongation of survival irrespective of menopausal status, pre or post, and irrespective of whether the patient is treated in the first line or the second line,” he said at the European Society for Medical Oncology Congress.
Results of the MONALEESA-7 trial, which showed an overall survival advantage for adding ribociclib to endocrine therapy in premenopausal women with hormone receptor–positive, HER2-negative breast cancer, were reported at the 2019 annual meeting of the American Society of Clinical Oncology.
MONALEESA-3 investigators enrolled 726 postmenopausal women with hormone receptor–positive/HER2-negative advanced breast cancer who had received not more than one prior line of endocrine therapy for advanced disease, stratified them by the presence of liver and/or lung metastases and prior endocrine therapy, and then randomly assigned them to receive intramuscular fulvestrant 500 mg every 28 days, with an additional dose on day 15 of cycle one, plus either ribociclib 600 mg per day, 3 weeks on and 1 week off for every cycle, or placebo.
Dr. Slamon presented results of the primary endpoint of progression-free survival at the 2018 ASCO annual meeting, which showed a median PFS with ribociclib plus fulvestrant of 20.5 months versus 12.8 months for fulvestrant alone (hazard ratio, 5.93; P less than .0001). The overall survival data presented by Dr. Slamon at ESMO 2019 were not mature at that time.
As noted, at a median follow-up of 39.4 months, median overall survival was not reached in the combination arm, compared with 40 months in the fulvestrant/placebo arm, translating into a HR for risk of death with ribociclib of 0.724 (P = .00455).
Estimated OS rates at 36 months were 67% in the ribociclib arm versus 58.2% in the placebo arm, and at 42 months were 57.8% and 45.9%, respectively.
The survival benefit appeared consistent both for patients treated in the first line (median OS not reached vs. 45.1 months; HR, 0.70) and for those treated after early relapse of therapy for early breast or in the second line (median OS, 40.2 vs. 32.5 months, respectively; HR, 0.73). In both comparisons, however, the 95% confidence interval crossed 1, indicating that the results were not statistically significant.
An analysis of OS by subgroup indicated significant benefit or trends for most categories except Asian race, and treatment in Asia or Latin America, although the numbers of patients in each of those subgroups was less than 20, making it difficult to draw significant inferences from the findings, Dr. Slamon cautioned.
A descriptive analysis of updated PFS results were very similar to those previously reported, with a median of 20.6 months with ribociclib versus 12.8 months with placebo (HR, 0.587). Median PFS by line of therapy was 33.6 versus 19.2 months, respectively, in the first line, and 14.5 versus 9.1 months in the second line (HR, 0.546 and 0.571; P values not shown).
“CDK4/6 inhibitors not only improve progression-free survival in first- and second-line metastatic breast cancer, it also translates into an overall survival improvement. What more do we really want?” said invited discussant Sybil Loibl, MD, from Goethe University in Frankfurt, Germany.
“Outcome improves irrespective of pretreatment, menopausal status, endocrine sensitivity and site of metastases, which is good knowledge for our patients,” she said.
To date there are no biomarkers identified that can select subgroups that could experience particular benefit from CDK4/6 inhibitors. It may require a meta-analysis of all available clinical trial data on these agents in both the first and second line therapy to reveal potential differences among subgroups, she said.
MONALEESA-3 is supported by Novartis. Dr. Slamon disclosed a consulting or advisory role, research funding, honoraria, and travel expenses from Novartis and others. Dr. Loibl disclosed honoraria and research grants from Novartis and others.
SOURCE: Slamon DJ et al. ESMO 2019, Abstract LBA7_PR.
BARCELONA – In postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer, the combination of ribociclib (Kisqali) and fulvestrant (Faslodex) was associated with a significant survival benefit, compared with fulvestrant alone, investigators reported.
Among 726 postmenopausal patients in MONALEESA-3 randomly assigned to receive either ribociclib or placebo plus fulvestrant who were followed for a median of 39.4 months, the median overall survival (OS) was not reached for patients assigned to ribociclib, compared with 40 months for patients in the control (fulvestrant-only) arm, reported Dennis J. Slamon, MD, PhD from the University of California, Los Angeles
“The combined data set of MONALEESA-3 and MONALEESA-7 represent some 1,400 patients, and the largest body of evidence for overall survival for any [cyclin-dependent kinases 4/6] inhibitor, and these data demonstrate a consistent, meaningful prolongation of survival irrespective of menopausal status, pre or post, and irrespective of whether the patient is treated in the first line or the second line,” he said at the European Society for Medical Oncology Congress.
Results of the MONALEESA-7 trial, which showed an overall survival advantage for adding ribociclib to endocrine therapy in premenopausal women with hormone receptor–positive, HER2-negative breast cancer, were reported at the 2019 annual meeting of the American Society of Clinical Oncology.
MONALEESA-3 investigators enrolled 726 postmenopausal women with hormone receptor–positive/HER2-negative advanced breast cancer who had received not more than one prior line of endocrine therapy for advanced disease, stratified them by the presence of liver and/or lung metastases and prior endocrine therapy, and then randomly assigned them to receive intramuscular fulvestrant 500 mg every 28 days, with an additional dose on day 15 of cycle one, plus either ribociclib 600 mg per day, 3 weeks on and 1 week off for every cycle, or placebo.
Dr. Slamon presented results of the primary endpoint of progression-free survival at the 2018 ASCO annual meeting, which showed a median PFS with ribociclib plus fulvestrant of 20.5 months versus 12.8 months for fulvestrant alone (hazard ratio, 5.93; P less than .0001). The overall survival data presented by Dr. Slamon at ESMO 2019 were not mature at that time.
As noted, at a median follow-up of 39.4 months, median overall survival was not reached in the combination arm, compared with 40 months in the fulvestrant/placebo arm, translating into a HR for risk of death with ribociclib of 0.724 (P = .00455).
Estimated OS rates at 36 months were 67% in the ribociclib arm versus 58.2% in the placebo arm, and at 42 months were 57.8% and 45.9%, respectively.
The survival benefit appeared consistent both for patients treated in the first line (median OS not reached vs. 45.1 months; HR, 0.70) and for those treated after early relapse of therapy for early breast or in the second line (median OS, 40.2 vs. 32.5 months, respectively; HR, 0.73). In both comparisons, however, the 95% confidence interval crossed 1, indicating that the results were not statistically significant.
An analysis of OS by subgroup indicated significant benefit or trends for most categories except Asian race, and treatment in Asia or Latin America, although the numbers of patients in each of those subgroups was less than 20, making it difficult to draw significant inferences from the findings, Dr. Slamon cautioned.
A descriptive analysis of updated PFS results were very similar to those previously reported, with a median of 20.6 months with ribociclib versus 12.8 months with placebo (HR, 0.587). Median PFS by line of therapy was 33.6 versus 19.2 months, respectively, in the first line, and 14.5 versus 9.1 months in the second line (HR, 0.546 and 0.571; P values not shown).
“CDK4/6 inhibitors not only improve progression-free survival in first- and second-line metastatic breast cancer, it also translates into an overall survival improvement. What more do we really want?” said invited discussant Sybil Loibl, MD, from Goethe University in Frankfurt, Germany.
“Outcome improves irrespective of pretreatment, menopausal status, endocrine sensitivity and site of metastases, which is good knowledge for our patients,” she said.
To date there are no biomarkers identified that can select subgroups that could experience particular benefit from CDK4/6 inhibitors. It may require a meta-analysis of all available clinical trial data on these agents in both the first and second line therapy to reveal potential differences among subgroups, she said.
MONALEESA-3 is supported by Novartis. Dr. Slamon disclosed a consulting or advisory role, research funding, honoraria, and travel expenses from Novartis and others. Dr. Loibl disclosed honoraria and research grants from Novartis and others.
SOURCE: Slamon DJ et al. ESMO 2019, Abstract LBA7_PR.
BARCELONA – In postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer, the combination of ribociclib (Kisqali) and fulvestrant (Faslodex) was associated with a significant survival benefit, compared with fulvestrant alone, investigators reported.
Among 726 postmenopausal patients in MONALEESA-3 randomly assigned to receive either ribociclib or placebo plus fulvestrant who were followed for a median of 39.4 months, the median overall survival (OS) was not reached for patients assigned to ribociclib, compared with 40 months for patients in the control (fulvestrant-only) arm, reported Dennis J. Slamon, MD, PhD from the University of California, Los Angeles
“The combined data set of MONALEESA-3 and MONALEESA-7 represent some 1,400 patients, and the largest body of evidence for overall survival for any [cyclin-dependent kinases 4/6] inhibitor, and these data demonstrate a consistent, meaningful prolongation of survival irrespective of menopausal status, pre or post, and irrespective of whether the patient is treated in the first line or the second line,” he said at the European Society for Medical Oncology Congress.
Results of the MONALEESA-7 trial, which showed an overall survival advantage for adding ribociclib to endocrine therapy in premenopausal women with hormone receptor–positive, HER2-negative breast cancer, were reported at the 2019 annual meeting of the American Society of Clinical Oncology.
MONALEESA-3 investigators enrolled 726 postmenopausal women with hormone receptor–positive/HER2-negative advanced breast cancer who had received not more than one prior line of endocrine therapy for advanced disease, stratified them by the presence of liver and/or lung metastases and prior endocrine therapy, and then randomly assigned them to receive intramuscular fulvestrant 500 mg every 28 days, with an additional dose on day 15 of cycle one, plus either ribociclib 600 mg per day, 3 weeks on and 1 week off for every cycle, or placebo.
Dr. Slamon presented results of the primary endpoint of progression-free survival at the 2018 ASCO annual meeting, which showed a median PFS with ribociclib plus fulvestrant of 20.5 months versus 12.8 months for fulvestrant alone (hazard ratio, 5.93; P less than .0001). The overall survival data presented by Dr. Slamon at ESMO 2019 were not mature at that time.
As noted, at a median follow-up of 39.4 months, median overall survival was not reached in the combination arm, compared with 40 months in the fulvestrant/placebo arm, translating into a HR for risk of death with ribociclib of 0.724 (P = .00455).
Estimated OS rates at 36 months were 67% in the ribociclib arm versus 58.2% in the placebo arm, and at 42 months were 57.8% and 45.9%, respectively.
The survival benefit appeared consistent both for patients treated in the first line (median OS not reached vs. 45.1 months; HR, 0.70) and for those treated after early relapse of therapy for early breast or in the second line (median OS, 40.2 vs. 32.5 months, respectively; HR, 0.73). In both comparisons, however, the 95% confidence interval crossed 1, indicating that the results were not statistically significant.
An analysis of OS by subgroup indicated significant benefit or trends for most categories except Asian race, and treatment in Asia or Latin America, although the numbers of patients in each of those subgroups was less than 20, making it difficult to draw significant inferences from the findings, Dr. Slamon cautioned.
A descriptive analysis of updated PFS results were very similar to those previously reported, with a median of 20.6 months with ribociclib versus 12.8 months with placebo (HR, 0.587). Median PFS by line of therapy was 33.6 versus 19.2 months, respectively, in the first line, and 14.5 versus 9.1 months in the second line (HR, 0.546 and 0.571; P values not shown).
“CDK4/6 inhibitors not only improve progression-free survival in first- and second-line metastatic breast cancer, it also translates into an overall survival improvement. What more do we really want?” said invited discussant Sybil Loibl, MD, from Goethe University in Frankfurt, Germany.
“Outcome improves irrespective of pretreatment, menopausal status, endocrine sensitivity and site of metastases, which is good knowledge for our patients,” she said.
To date there are no biomarkers identified that can select subgroups that could experience particular benefit from CDK4/6 inhibitors. It may require a meta-analysis of all available clinical trial data on these agents in both the first and second line therapy to reveal potential differences among subgroups, she said.
MONALEESA-3 is supported by Novartis. Dr. Slamon disclosed a consulting or advisory role, research funding, honoraria, and travel expenses from Novartis and others. Dr. Loibl disclosed honoraria and research grants from Novartis and others.
SOURCE: Slamon DJ et al. ESMO 2019, Abstract LBA7_PR.
REPORTING FROM ESMO 2019
Cancer burden: Multiple metrics needed to clarify the big picture
A new analysis of 40 years of U.S. cancer data underscores the importance of looking at multiple metrics to discern the complex interplay of factors influencing cancer burden in the population. Findings showed that the epidemiologic signature – a composite of two or three key metrics – differed across cancer types and was favorable in some cases and unfavorable in others.
“Epidemiologic signatures that illustrate trends in population-based data on cancer burden provide insight into true cancer occurrence, overdiagnosis, and treatment advances,” explain the analysts, led by H. Gilbert Welch, MD, MPH, Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. “They are important indicators of the potential contribution of environmental exposures, primary preventive interventions, new treatments, and changing diagnostic and screening practices.”
Dr. Welch and colleagues analyzed data for the years 1975 through 2015, assessing juxtaposed trends in incidence, mortality, and, when available, metastatic incidence (cancer already metastatic at diagnosis) for 11 cancers individually and for all cancers combined. Incidence data combining invasive and in situ cancers were obtained from the original nine Surveillance, Epidemiology, and End Results (SEER) registries, and mortality data were obtained from the National Vital Statistics System.
The analysts then explored implications of the epidemiologic signatures as they pertain to true cancer occurrence (the underlying incidence of clinically meaningful cancer), overdiagnosis (detection of cancers that will not cause symptoms or death), and treatment advances.
Individual cancers
Findings of the analysis, published in a special report in the New England Journal of Medicine, revealed three broad categories of epidemiologic signatures having different implications for the public health and oncology fields.
Desirable signatures showed, for example, declining mortality against a backdrop of stable incidence over the 40-year period, signaling improved treatment, as seen for chronic myeloid leukemia following introduction of imatinib (Gleevec), according to the analysts. Lung cancer incidence and mortality rose and fell in tandem, reflecting an increase in smoking followed by a decrease in response to prevention efforts. Stomach, cervical, and colorectal cancers had both falling incidence – likely reflecting a true decline in occurrence related to prevention and/or screening detection and subsequent treatment of precancerous lesions – and falling mortality.
Undesirable signatures showed a rising incidence juxtaposed with stable mortality and stable or rising metastatic incidence, signaling likely overdiagnosis, Dr. Welch and colleagues proposed. Three cancers—thyroid cancer, kidney cancer, and melanoma—fell into this category; for thyroid cancer and melanoma, fairly recent upticks in metastatic incidence may reflect upstaging.
Finally, some signatures showed mixed signals, with rising incidence and falling mortality. Breast cancer incidence rose and stabilized, coinciding with introduction of screening mammography, and possibly reflecting an increase in true cancer occurrence or overdiagnosis (with stable metastatic incidence favoring the latter), the analysts speculate. Declining mortality since the 1990s may be due to improved treatment or screening, or both. Prostate cancer incidence rose sharply with introduction of prostate-specific antigen screening but then fell to initial levels, suggesting sensitivity of this cancer to diagnostic scrutiny. Falling metastatic incidence indicates screening leads to earlier diagnosis in some cases, while declining mortality starting in the 1990s may again reflect improved treatment or screening, or both.
All cancers
The epidemiologic signature for all cancers combined differed somewhat by sex. Women had a rising incidence during the 1980s that was mainly driven by lung and breast cancers, according to Dr. Welch and colleagues; a continued rise since the mid-1990s was largely driven by melanoma, kidney cancer, and thyroid cancer. Declining mortality since 1990 has been primarily due to reductions in deaths from breast and colorectal cancers, and, more recently, lung cancer.
Men had a “volatile pattern” in the incidence of all cancers combined that was attributable to prostate cancer trends; drops in lung and colorectal cancer incidences were offset by rises in melanoma and kidney cancer incidences, the analysts proposed. Declining mortality since 1990 was more marked than that among women and reflects a longer period of decline in lung cancer mortality, plus reductions in deaths from prostate cancer and colorectal cancer.
“Falling mortality means that there has been real progress against cancer in the past 40 years – largely reflecting improved treatment and the decline of a uniquely powerful causal factor: cigarette smoking,” Dr. Welch and colleagues noted. “The lack of an accompanying fall in incidence is an unfortunate side effect of early cancer-detection efforts.”
Dr. Welch reported that he had no relevant disclosures. The analysis did not receive any specific funding.
SOURCE: Welch HG et al. N Engl J Med. 2019;381:1378-86. doi: 10.1056/NEJMsr1905447.
A new analysis of 40 years of U.S. cancer data underscores the importance of looking at multiple metrics to discern the complex interplay of factors influencing cancer burden in the population. Findings showed that the epidemiologic signature – a composite of two or three key metrics – differed across cancer types and was favorable in some cases and unfavorable in others.
“Epidemiologic signatures that illustrate trends in population-based data on cancer burden provide insight into true cancer occurrence, overdiagnosis, and treatment advances,” explain the analysts, led by H. Gilbert Welch, MD, MPH, Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. “They are important indicators of the potential contribution of environmental exposures, primary preventive interventions, new treatments, and changing diagnostic and screening practices.”
Dr. Welch and colleagues analyzed data for the years 1975 through 2015, assessing juxtaposed trends in incidence, mortality, and, when available, metastatic incidence (cancer already metastatic at diagnosis) for 11 cancers individually and for all cancers combined. Incidence data combining invasive and in situ cancers were obtained from the original nine Surveillance, Epidemiology, and End Results (SEER) registries, and mortality data were obtained from the National Vital Statistics System.
The analysts then explored implications of the epidemiologic signatures as they pertain to true cancer occurrence (the underlying incidence of clinically meaningful cancer), overdiagnosis (detection of cancers that will not cause symptoms or death), and treatment advances.
Individual cancers
Findings of the analysis, published in a special report in the New England Journal of Medicine, revealed three broad categories of epidemiologic signatures having different implications for the public health and oncology fields.
Desirable signatures showed, for example, declining mortality against a backdrop of stable incidence over the 40-year period, signaling improved treatment, as seen for chronic myeloid leukemia following introduction of imatinib (Gleevec), according to the analysts. Lung cancer incidence and mortality rose and fell in tandem, reflecting an increase in smoking followed by a decrease in response to prevention efforts. Stomach, cervical, and colorectal cancers had both falling incidence – likely reflecting a true decline in occurrence related to prevention and/or screening detection and subsequent treatment of precancerous lesions – and falling mortality.
Undesirable signatures showed a rising incidence juxtaposed with stable mortality and stable or rising metastatic incidence, signaling likely overdiagnosis, Dr. Welch and colleagues proposed. Three cancers—thyroid cancer, kidney cancer, and melanoma—fell into this category; for thyroid cancer and melanoma, fairly recent upticks in metastatic incidence may reflect upstaging.
Finally, some signatures showed mixed signals, with rising incidence and falling mortality. Breast cancer incidence rose and stabilized, coinciding with introduction of screening mammography, and possibly reflecting an increase in true cancer occurrence or overdiagnosis (with stable metastatic incidence favoring the latter), the analysts speculate. Declining mortality since the 1990s may be due to improved treatment or screening, or both. Prostate cancer incidence rose sharply with introduction of prostate-specific antigen screening but then fell to initial levels, suggesting sensitivity of this cancer to diagnostic scrutiny. Falling metastatic incidence indicates screening leads to earlier diagnosis in some cases, while declining mortality starting in the 1990s may again reflect improved treatment or screening, or both.
All cancers
The epidemiologic signature for all cancers combined differed somewhat by sex. Women had a rising incidence during the 1980s that was mainly driven by lung and breast cancers, according to Dr. Welch and colleagues; a continued rise since the mid-1990s was largely driven by melanoma, kidney cancer, and thyroid cancer. Declining mortality since 1990 has been primarily due to reductions in deaths from breast and colorectal cancers, and, more recently, lung cancer.
Men had a “volatile pattern” in the incidence of all cancers combined that was attributable to prostate cancer trends; drops in lung and colorectal cancer incidences were offset by rises in melanoma and kidney cancer incidences, the analysts proposed. Declining mortality since 1990 was more marked than that among women and reflects a longer period of decline in lung cancer mortality, plus reductions in deaths from prostate cancer and colorectal cancer.
“Falling mortality means that there has been real progress against cancer in the past 40 years – largely reflecting improved treatment and the decline of a uniquely powerful causal factor: cigarette smoking,” Dr. Welch and colleagues noted. “The lack of an accompanying fall in incidence is an unfortunate side effect of early cancer-detection efforts.”
Dr. Welch reported that he had no relevant disclosures. The analysis did not receive any specific funding.
SOURCE: Welch HG et al. N Engl J Med. 2019;381:1378-86. doi: 10.1056/NEJMsr1905447.
A new analysis of 40 years of U.S. cancer data underscores the importance of looking at multiple metrics to discern the complex interplay of factors influencing cancer burden in the population. Findings showed that the epidemiologic signature – a composite of two or three key metrics – differed across cancer types and was favorable in some cases and unfavorable in others.
“Epidemiologic signatures that illustrate trends in population-based data on cancer burden provide insight into true cancer occurrence, overdiagnosis, and treatment advances,” explain the analysts, led by H. Gilbert Welch, MD, MPH, Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. “They are important indicators of the potential contribution of environmental exposures, primary preventive interventions, new treatments, and changing diagnostic and screening practices.”
Dr. Welch and colleagues analyzed data for the years 1975 through 2015, assessing juxtaposed trends in incidence, mortality, and, when available, metastatic incidence (cancer already metastatic at diagnosis) for 11 cancers individually and for all cancers combined. Incidence data combining invasive and in situ cancers were obtained from the original nine Surveillance, Epidemiology, and End Results (SEER) registries, and mortality data were obtained from the National Vital Statistics System.
The analysts then explored implications of the epidemiologic signatures as they pertain to true cancer occurrence (the underlying incidence of clinically meaningful cancer), overdiagnosis (detection of cancers that will not cause symptoms or death), and treatment advances.
Individual cancers
Findings of the analysis, published in a special report in the New England Journal of Medicine, revealed three broad categories of epidemiologic signatures having different implications for the public health and oncology fields.
Desirable signatures showed, for example, declining mortality against a backdrop of stable incidence over the 40-year period, signaling improved treatment, as seen for chronic myeloid leukemia following introduction of imatinib (Gleevec), according to the analysts. Lung cancer incidence and mortality rose and fell in tandem, reflecting an increase in smoking followed by a decrease in response to prevention efforts. Stomach, cervical, and colorectal cancers had both falling incidence – likely reflecting a true decline in occurrence related to prevention and/or screening detection and subsequent treatment of precancerous lesions – and falling mortality.
Undesirable signatures showed a rising incidence juxtaposed with stable mortality and stable or rising metastatic incidence, signaling likely overdiagnosis, Dr. Welch and colleagues proposed. Three cancers—thyroid cancer, kidney cancer, and melanoma—fell into this category; for thyroid cancer and melanoma, fairly recent upticks in metastatic incidence may reflect upstaging.
Finally, some signatures showed mixed signals, with rising incidence and falling mortality. Breast cancer incidence rose and stabilized, coinciding with introduction of screening mammography, and possibly reflecting an increase in true cancer occurrence or overdiagnosis (with stable metastatic incidence favoring the latter), the analysts speculate. Declining mortality since the 1990s may be due to improved treatment or screening, or both. Prostate cancer incidence rose sharply with introduction of prostate-specific antigen screening but then fell to initial levels, suggesting sensitivity of this cancer to diagnostic scrutiny. Falling metastatic incidence indicates screening leads to earlier diagnosis in some cases, while declining mortality starting in the 1990s may again reflect improved treatment or screening, or both.
All cancers
The epidemiologic signature for all cancers combined differed somewhat by sex. Women had a rising incidence during the 1980s that was mainly driven by lung and breast cancers, according to Dr. Welch and colleagues; a continued rise since the mid-1990s was largely driven by melanoma, kidney cancer, and thyroid cancer. Declining mortality since 1990 has been primarily due to reductions in deaths from breast and colorectal cancers, and, more recently, lung cancer.
Men had a “volatile pattern” in the incidence of all cancers combined that was attributable to prostate cancer trends; drops in lung and colorectal cancer incidences were offset by rises in melanoma and kidney cancer incidences, the analysts proposed. Declining mortality since 1990 was more marked than that among women and reflects a longer period of decline in lung cancer mortality, plus reductions in deaths from prostate cancer and colorectal cancer.
“Falling mortality means that there has been real progress against cancer in the past 40 years – largely reflecting improved treatment and the decline of a uniquely powerful causal factor: cigarette smoking,” Dr. Welch and colleagues noted. “The lack of an accompanying fall in incidence is an unfortunate side effect of early cancer-detection efforts.”
Dr. Welch reported that he had no relevant disclosures. The analysis did not receive any specific funding.
SOURCE: Welch HG et al. N Engl J Med. 2019;381:1378-86. doi: 10.1056/NEJMsr1905447.
FROM NEW ENGLAND JOURNAL OF MEDICINE
MONARCH 2: Abemaciclib plus fulvestrant improves overall survival
BARCELONA – Adding the CDK4/6 inhibitor abemaciclib to fulvestrant significantly improves overall survival in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer patients who progressed on prior endocrine therapy, according to findings from the phase 3 MONARCH 2 trial.
At a median follow-up of 47.7 months, overall survival – a secondary study endpoint – was 46.7 months in 446 patients randomized to receive abemaciclib and fulvestrant, compared with 37.3 months in 223 patients who received placebo and fulvestrant (hazard ratio, 0.757), George W. Sledge, MD, reported at the European Society for Medical Oncology Congress.
The overall survival benefit was consistent across stratification factors, which included site of metastasis (visceral, bone, or other) and resistance to prior endocrine therapy (primary versus secondary), but it was most pronounced in patients with visceral disease (HR, 0.675) and primary resistance to prior endocrine therapy (HR, 0.686), said Dr. Sledge, a professor of medicine at Stanford (Calif.) Medical Center.
Progression-free survival, the primary study endpoint, was 16.4 and 9.3 months at the previously reported 2-year follow-up in the treatment and placebo groups, respectively, and the current analysis showed progression-free survival to be “highly consistent” with those findings (16.9 vs. 9.3 months; HR, 0.563), he said.
“Of note, and of interest for further follow-up, a landmark analysis at 3 years shows that approximately three times as many patients on the abemaciclib arm remained progression free, compared to the control arm,” he added, also noting that time from randomization to postdiscontinuation chemotherapy was prolonged with abemaciclib, compared with placebo (50.2 vs. 22.1 months; HR, 0.625).
“A highly significant result,” he said.
At the 47.7 month follow-up, 17% and 4% of patients in the treatment and placebo groups, respectively, remained on treatment.
An additional exploratory analysis showed that 5.8% of patients receiving abemaciclib crossed over to another CDK4/6 inhibitor after discontinuation of therapy, compared with 17.0% of those in the placebo group.
“CDK4/6 inhibitors have emerged as standard-of-care treatment for patients with HR+, HER2– breast cancer,” he said, noting that abemaciclib is a selective CDK4/6 inhibitor with continuous, twice-daily oral administration. “It is approved for monotherapy after progression on endocrine therapy and prior chemotherapy in the metastatic setting, and ... in combination with endocrine therapy in the front-line setting and after progression.”
The global, randomized, double-blind MONARCH 2 trial assessed abemaciclib + fulvestrant in women with advanced endocrine therapy–resistant HR+, HER2– advanced breast cancer, including pre- or perimenopausal women with ovarian suppression and postmenopausal women.
Study participants were randomized 2:1 to receive 500 mg of fulvestrant per label instructions plus 150 mg of abemaciclib every 12 hours or placebo.
Treatment-emergent adverse events in MONARCH 2 were consistent with those previously reported in the primary analysis, Dr. Sledge said.
“Continued follow-up of MONARCH 2 is ongoing to further characterize the overall survival benefit and to look at exploratory efficacy and correlative endpoints,” he noted.
Speaking about the findings during a press conference at the meeting, Nadia Harbeck, MD, a professor at Ludwig Maximilians University, Munich, Germany, said they have important practice-changing implications.
“We were always struggling with whether to give these drugs first or second line, and I think now if we consider the first-line survival benefit ... [first-line use] should be standard of care,” she said, referring to CDK4/6 inhibitors and to findings from MONARCH 2 and prior studies of the inhibitors, including the MONALEESA-3 trial presented at the ESMO Congress.
MONALEESA-3 showed similar overall survival results with the CDK4/6 inhibitor ribociclib in postmenopausal women with HR+, HER2– advanced breast cancer.
“The data are highly clinically meaningful; I think they are going to make a huge impact on how we treat breast cancer,” Dr. Harbeck said.
Dr. Sledge has received trial support, research grants, and travel accommodations from Eli Lilly and Company; is a board member for Tessa Therapeutics; and is a consultant for Syndax, Symphogen, and Verseau Therapeutics. Dr. Harbeck disclosed financial relationships with Agendia, Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Genomic Health, Lilly, MSD, Nanostring, Novartis, Odonate, Pfizer, Roche, Sandoz/Hexal, and Seattle Genetics. She is also director of the West German Study Group and a member of the German AGO Breast Committee.
SOURCE: Sledge G et al., ESMO 2019, Abstract LBA6-PR.
BARCELONA – Adding the CDK4/6 inhibitor abemaciclib to fulvestrant significantly improves overall survival in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer patients who progressed on prior endocrine therapy, according to findings from the phase 3 MONARCH 2 trial.
At a median follow-up of 47.7 months, overall survival – a secondary study endpoint – was 46.7 months in 446 patients randomized to receive abemaciclib and fulvestrant, compared with 37.3 months in 223 patients who received placebo and fulvestrant (hazard ratio, 0.757), George W. Sledge, MD, reported at the European Society for Medical Oncology Congress.
The overall survival benefit was consistent across stratification factors, which included site of metastasis (visceral, bone, or other) and resistance to prior endocrine therapy (primary versus secondary), but it was most pronounced in patients with visceral disease (HR, 0.675) and primary resistance to prior endocrine therapy (HR, 0.686), said Dr. Sledge, a professor of medicine at Stanford (Calif.) Medical Center.
Progression-free survival, the primary study endpoint, was 16.4 and 9.3 months at the previously reported 2-year follow-up in the treatment and placebo groups, respectively, and the current analysis showed progression-free survival to be “highly consistent” with those findings (16.9 vs. 9.3 months; HR, 0.563), he said.
“Of note, and of interest for further follow-up, a landmark analysis at 3 years shows that approximately three times as many patients on the abemaciclib arm remained progression free, compared to the control arm,” he added, also noting that time from randomization to postdiscontinuation chemotherapy was prolonged with abemaciclib, compared with placebo (50.2 vs. 22.1 months; HR, 0.625).
“A highly significant result,” he said.
At the 47.7 month follow-up, 17% and 4% of patients in the treatment and placebo groups, respectively, remained on treatment.
An additional exploratory analysis showed that 5.8% of patients receiving abemaciclib crossed over to another CDK4/6 inhibitor after discontinuation of therapy, compared with 17.0% of those in the placebo group.
“CDK4/6 inhibitors have emerged as standard-of-care treatment for patients with HR+, HER2– breast cancer,” he said, noting that abemaciclib is a selective CDK4/6 inhibitor with continuous, twice-daily oral administration. “It is approved for monotherapy after progression on endocrine therapy and prior chemotherapy in the metastatic setting, and ... in combination with endocrine therapy in the front-line setting and after progression.”
The global, randomized, double-blind MONARCH 2 trial assessed abemaciclib + fulvestrant in women with advanced endocrine therapy–resistant HR+, HER2– advanced breast cancer, including pre- or perimenopausal women with ovarian suppression and postmenopausal women.
Study participants were randomized 2:1 to receive 500 mg of fulvestrant per label instructions plus 150 mg of abemaciclib every 12 hours or placebo.
Treatment-emergent adverse events in MONARCH 2 were consistent with those previously reported in the primary analysis, Dr. Sledge said.
“Continued follow-up of MONARCH 2 is ongoing to further characterize the overall survival benefit and to look at exploratory efficacy and correlative endpoints,” he noted.
Speaking about the findings during a press conference at the meeting, Nadia Harbeck, MD, a professor at Ludwig Maximilians University, Munich, Germany, said they have important practice-changing implications.
“We were always struggling with whether to give these drugs first or second line, and I think now if we consider the first-line survival benefit ... [first-line use] should be standard of care,” she said, referring to CDK4/6 inhibitors and to findings from MONARCH 2 and prior studies of the inhibitors, including the MONALEESA-3 trial presented at the ESMO Congress.
MONALEESA-3 showed similar overall survival results with the CDK4/6 inhibitor ribociclib in postmenopausal women with HR+, HER2– advanced breast cancer.
“The data are highly clinically meaningful; I think they are going to make a huge impact on how we treat breast cancer,” Dr. Harbeck said.
Dr. Sledge has received trial support, research grants, and travel accommodations from Eli Lilly and Company; is a board member for Tessa Therapeutics; and is a consultant for Syndax, Symphogen, and Verseau Therapeutics. Dr. Harbeck disclosed financial relationships with Agendia, Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Genomic Health, Lilly, MSD, Nanostring, Novartis, Odonate, Pfizer, Roche, Sandoz/Hexal, and Seattle Genetics. She is also director of the West German Study Group and a member of the German AGO Breast Committee.
SOURCE: Sledge G et al., ESMO 2019, Abstract LBA6-PR.
BARCELONA – Adding the CDK4/6 inhibitor abemaciclib to fulvestrant significantly improves overall survival in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer patients who progressed on prior endocrine therapy, according to findings from the phase 3 MONARCH 2 trial.
At a median follow-up of 47.7 months, overall survival – a secondary study endpoint – was 46.7 months in 446 patients randomized to receive abemaciclib and fulvestrant, compared with 37.3 months in 223 patients who received placebo and fulvestrant (hazard ratio, 0.757), George W. Sledge, MD, reported at the European Society for Medical Oncology Congress.
The overall survival benefit was consistent across stratification factors, which included site of metastasis (visceral, bone, or other) and resistance to prior endocrine therapy (primary versus secondary), but it was most pronounced in patients with visceral disease (HR, 0.675) and primary resistance to prior endocrine therapy (HR, 0.686), said Dr. Sledge, a professor of medicine at Stanford (Calif.) Medical Center.
Progression-free survival, the primary study endpoint, was 16.4 and 9.3 months at the previously reported 2-year follow-up in the treatment and placebo groups, respectively, and the current analysis showed progression-free survival to be “highly consistent” with those findings (16.9 vs. 9.3 months; HR, 0.563), he said.
“Of note, and of interest for further follow-up, a landmark analysis at 3 years shows that approximately three times as many patients on the abemaciclib arm remained progression free, compared to the control arm,” he added, also noting that time from randomization to postdiscontinuation chemotherapy was prolonged with abemaciclib, compared with placebo (50.2 vs. 22.1 months; HR, 0.625).
“A highly significant result,” he said.
At the 47.7 month follow-up, 17% and 4% of patients in the treatment and placebo groups, respectively, remained on treatment.
An additional exploratory analysis showed that 5.8% of patients receiving abemaciclib crossed over to another CDK4/6 inhibitor after discontinuation of therapy, compared with 17.0% of those in the placebo group.
“CDK4/6 inhibitors have emerged as standard-of-care treatment for patients with HR+, HER2– breast cancer,” he said, noting that abemaciclib is a selective CDK4/6 inhibitor with continuous, twice-daily oral administration. “It is approved for monotherapy after progression on endocrine therapy and prior chemotherapy in the metastatic setting, and ... in combination with endocrine therapy in the front-line setting and after progression.”
The global, randomized, double-blind MONARCH 2 trial assessed abemaciclib + fulvestrant in women with advanced endocrine therapy–resistant HR+, HER2– advanced breast cancer, including pre- or perimenopausal women with ovarian suppression and postmenopausal women.
Study participants were randomized 2:1 to receive 500 mg of fulvestrant per label instructions plus 150 mg of abemaciclib every 12 hours or placebo.
Treatment-emergent adverse events in MONARCH 2 were consistent with those previously reported in the primary analysis, Dr. Sledge said.
“Continued follow-up of MONARCH 2 is ongoing to further characterize the overall survival benefit and to look at exploratory efficacy and correlative endpoints,” he noted.
Speaking about the findings during a press conference at the meeting, Nadia Harbeck, MD, a professor at Ludwig Maximilians University, Munich, Germany, said they have important practice-changing implications.
“We were always struggling with whether to give these drugs first or second line, and I think now if we consider the first-line survival benefit ... [first-line use] should be standard of care,” she said, referring to CDK4/6 inhibitors and to findings from MONARCH 2 and prior studies of the inhibitors, including the MONALEESA-3 trial presented at the ESMO Congress.
MONALEESA-3 showed similar overall survival results with the CDK4/6 inhibitor ribociclib in postmenopausal women with HR+, HER2– advanced breast cancer.
“The data are highly clinically meaningful; I think they are going to make a huge impact on how we treat breast cancer,” Dr. Harbeck said.
Dr. Sledge has received trial support, research grants, and travel accommodations from Eli Lilly and Company; is a board member for Tessa Therapeutics; and is a consultant for Syndax, Symphogen, and Verseau Therapeutics. Dr. Harbeck disclosed financial relationships with Agendia, Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Genomic Health, Lilly, MSD, Nanostring, Novartis, Odonate, Pfizer, Roche, Sandoz/Hexal, and Seattle Genetics. She is also director of the West German Study Group and a member of the German AGO Breast Committee.
SOURCE: Sledge G et al., ESMO 2019, Abstract LBA6-PR.
REPORTING FROM ESMO 2019
Gene recurrence score helps predict successful combination therapy for early breast cancer
alone in a study of 1,389 women with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer.
“The 21-gene recurrence score (RS) assay provides prognostic information for distant recurrence in hormone-receptor–positive, ERBB2-negative early breast cancer that is independent of clinicopathologic features and is also predictive of chemotherapy benefit when the RS is high,” wrote Joseph A. Sparano, MD, of Montefiore Medical Center, New York, and his colleagues. However, little is known about how this risk score applies to women with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer, they said.
In the study published in JAMA Oncology, they identified 1,389 women with a recurrence score of 26-100 (the definition of a high recurrence risk). The average age of the patients was 56 years, and 71% were postmenopausal.
In addition to receiving endocrine therapy, the women were randomized to no chemotherapy (89 patients) or one of several chemotherapy regimens including docetaxel/cyclophosphamide (589 patients), anthracycline without a taxane (334 patients), an anthracycline and taxane (244 patients), cyclophosphamide/methotrexate/5-fluorouracil (52 patients), and other regimens (81 patients). Among those treated with chemotherapy, overall survival (OS) at 5 years was 96% and estimated rates of freedom from recurrence of breast cancer at a distant site, and from a distant and/or local regional site, at 5 years were 93% and 91%, respectively. At 5 years, the estimated rate of invasive disease–free survival (IDFS) was 88%.
When broken down by chemotherapy regimen, 5-year rates of freedom from recurrence of breast cancer at a distant site ranged from 92.3% to 95.5%, except for 88.5% for the cyclophosphamide/methotrexate/5-fluorouracil (CMF) group; the rate was 92.6% for patients in the no-chemotherapy group.
The 5-year rates of IDFS ranged from 84% to 91.3% in the chemotherapy groups, compared with 79.7% in the no-chemotherapy group.
The expected rates of distant recurrence in the overall patient population if treated with endocrine therapy alone was 78.8% at 5 years and 65.4% at 9 years, the researchers said. Rates among the patients with an RS of 26-30 if treated with endocrine therapy alone were 89.6% at 5 years and 80.6% at 9 years; rates for those with an RS of 31-100 were 70.7% and 54% for 5 and 9 years, respectively.
The study findings were limited by several factors including a lack of randomization to endocrine therapy alone and the relatively short follow-up period, the researchers noted. However, strengths include the large sample size and high rate of compliance with chemotherapy.
The results support data from previous studies and “add to the evidence base supporting the use of the 21-gene RS assay to guide the use of adjuvant chemotherapy in patients with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer,” they concluded.
The study was supported in part by the National Cancer Institute, the Canadian Cancer Society Research Institute, the Breast Cancer Research Foundation, the Komen Foundation, and the Breast Cancer Research Stamp issued by the United States Postal Service. Dr. Sparano disclosed grants from the National Cancer Institute. Of the remaining authors, several disclosed receiving personal or speaker fees from the assay manufacturer, Genomic Health; one author received funding from the company during the study.
SOURCE: Sparano J et al. JAMA Oncol. 2019 Sep 30. doi: 10.1001/jamaoncol.2019.4794.
alone in a study of 1,389 women with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer.
“The 21-gene recurrence score (RS) assay provides prognostic information for distant recurrence in hormone-receptor–positive, ERBB2-negative early breast cancer that is independent of clinicopathologic features and is also predictive of chemotherapy benefit when the RS is high,” wrote Joseph A. Sparano, MD, of Montefiore Medical Center, New York, and his colleagues. However, little is known about how this risk score applies to women with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer, they said.
In the study published in JAMA Oncology, they identified 1,389 women with a recurrence score of 26-100 (the definition of a high recurrence risk). The average age of the patients was 56 years, and 71% were postmenopausal.
In addition to receiving endocrine therapy, the women were randomized to no chemotherapy (89 patients) or one of several chemotherapy regimens including docetaxel/cyclophosphamide (589 patients), anthracycline without a taxane (334 patients), an anthracycline and taxane (244 patients), cyclophosphamide/methotrexate/5-fluorouracil (52 patients), and other regimens (81 patients). Among those treated with chemotherapy, overall survival (OS) at 5 years was 96% and estimated rates of freedom from recurrence of breast cancer at a distant site, and from a distant and/or local regional site, at 5 years were 93% and 91%, respectively. At 5 years, the estimated rate of invasive disease–free survival (IDFS) was 88%.
When broken down by chemotherapy regimen, 5-year rates of freedom from recurrence of breast cancer at a distant site ranged from 92.3% to 95.5%, except for 88.5% for the cyclophosphamide/methotrexate/5-fluorouracil (CMF) group; the rate was 92.6% for patients in the no-chemotherapy group.
The 5-year rates of IDFS ranged from 84% to 91.3% in the chemotherapy groups, compared with 79.7% in the no-chemotherapy group.
The expected rates of distant recurrence in the overall patient population if treated with endocrine therapy alone was 78.8% at 5 years and 65.4% at 9 years, the researchers said. Rates among the patients with an RS of 26-30 if treated with endocrine therapy alone were 89.6% at 5 years and 80.6% at 9 years; rates for those with an RS of 31-100 were 70.7% and 54% for 5 and 9 years, respectively.
The study findings were limited by several factors including a lack of randomization to endocrine therapy alone and the relatively short follow-up period, the researchers noted. However, strengths include the large sample size and high rate of compliance with chemotherapy.
The results support data from previous studies and “add to the evidence base supporting the use of the 21-gene RS assay to guide the use of adjuvant chemotherapy in patients with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer,” they concluded.
The study was supported in part by the National Cancer Institute, the Canadian Cancer Society Research Institute, the Breast Cancer Research Foundation, the Komen Foundation, and the Breast Cancer Research Stamp issued by the United States Postal Service. Dr. Sparano disclosed grants from the National Cancer Institute. Of the remaining authors, several disclosed receiving personal or speaker fees from the assay manufacturer, Genomic Health; one author received funding from the company during the study.
SOURCE: Sparano J et al. JAMA Oncol. 2019 Sep 30. doi: 10.1001/jamaoncol.2019.4794.
alone in a study of 1,389 women with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer.
“The 21-gene recurrence score (RS) assay provides prognostic information for distant recurrence in hormone-receptor–positive, ERBB2-negative early breast cancer that is independent of clinicopathologic features and is also predictive of chemotherapy benefit when the RS is high,” wrote Joseph A. Sparano, MD, of Montefiore Medical Center, New York, and his colleagues. However, little is known about how this risk score applies to women with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer, they said.
In the study published in JAMA Oncology, they identified 1,389 women with a recurrence score of 26-100 (the definition of a high recurrence risk). The average age of the patients was 56 years, and 71% were postmenopausal.
In addition to receiving endocrine therapy, the women were randomized to no chemotherapy (89 patients) or one of several chemotherapy regimens including docetaxel/cyclophosphamide (589 patients), anthracycline without a taxane (334 patients), an anthracycline and taxane (244 patients), cyclophosphamide/methotrexate/5-fluorouracil (52 patients), and other regimens (81 patients). Among those treated with chemotherapy, overall survival (OS) at 5 years was 96% and estimated rates of freedom from recurrence of breast cancer at a distant site, and from a distant and/or local regional site, at 5 years were 93% and 91%, respectively. At 5 years, the estimated rate of invasive disease–free survival (IDFS) was 88%.
When broken down by chemotherapy regimen, 5-year rates of freedom from recurrence of breast cancer at a distant site ranged from 92.3% to 95.5%, except for 88.5% for the cyclophosphamide/methotrexate/5-fluorouracil (CMF) group; the rate was 92.6% for patients in the no-chemotherapy group.
The 5-year rates of IDFS ranged from 84% to 91.3% in the chemotherapy groups, compared with 79.7% in the no-chemotherapy group.
The expected rates of distant recurrence in the overall patient population if treated with endocrine therapy alone was 78.8% at 5 years and 65.4% at 9 years, the researchers said. Rates among the patients with an RS of 26-30 if treated with endocrine therapy alone were 89.6% at 5 years and 80.6% at 9 years; rates for those with an RS of 31-100 were 70.7% and 54% for 5 and 9 years, respectively.
The study findings were limited by several factors including a lack of randomization to endocrine therapy alone and the relatively short follow-up period, the researchers noted. However, strengths include the large sample size and high rate of compliance with chemotherapy.
The results support data from previous studies and “add to the evidence base supporting the use of the 21-gene RS assay to guide the use of adjuvant chemotherapy in patients with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer,” they concluded.
The study was supported in part by the National Cancer Institute, the Canadian Cancer Society Research Institute, the Breast Cancer Research Foundation, the Komen Foundation, and the Breast Cancer Research Stamp issued by the United States Postal Service. Dr. Sparano disclosed grants from the National Cancer Institute. Of the remaining authors, several disclosed receiving personal or speaker fees from the assay manufacturer, Genomic Health; one author received funding from the company during the study.
SOURCE: Sparano J et al. JAMA Oncol. 2019 Sep 30. doi: 10.1001/jamaoncol.2019.4794.
FROM JAMA ONCOLOGY
Physicians not yet comfortable with using social media to recruit for trials
Social media presents some unique opportunities, as well as unique challenges, when it comes to being a tool for clinical trial recruitment.
Some of those opportunities and challenges were identified following interview with 44 physicians affiliated with the City of Hope Comprehensive Cancer Center in Duarte, Calif.
“There were three main themes identified by physicians as potential advantages of social media use for trial recruitment, as follows: increased visibility and awareness, improved communications, and patient engagement,” Mina Sedrak, MD, an oncologist at City of Hope, and colleagues wrote in JAMA Open Network.
“Most physicians cited social media as a useful platform to increase awareness and visibility of clinical trials, recognizing it as a means to reach large populations and easily spread information about available trials,” the authors wrote. “They described social media as a way to easily disseminate clinical trial information online to patients, caregivers, and other physicians because of the large number of users on these platform.”
The interviewed physicians also identified a number of disadvantages of using social media for clinical trial recruitment, including increased administrative burden, risk of misinformation, lack of guidance, and limited outreach.
Physicians expressed “apprehension about the potential of social media to oversimplify trials or spread misinformation” and “concerns that information might be misconstrued because of the nature of the Internet,” Dr. Sedrak and colleagues wrote.
Three themes were identified by physicians when prompted to talk about potential strategies for effectively using social media for clinical trial recruitment, including institutional support, evidence, training.
“Physicians expressed interest in using social media for recruitment if they were provided institutional resources to manage recruitment efforts on social media,” the authors noted. Physicians also called for the establishment of methodology to guide physicians on how to use social media as a recruitment tool. Third, they wanted more education on how to use social media as a recruitment tool.
Even as the context of these findings reveal the pros and cons, Dr. Sedrak and colleagues observed that “our findings revealed that physicians are not currently comfortable with or prepared to effectively use social media for cancer clinical trial recruitment. Although their are some aspects of these new modes of communication that physicians are enthusiastic about (i.e., increased visibility and awareness), several important concerns remain. Notably, many physicians felt uncomfortable with the idea of using social media because of increased administrative burden and concerns of the complexities of clinical trials would not be appropriately communicated.”
Authors noted the limitations of the research, particularly that all the interviewers were affiliated with the same cancer center and may not be generalizable to wider practice settings. It also did not include the perspective of nonphysician research personnel, who are more involved in the recruitment aspects.
“Further research is needed to address potential concerns that may arise in the future and gain a more comprehensive understanding of the risks and benefits that social media pose in clinical settings,” the authors noted. “Before social media can be integrated into clinical trials, specific guidelines must be defined for such use.”
They noted that the American Society of Clinical Oncology is working on such guidelines.
SOURCE: Sedark MS et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911528. doi: 10.1001/jamanetworkopen.2019.11528.
Social media presents some unique opportunities, as well as unique challenges, when it comes to being a tool for clinical trial recruitment.
Some of those opportunities and challenges were identified following interview with 44 physicians affiliated with the City of Hope Comprehensive Cancer Center in Duarte, Calif.
“There were three main themes identified by physicians as potential advantages of social media use for trial recruitment, as follows: increased visibility and awareness, improved communications, and patient engagement,” Mina Sedrak, MD, an oncologist at City of Hope, and colleagues wrote in JAMA Open Network.
“Most physicians cited social media as a useful platform to increase awareness and visibility of clinical trials, recognizing it as a means to reach large populations and easily spread information about available trials,” the authors wrote. “They described social media as a way to easily disseminate clinical trial information online to patients, caregivers, and other physicians because of the large number of users on these platform.”
The interviewed physicians also identified a number of disadvantages of using social media for clinical trial recruitment, including increased administrative burden, risk of misinformation, lack of guidance, and limited outreach.
Physicians expressed “apprehension about the potential of social media to oversimplify trials or spread misinformation” and “concerns that information might be misconstrued because of the nature of the Internet,” Dr. Sedrak and colleagues wrote.
Three themes were identified by physicians when prompted to talk about potential strategies for effectively using social media for clinical trial recruitment, including institutional support, evidence, training.
“Physicians expressed interest in using social media for recruitment if they were provided institutional resources to manage recruitment efforts on social media,” the authors noted. Physicians also called for the establishment of methodology to guide physicians on how to use social media as a recruitment tool. Third, they wanted more education on how to use social media as a recruitment tool.
Even as the context of these findings reveal the pros and cons, Dr. Sedrak and colleagues observed that “our findings revealed that physicians are not currently comfortable with or prepared to effectively use social media for cancer clinical trial recruitment. Although their are some aspects of these new modes of communication that physicians are enthusiastic about (i.e., increased visibility and awareness), several important concerns remain. Notably, many physicians felt uncomfortable with the idea of using social media because of increased administrative burden and concerns of the complexities of clinical trials would not be appropriately communicated.”
Authors noted the limitations of the research, particularly that all the interviewers were affiliated with the same cancer center and may not be generalizable to wider practice settings. It also did not include the perspective of nonphysician research personnel, who are more involved in the recruitment aspects.
“Further research is needed to address potential concerns that may arise in the future and gain a more comprehensive understanding of the risks and benefits that social media pose in clinical settings,” the authors noted. “Before social media can be integrated into clinical trials, specific guidelines must be defined for such use.”
They noted that the American Society of Clinical Oncology is working on such guidelines.
SOURCE: Sedark MS et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911528. doi: 10.1001/jamanetworkopen.2019.11528.
Social media presents some unique opportunities, as well as unique challenges, when it comes to being a tool for clinical trial recruitment.
Some of those opportunities and challenges were identified following interview with 44 physicians affiliated with the City of Hope Comprehensive Cancer Center in Duarte, Calif.
“There were three main themes identified by physicians as potential advantages of social media use for trial recruitment, as follows: increased visibility and awareness, improved communications, and patient engagement,” Mina Sedrak, MD, an oncologist at City of Hope, and colleagues wrote in JAMA Open Network.
“Most physicians cited social media as a useful platform to increase awareness and visibility of clinical trials, recognizing it as a means to reach large populations and easily spread information about available trials,” the authors wrote. “They described social media as a way to easily disseminate clinical trial information online to patients, caregivers, and other physicians because of the large number of users on these platform.”
The interviewed physicians also identified a number of disadvantages of using social media for clinical trial recruitment, including increased administrative burden, risk of misinformation, lack of guidance, and limited outreach.
Physicians expressed “apprehension about the potential of social media to oversimplify trials or spread misinformation” and “concerns that information might be misconstrued because of the nature of the Internet,” Dr. Sedrak and colleagues wrote.
Three themes were identified by physicians when prompted to talk about potential strategies for effectively using social media for clinical trial recruitment, including institutional support, evidence, training.
“Physicians expressed interest in using social media for recruitment if they were provided institutional resources to manage recruitment efforts on social media,” the authors noted. Physicians also called for the establishment of methodology to guide physicians on how to use social media as a recruitment tool. Third, they wanted more education on how to use social media as a recruitment tool.
Even as the context of these findings reveal the pros and cons, Dr. Sedrak and colleagues observed that “our findings revealed that physicians are not currently comfortable with or prepared to effectively use social media for cancer clinical trial recruitment. Although their are some aspects of these new modes of communication that physicians are enthusiastic about (i.e., increased visibility and awareness), several important concerns remain. Notably, many physicians felt uncomfortable with the idea of using social media because of increased administrative burden and concerns of the complexities of clinical trials would not be appropriately communicated.”
Authors noted the limitations of the research, particularly that all the interviewers were affiliated with the same cancer center and may not be generalizable to wider practice settings. It also did not include the perspective of nonphysician research personnel, who are more involved in the recruitment aspects.
“Further research is needed to address potential concerns that may arise in the future and gain a more comprehensive understanding of the risks and benefits that social media pose in clinical settings,” the authors noted. “Before social media can be integrated into clinical trials, specific guidelines must be defined for such use.”
They noted that the American Society of Clinical Oncology is working on such guidelines.
SOURCE: Sedark MS et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911528. doi: 10.1001/jamanetworkopen.2019.11528.
FROM JAMA OPEN NETWORK
AF risk is elevated after early-stage breast cancer diagnosis
Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.
“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”
The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.
An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.
Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.
At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.
Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).
Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.
“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.
“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.
Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.
SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.
Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.
“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”
The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.
An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.
Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.
At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.
Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).
Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.
“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.
“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.
Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.
SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.
Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.
“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”
The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.
An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.
Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.
At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.
Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).
Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.
“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.
“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.
Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.
SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.
FROM JAMA NETWORK OPEN
Mortality after breast cancer diagnosis found higher for men
Sex predicts mortality after a breast cancer diagnosis, with male patients about one-fifth more likely than female counterparts to have died by the 5-year mark, finds a cohort study of more than 1.8 million patients. Clinical characteristics and undertreatment explained much, but not all, of this excess mortality.
“Studies have indicated that male patients with breast cancer had worse overall survival than their female counterparts, including those with early-stage disease, although results have been inconsistent,” the investigators note. However, “few studies have systematically investigated the factors associated with mortality in male patients with breast cancer or assessed whether breast cancer prognosis for men is congruent with that for women, accounting for the differences in clinical characteristics and treatment.”
Senior investigator Xiao-Ou Shu, MD, PhD, of the Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tenn., and coinvestigators conducted a nationwide, registry-based cohort study using the National Cancer Database to identify patients receiving a breast cancer diagnosis during 2004-2014. Analyses were based on 16,025 male patients (mean age, 63.3 years) having a median follow-up of 54.0 months and 1,800,708 female patients (mean age, 59.9 years) having a median follow-up of 60.5 months.
Results reported in JAMA Oncology showed that men had higher mortality across all stages (P less than .001 for each). Male patients also had poorer relative overall survival (45.8% vs. 60.4%, P less than .001), 3-year survival (86.4% vs. 91.7%, P less than .001), and 5-year survival (77.6% vs. 86.4%, P less than .001).
Age, clinical factors (tumor size; nodal status; stage, ER, PR, and HER2 statuses; histologic type; grade; lymphovascular invasion; OncotypeDX Breast Recurrence Score; and Charlson/Deyo score), and treatment factors (surgical procedure, chemotherapy, endocrine therapy, radiation therapy, and immunotherapy) collectively explained 63.3% of the excess mortality rate for male patients. They explained fully 66.0% of the excess mortality in the first 3 years after diagnosis, including 30.5% and 13.6% of that among patients with stage I and stage II disease, respectively.
However, even after adjustment for these factors plus race/ethnicity and access to care, men still had significantly higher risks of overall mortality (adjusted hazard ratio, 1.19), 3-year mortality (adjusted hazard ratio, 1.15), and 5-year mortality (adjusted hazard ratio, 1.19).
The database used did not contain information on causes of death or on cancer recurrence or progression events, precluding analyses of disease-free survival.
“Future research should focus on why and how clinical characteristics, as well as biological features, may have different implications for the survival of male and female patients with breast cancer,” Dr. Shu and coinvestigators recommended. “Additional factors, particularly compliance to treatment, biological attributes, and lifestyle factors (e.g., smoking, drinking, and obesity), should be assessed to help in developing treatments tailored for men, which would mitigate this sex-based disparity.”
Dr. Shu disclosed no relevant conflicts of interest. One author was funded by the program of the China Scholarship Council.
SOURCE: Wang F et al. JAMA Oncol. 2019 Sep 19. doi: 10.1001/jamaoncol.2019.2803.
Sex predicts mortality after a breast cancer diagnosis, with male patients about one-fifth more likely than female counterparts to have died by the 5-year mark, finds a cohort study of more than 1.8 million patients. Clinical characteristics and undertreatment explained much, but not all, of this excess mortality.
“Studies have indicated that male patients with breast cancer had worse overall survival than their female counterparts, including those with early-stage disease, although results have been inconsistent,” the investigators note. However, “few studies have systematically investigated the factors associated with mortality in male patients with breast cancer or assessed whether breast cancer prognosis for men is congruent with that for women, accounting for the differences in clinical characteristics and treatment.”
Senior investigator Xiao-Ou Shu, MD, PhD, of the Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tenn., and coinvestigators conducted a nationwide, registry-based cohort study using the National Cancer Database to identify patients receiving a breast cancer diagnosis during 2004-2014. Analyses were based on 16,025 male patients (mean age, 63.3 years) having a median follow-up of 54.0 months and 1,800,708 female patients (mean age, 59.9 years) having a median follow-up of 60.5 months.
Results reported in JAMA Oncology showed that men had higher mortality across all stages (P less than .001 for each). Male patients also had poorer relative overall survival (45.8% vs. 60.4%, P less than .001), 3-year survival (86.4% vs. 91.7%, P less than .001), and 5-year survival (77.6% vs. 86.4%, P less than .001).
Age, clinical factors (tumor size; nodal status; stage, ER, PR, and HER2 statuses; histologic type; grade; lymphovascular invasion; OncotypeDX Breast Recurrence Score; and Charlson/Deyo score), and treatment factors (surgical procedure, chemotherapy, endocrine therapy, radiation therapy, and immunotherapy) collectively explained 63.3% of the excess mortality rate for male patients. They explained fully 66.0% of the excess mortality in the first 3 years after diagnosis, including 30.5% and 13.6% of that among patients with stage I and stage II disease, respectively.
However, even after adjustment for these factors plus race/ethnicity and access to care, men still had significantly higher risks of overall mortality (adjusted hazard ratio, 1.19), 3-year mortality (adjusted hazard ratio, 1.15), and 5-year mortality (adjusted hazard ratio, 1.19).
The database used did not contain information on causes of death or on cancer recurrence or progression events, precluding analyses of disease-free survival.
“Future research should focus on why and how clinical characteristics, as well as biological features, may have different implications for the survival of male and female patients with breast cancer,” Dr. Shu and coinvestigators recommended. “Additional factors, particularly compliance to treatment, biological attributes, and lifestyle factors (e.g., smoking, drinking, and obesity), should be assessed to help in developing treatments tailored for men, which would mitigate this sex-based disparity.”
Dr. Shu disclosed no relevant conflicts of interest. One author was funded by the program of the China Scholarship Council.
SOURCE: Wang F et al. JAMA Oncol. 2019 Sep 19. doi: 10.1001/jamaoncol.2019.2803.
Sex predicts mortality after a breast cancer diagnosis, with male patients about one-fifth more likely than female counterparts to have died by the 5-year mark, finds a cohort study of more than 1.8 million patients. Clinical characteristics and undertreatment explained much, but not all, of this excess mortality.
“Studies have indicated that male patients with breast cancer had worse overall survival than their female counterparts, including those with early-stage disease, although results have been inconsistent,” the investigators note. However, “few studies have systematically investigated the factors associated with mortality in male patients with breast cancer or assessed whether breast cancer prognosis for men is congruent with that for women, accounting for the differences in clinical characteristics and treatment.”
Senior investigator Xiao-Ou Shu, MD, PhD, of the Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tenn., and coinvestigators conducted a nationwide, registry-based cohort study using the National Cancer Database to identify patients receiving a breast cancer diagnosis during 2004-2014. Analyses were based on 16,025 male patients (mean age, 63.3 years) having a median follow-up of 54.0 months and 1,800,708 female patients (mean age, 59.9 years) having a median follow-up of 60.5 months.
Results reported in JAMA Oncology showed that men had higher mortality across all stages (P less than .001 for each). Male patients also had poorer relative overall survival (45.8% vs. 60.4%, P less than .001), 3-year survival (86.4% vs. 91.7%, P less than .001), and 5-year survival (77.6% vs. 86.4%, P less than .001).
Age, clinical factors (tumor size; nodal status; stage, ER, PR, and HER2 statuses; histologic type; grade; lymphovascular invasion; OncotypeDX Breast Recurrence Score; and Charlson/Deyo score), and treatment factors (surgical procedure, chemotherapy, endocrine therapy, radiation therapy, and immunotherapy) collectively explained 63.3% of the excess mortality rate for male patients. They explained fully 66.0% of the excess mortality in the first 3 years after diagnosis, including 30.5% and 13.6% of that among patients with stage I and stage II disease, respectively.
However, even after adjustment for these factors plus race/ethnicity and access to care, men still had significantly higher risks of overall mortality (adjusted hazard ratio, 1.19), 3-year mortality (adjusted hazard ratio, 1.15), and 5-year mortality (adjusted hazard ratio, 1.19).
The database used did not contain information on causes of death or on cancer recurrence or progression events, precluding analyses of disease-free survival.
“Future research should focus on why and how clinical characteristics, as well as biological features, may have different implications for the survival of male and female patients with breast cancer,” Dr. Shu and coinvestigators recommended. “Additional factors, particularly compliance to treatment, biological attributes, and lifestyle factors (e.g., smoking, drinking, and obesity), should be assessed to help in developing treatments tailored for men, which would mitigate this sex-based disparity.”
Dr. Shu disclosed no relevant conflicts of interest. One author was funded by the program of the China Scholarship Council.
SOURCE: Wang F et al. JAMA Oncol. 2019 Sep 19. doi: 10.1001/jamaoncol.2019.2803.
FROM JAMA ONCOLOGY
Meta-analysis supports hormone therapy-targeted therapy combo for advanced breast cancer
Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.
Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.
The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.
Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.
Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.
“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”
For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.
Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).
Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).
When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.
For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).
Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.
SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.
“This meta-analysis solidifies an increasingly accepted role for CDK4/6 inhibitors in the upfront treatment of postmenopausal women with hormone receptor–positive, HER2-negative metastatic breast cancer,” Azadeh Nasrazadani, PhD, MD, and Adam M. Brufsky, MD, PhD, wrote in an editorial published in Lancet Oncology. “These agents are starting to displace more toxic chemotherapy agents as frontline treatments for estrogen receptor–positive metastatic breast cancer in general practice because of, to some extent, their similar efficacy with substantially more favorable side-effect profiles.”
Nonetheless, chemotherapy still has a role in this population, typically in the later-line setting and in patients experiencing a visceral crisis, they noted. However, the better overall response rate seen with a chemotherapy regimen (paclitaxel plus bevacizumab), compared with a combination targeted and hormonal therapy regimen (palbociclib plus letrozole), may hinge on the specific CDK4/6 inhibitor. “Future studies are needed to identify the appropriate setting and sequence for chemotherapy in these patients,” they maintained.
Outcomes were similar for comparable regimens containing the three currently approved CDK4/6 inhibitors, but individual resistance mechanisms have yet to be elucidated, according to Dr. Nasrazadani and Dr. Brufsky. In addition, it is unclear how these agents may affect duration of response to subsequent therapies, as evidence of a broad overall survival benefit is lacking.
“With the ever-increasing range of targeted therapies gaining approval for metastatic breast cancer, the clinical and research community continues to move further away from a monotherapy approach,” they concluded. “Trials are currently in progress evaluating the role of inhibitors of phosphoinositide 3-kinase, mammalian target of rapamycin, and MEK, among others. How these agents will compare to previously frontline chemotherapy, and whether we will gain more success with the combinations of these targeted therapies in addition to CDK4/6 inhibitors remains to be seen.”
Dr. Nasrazadani is a fellow in the division of hematology/oncology at the University of Pittsburgh Medical Center–Magee-Women’s Hospital. Dr. Brufsky is associate chief of the division of hematology/oncology and codirector of the Comprehensive Breast Cancer Center at Magee-Women’s Hospital. Dr. Brufsky reported receiving personal fees from numerous pharmaceutical companies; Dr. Nasrazadani reported no conflicts of interest.
“This meta-analysis solidifies an increasingly accepted role for CDK4/6 inhibitors in the upfront treatment of postmenopausal women with hormone receptor–positive, HER2-negative metastatic breast cancer,” Azadeh Nasrazadani, PhD, MD, and Adam M. Brufsky, MD, PhD, wrote in an editorial published in Lancet Oncology. “These agents are starting to displace more toxic chemotherapy agents as frontline treatments for estrogen receptor–positive metastatic breast cancer in general practice because of, to some extent, their similar efficacy with substantially more favorable side-effect profiles.”
Nonetheless, chemotherapy still has a role in this population, typically in the later-line setting and in patients experiencing a visceral crisis, they noted. However, the better overall response rate seen with a chemotherapy regimen (paclitaxel plus bevacizumab), compared with a combination targeted and hormonal therapy regimen (palbociclib plus letrozole), may hinge on the specific CDK4/6 inhibitor. “Future studies are needed to identify the appropriate setting and sequence for chemotherapy in these patients,” they maintained.
Outcomes were similar for comparable regimens containing the three currently approved CDK4/6 inhibitors, but individual resistance mechanisms have yet to be elucidated, according to Dr. Nasrazadani and Dr. Brufsky. In addition, it is unclear how these agents may affect duration of response to subsequent therapies, as evidence of a broad overall survival benefit is lacking.
“With the ever-increasing range of targeted therapies gaining approval for metastatic breast cancer, the clinical and research community continues to move further away from a monotherapy approach,” they concluded. “Trials are currently in progress evaluating the role of inhibitors of phosphoinositide 3-kinase, mammalian target of rapamycin, and MEK, among others. How these agents will compare to previously frontline chemotherapy, and whether we will gain more success with the combinations of these targeted therapies in addition to CDK4/6 inhibitors remains to be seen.”
Dr. Nasrazadani is a fellow in the division of hematology/oncology at the University of Pittsburgh Medical Center–Magee-Women’s Hospital. Dr. Brufsky is associate chief of the division of hematology/oncology and codirector of the Comprehensive Breast Cancer Center at Magee-Women’s Hospital. Dr. Brufsky reported receiving personal fees from numerous pharmaceutical companies; Dr. Nasrazadani reported no conflicts of interest.
“This meta-analysis solidifies an increasingly accepted role for CDK4/6 inhibitors in the upfront treatment of postmenopausal women with hormone receptor–positive, HER2-negative metastatic breast cancer,” Azadeh Nasrazadani, PhD, MD, and Adam M. Brufsky, MD, PhD, wrote in an editorial published in Lancet Oncology. “These agents are starting to displace more toxic chemotherapy agents as frontline treatments for estrogen receptor–positive metastatic breast cancer in general practice because of, to some extent, their similar efficacy with substantially more favorable side-effect profiles.”
Nonetheless, chemotherapy still has a role in this population, typically in the later-line setting and in patients experiencing a visceral crisis, they noted. However, the better overall response rate seen with a chemotherapy regimen (paclitaxel plus bevacizumab), compared with a combination targeted and hormonal therapy regimen (palbociclib plus letrozole), may hinge on the specific CDK4/6 inhibitor. “Future studies are needed to identify the appropriate setting and sequence for chemotherapy in these patients,” they maintained.
Outcomes were similar for comparable regimens containing the three currently approved CDK4/6 inhibitors, but individual resistance mechanisms have yet to be elucidated, according to Dr. Nasrazadani and Dr. Brufsky. In addition, it is unclear how these agents may affect duration of response to subsequent therapies, as evidence of a broad overall survival benefit is lacking.
“With the ever-increasing range of targeted therapies gaining approval for metastatic breast cancer, the clinical and research community continues to move further away from a monotherapy approach,” they concluded. “Trials are currently in progress evaluating the role of inhibitors of phosphoinositide 3-kinase, mammalian target of rapamycin, and MEK, among others. How these agents will compare to previously frontline chemotherapy, and whether we will gain more success with the combinations of these targeted therapies in addition to CDK4/6 inhibitors remains to be seen.”
Dr. Nasrazadani is a fellow in the division of hematology/oncology at the University of Pittsburgh Medical Center–Magee-Women’s Hospital. Dr. Brufsky is associate chief of the division of hematology/oncology and codirector of the Comprehensive Breast Cancer Center at Magee-Women’s Hospital. Dr. Brufsky reported receiving personal fees from numerous pharmaceutical companies; Dr. Nasrazadani reported no conflicts of interest.
Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.
Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.
The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.
Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.
Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.
“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”
For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.
Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).
Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).
When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.
For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).
Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.
SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.
Combined hormone therapy and targeted therapy should be the first choice for most postmenopausal women with recently diagnosed hormone receptor–positive, HER2-negative metastatic breast cancer, new data suggest.
Although guidelines support use of hormone therapies with or without targeted therapies in this population, up-front chemotherapy is still commonly used even in the absence of a visceral crisis, noted lead investigator Mario Giuliano, MD, PhD, of the department of clinical medicine and surgery at the University of Naples (Italy) Federico II, and colleagues.
The investigators undertook a systematic review and network meta-analysis of 140 randomized, controlled trials among 50,029 postmenopausal patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated in the first- and/or second-line setting.
Study results, reported in Lancet Oncology, showed that relative to standard hormone therapy alone, the combination of hormone therapy with a targeted therapy – a CDK4/6 inhibitor, an mammalian target of rapamycin inhibitor, or an indicated phosphoinositide 3-kinase inhibitor – had significantly better efficacy, reducing the risk of progression-free survival events by more than half. In addition, no chemotherapy regimen, with or without targeted therapy, significantly outperformed the combination of hormone therapy with a CDK4/6 inhibitor.
Meanwhile, the hormone therapy–targeted therapy combinations had manageable toxicity, with the severity of adverse effects intermediate between that of hormone therapy alone and that of chemotherapy with or without targeted therapies.
“This study is, to our knowledge, the first to compare the efficacy and activity of all currently available chemotherapy and hormone therapy regimens, in combination with or without targeted therapies,” Dr. Giuliano and coinvestigators wrote. “[O]ur results corroborate the treatment algorithms recommended by the official oncology guidelines, supporting the use of new combinations of hormone therapies plus targeted therapies in the first-line or second-line setting in patients with hormone receptor-positive, HER2-negative metastatic breast cancer without visceral crisis.”
For the study, the investigators identified relevant phase 2 and phase 3 randomized, controlled trials published between 2000 and 2017, with the addition of several recently reported trials such as BOLERO-6 (JAMA Oncol. 2018;4:1367-74). Of the 140 trials ultimately included, 114 were used in the analysis of progression-free survival and time to progression, and 135 were used in the analysis of overall response.
Study results showed that when anastrozole (Arimidex) alone was the comparator, progression-free survival was significantly better with palbociclib (Ibrance) plus letrozole (Femara) (hazard ratio for events, 0.42); ribociclib (Kisqali) plus letrozole (HR, 0.43); abemaciclib (Verzenio) plus anastrozole or letrozole (HR, 0.42); palbociclib plus fulvestrant (Faslodex) (HR, 0.37); ribociclib plus fulvestrant (HR, 0.48); abemaciclib plus fulvestrant (HR, 0.44); everolimus (Afinitor) plus exemestane (Aromasin) (HR, 0.42); and, in patients with a PIK3CA mutation, the PI3K inhibitor alpelisib (Piqray) plus fulvestrant (HR, 0.39).
Several chemotherapy-based regimens, including anthracycline- and taxane-containing regimens, were also superior to anastrozole alone (hazard ratios, 0.41-0.47).
When palbociclib plus letrozole was the comparator, no chemotherapy or hormone therapy regimen yielded significantly better progression-free survival.
For the outcome of overall response, paclitaxel (Taxol) plus bevacizumab (Avastin) was the only clinically relevant regimen that significantly improved the likelihood of response relative to palbociclib plus letrozole (odds ratio, 8.95).
Dr. Giuliano reported that he receives honoraria from Amgen, AstraZeneca, Celgene, Eisai, Eli Lilly, Novartis, Pfizer,and Roche. The study did not receive any funding.
SOURCE: Giuliano M et al. Lancet Oncol. 2019 Sep 4. doi: 10.1016/S1470-2045(19)30420-6.
FROM LANCET ONCOLOGY