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Aromatase inhibitor effect on endothelial function may lead to CVD
SAN ANTONIO – Aromatase inhibitors, a mainstay of therapy in postmenopausal women with operable hormone receptor–positive breast cancers, are associated with reductions in endothelial function that could contribute to the development of cardiovascular disease, independent of the duration of therapy, investigators have found.
In a cross-sectional study examining endothelial function among postmenopausal women with locally advanced breast cancer on an aromatase inhibitor (AI), there were trends toward reduction in large and small artery elasticity and a significant decrement in vascular tone, compared with the vessels of healthy controls, reported Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis.
“Other studies have suggested that the cardiac risk from aromatase inhibitors is increased further in those with a previous diagnosis of cardiovascular disease. In this study we did not include this patient population, but I really think further work needs to be done in this area,” she said at the San Antonio Breast Cancer Symposium.
Her group’s findings suggest that prospective breast cancer trials need biomarkers to predict cardiovascular risk for patients who are on chronic AI therapy, she said.
CV incidence modest, deaths lows
The incidence rates of cardiovascular disease in clinical trials of adjuvant AI therapy have ranged from 3% to 17%, although the incidence of death from cardiovascular disease was relatively low in these trials, on the order of 1%-2%. Data on cardiovascular risk factors, however, were inconsistently collected across the various studies, Dr. Blaes noted.
“More recently, a lot of discussion has gone on about both the use of prolonged endocrine therapy using aromatase inhibitors – whether to consider 5 or 10 years – and in addition, as our population is aging, competing risks for mortality, whether that’s breast cancer or cardiovascular risk,” she said.
The investigators examined endothelial function in 36 postmenopausal women with locally advanced, operable breast cancer treated with curative intent with adjuvant AI therapy, and compared results with those of 25 healthy postmenopausal volunteers, five of whom were excluded from the final analysis due to prior use of exogenous estrogen.
About half of the patients had received chemotherapy, and two-thirds had received radiation therapy. The AIs used for most patients were anastrozole (Arimidex) and letrozole (Femara). Seven of the 36 cases had previously received tamoxifen.
The authors measured endothelial function using the EndoPAT (Itamar Medical) system that measures peripheral arterial tone (PAT) to identify reactive hyperemia. Endothelial dysfunction measured this way has been associated with an increased risk of cardiac adverse events independent of the Framingham Risk Score, Dr. Blaes said.
The participants underwent biomarker analysis and pulse wave analysis using a cardiovascular profiling system, and pulse contour analysis using the Endo-PAT2000 system. The investigators then compared biomarkers and functional test markers between cases and controls using T-tests and Wilcoxon Rank-Sum tests.
Biomarkers included inflammatory markers (high-sensitivity C-reactive protein, white blood cell count, interleukin 6), markers of hemostasis (fibrinogen, d-dimer, plasminogen-activator inhibitor-1, tissue-type plasminogen activator), and endothelial function markers (von Willebrand factor, circulating endothelial cells, soluble vascular cell adhesion molecule-1, and others).
They measured large-artery elasticity (LAE), small-artery elasticity (SAE), and the EndoPAT ratio, or reactive hyperemia index (RHI), the post-to-pre occlusion PAT signal ratio in the occluded side, normalized to the control side and further corrected for baseline vascular tone. An RHI score above 1.67 is considered normal, and a score of 1.67 or below is considered abnormal.
They found that both LAE and SAE trended toward significantly worse vascular tone in cases, compared with controls, but the differences were not statistically significant. The EndoPAT ratio, however, was significantly worse among cases, at 0.8, compared with 2.6 for controls, a difference that remained significant after controlling for systolic blood pressure (P less than .0001).
Hemostatic and endothelial biomarkers were significantly elevated in cases, compared with controls, but there were no significant differences in inflammatory markers.
When the investigators looked at the association between vascular function and cancer treatment characteristics, they found no differences in the use of chemotherapy, radiation, or left vs. right breast treated.
The use of anastrozole was associated with a significant reduction in LAE, compared with either letrozole or exemestane (P = .03). There was no association between duration of AI therapy and EndoPAT ratio.
Estradiol levels implicated
Not surprisingly, women on endocrine therapy in the study had significantly lower levels of estradiol than controls. Estradiol appears to be important for regulating healthy endothelial function, commented Patricia A. Ganz, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was the invited discussant.
“I think these are very provocative, hypothesis-generating findings, and I think they really fit what we expect the physiology should be in terms of endothelial function, even within this postmenopausal group of women where we’re looking at two discrete groups in terms of the estradiol level,” she said.
The study was funded by Building Interdisciplinary Research Careers in Women’s Health and a Masonic Scholar Award. Dr. Blaes and Dr. Ganz reported no relevant conflicts of interest.
SAN ANTONIO – Aromatase inhibitors, a mainstay of therapy in postmenopausal women with operable hormone receptor–positive breast cancers, are associated with reductions in endothelial function that could contribute to the development of cardiovascular disease, independent of the duration of therapy, investigators have found.
In a cross-sectional study examining endothelial function among postmenopausal women with locally advanced breast cancer on an aromatase inhibitor (AI), there were trends toward reduction in large and small artery elasticity and a significant decrement in vascular tone, compared with the vessels of healthy controls, reported Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis.
“Other studies have suggested that the cardiac risk from aromatase inhibitors is increased further in those with a previous diagnosis of cardiovascular disease. In this study we did not include this patient population, but I really think further work needs to be done in this area,” she said at the San Antonio Breast Cancer Symposium.
Her group’s findings suggest that prospective breast cancer trials need biomarkers to predict cardiovascular risk for patients who are on chronic AI therapy, she said.
CV incidence modest, deaths lows
The incidence rates of cardiovascular disease in clinical trials of adjuvant AI therapy have ranged from 3% to 17%, although the incidence of death from cardiovascular disease was relatively low in these trials, on the order of 1%-2%. Data on cardiovascular risk factors, however, were inconsistently collected across the various studies, Dr. Blaes noted.
“More recently, a lot of discussion has gone on about both the use of prolonged endocrine therapy using aromatase inhibitors – whether to consider 5 or 10 years – and in addition, as our population is aging, competing risks for mortality, whether that’s breast cancer or cardiovascular risk,” she said.
The investigators examined endothelial function in 36 postmenopausal women with locally advanced, operable breast cancer treated with curative intent with adjuvant AI therapy, and compared results with those of 25 healthy postmenopausal volunteers, five of whom were excluded from the final analysis due to prior use of exogenous estrogen.
About half of the patients had received chemotherapy, and two-thirds had received radiation therapy. The AIs used for most patients were anastrozole (Arimidex) and letrozole (Femara). Seven of the 36 cases had previously received tamoxifen.
The authors measured endothelial function using the EndoPAT (Itamar Medical) system that measures peripheral arterial tone (PAT) to identify reactive hyperemia. Endothelial dysfunction measured this way has been associated with an increased risk of cardiac adverse events independent of the Framingham Risk Score, Dr. Blaes said.
The participants underwent biomarker analysis and pulse wave analysis using a cardiovascular profiling system, and pulse contour analysis using the Endo-PAT2000 system. The investigators then compared biomarkers and functional test markers between cases and controls using T-tests and Wilcoxon Rank-Sum tests.
Biomarkers included inflammatory markers (high-sensitivity C-reactive protein, white blood cell count, interleukin 6), markers of hemostasis (fibrinogen, d-dimer, plasminogen-activator inhibitor-1, tissue-type plasminogen activator), and endothelial function markers (von Willebrand factor, circulating endothelial cells, soluble vascular cell adhesion molecule-1, and others).
They measured large-artery elasticity (LAE), small-artery elasticity (SAE), and the EndoPAT ratio, or reactive hyperemia index (RHI), the post-to-pre occlusion PAT signal ratio in the occluded side, normalized to the control side and further corrected for baseline vascular tone. An RHI score above 1.67 is considered normal, and a score of 1.67 or below is considered abnormal.
They found that both LAE and SAE trended toward significantly worse vascular tone in cases, compared with controls, but the differences were not statistically significant. The EndoPAT ratio, however, was significantly worse among cases, at 0.8, compared with 2.6 for controls, a difference that remained significant after controlling for systolic blood pressure (P less than .0001).
Hemostatic and endothelial biomarkers were significantly elevated in cases, compared with controls, but there were no significant differences in inflammatory markers.
When the investigators looked at the association between vascular function and cancer treatment characteristics, they found no differences in the use of chemotherapy, radiation, or left vs. right breast treated.
The use of anastrozole was associated with a significant reduction in LAE, compared with either letrozole or exemestane (P = .03). There was no association between duration of AI therapy and EndoPAT ratio.
Estradiol levels implicated
Not surprisingly, women on endocrine therapy in the study had significantly lower levels of estradiol than controls. Estradiol appears to be important for regulating healthy endothelial function, commented Patricia A. Ganz, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was the invited discussant.
“I think these are very provocative, hypothesis-generating findings, and I think they really fit what we expect the physiology should be in terms of endothelial function, even within this postmenopausal group of women where we’re looking at two discrete groups in terms of the estradiol level,” she said.
The study was funded by Building Interdisciplinary Research Careers in Women’s Health and a Masonic Scholar Award. Dr. Blaes and Dr. Ganz reported no relevant conflicts of interest.
SAN ANTONIO – Aromatase inhibitors, a mainstay of therapy in postmenopausal women with operable hormone receptor–positive breast cancers, are associated with reductions in endothelial function that could contribute to the development of cardiovascular disease, independent of the duration of therapy, investigators have found.
In a cross-sectional study examining endothelial function among postmenopausal women with locally advanced breast cancer on an aromatase inhibitor (AI), there were trends toward reduction in large and small artery elasticity and a significant decrement in vascular tone, compared with the vessels of healthy controls, reported Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis.
“Other studies have suggested that the cardiac risk from aromatase inhibitors is increased further in those with a previous diagnosis of cardiovascular disease. In this study we did not include this patient population, but I really think further work needs to be done in this area,” she said at the San Antonio Breast Cancer Symposium.
Her group’s findings suggest that prospective breast cancer trials need biomarkers to predict cardiovascular risk for patients who are on chronic AI therapy, she said.
CV incidence modest, deaths lows
The incidence rates of cardiovascular disease in clinical trials of adjuvant AI therapy have ranged from 3% to 17%, although the incidence of death from cardiovascular disease was relatively low in these trials, on the order of 1%-2%. Data on cardiovascular risk factors, however, were inconsistently collected across the various studies, Dr. Blaes noted.
“More recently, a lot of discussion has gone on about both the use of prolonged endocrine therapy using aromatase inhibitors – whether to consider 5 or 10 years – and in addition, as our population is aging, competing risks for mortality, whether that’s breast cancer or cardiovascular risk,” she said.
The investigators examined endothelial function in 36 postmenopausal women with locally advanced, operable breast cancer treated with curative intent with adjuvant AI therapy, and compared results with those of 25 healthy postmenopausal volunteers, five of whom were excluded from the final analysis due to prior use of exogenous estrogen.
About half of the patients had received chemotherapy, and two-thirds had received radiation therapy. The AIs used for most patients were anastrozole (Arimidex) and letrozole (Femara). Seven of the 36 cases had previously received tamoxifen.
The authors measured endothelial function using the EndoPAT (Itamar Medical) system that measures peripheral arterial tone (PAT) to identify reactive hyperemia. Endothelial dysfunction measured this way has been associated with an increased risk of cardiac adverse events independent of the Framingham Risk Score, Dr. Blaes said.
The participants underwent biomarker analysis and pulse wave analysis using a cardiovascular profiling system, and pulse contour analysis using the Endo-PAT2000 system. The investigators then compared biomarkers and functional test markers between cases and controls using T-tests and Wilcoxon Rank-Sum tests.
Biomarkers included inflammatory markers (high-sensitivity C-reactive protein, white blood cell count, interleukin 6), markers of hemostasis (fibrinogen, d-dimer, plasminogen-activator inhibitor-1, tissue-type plasminogen activator), and endothelial function markers (von Willebrand factor, circulating endothelial cells, soluble vascular cell adhesion molecule-1, and others).
They measured large-artery elasticity (LAE), small-artery elasticity (SAE), and the EndoPAT ratio, or reactive hyperemia index (RHI), the post-to-pre occlusion PAT signal ratio in the occluded side, normalized to the control side and further corrected for baseline vascular tone. An RHI score above 1.67 is considered normal, and a score of 1.67 or below is considered abnormal.
They found that both LAE and SAE trended toward significantly worse vascular tone in cases, compared with controls, but the differences were not statistically significant. The EndoPAT ratio, however, was significantly worse among cases, at 0.8, compared with 2.6 for controls, a difference that remained significant after controlling for systolic blood pressure (P less than .0001).
Hemostatic and endothelial biomarkers were significantly elevated in cases, compared with controls, but there were no significant differences in inflammatory markers.
When the investigators looked at the association between vascular function and cancer treatment characteristics, they found no differences in the use of chemotherapy, radiation, or left vs. right breast treated.
The use of anastrozole was associated with a significant reduction in LAE, compared with either letrozole or exemestane (P = .03). There was no association between duration of AI therapy and EndoPAT ratio.
Estradiol levels implicated
Not surprisingly, women on endocrine therapy in the study had significantly lower levels of estradiol than controls. Estradiol appears to be important for regulating healthy endothelial function, commented Patricia A. Ganz, MD, of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was the invited discussant.
“I think these are very provocative, hypothesis-generating findings, and I think they really fit what we expect the physiology should be in terms of endothelial function, even within this postmenopausal group of women where we’re looking at two discrete groups in terms of the estradiol level,” she said.
The study was funded by Building Interdisciplinary Research Careers in Women’s Health and a Masonic Scholar Award. Dr. Blaes and Dr. Ganz reported no relevant conflicts of interest.
AT SABCS 2016
Key clinical point: Aromatase inhibitors appear to have a decremental effect on vascular endothelial function, which could contribute to cardiovascular disease.
Major finding: Postmenopausal breast cancer survivors had significantly worse endothelial function than healthy postmenopausal controls, as measured by the EndoPAT ratio.
Data source: Case-control study with 36 postmenopausal breast cancer survivors on aromatase inhibitors and 25 healthy controls.
Disclosures: The study was funded by Building Interdisciplinary Research Careers in Women’s Health and a Masonic Scholar Award. Dr. Blaes and Dr. Ganz reported no relevant conflicts of interest.
VIDEO: No effect of BRCA status on overall outcomes in early-onset breast cancer
SAN ANTONIO – No difference in outcomes was seen among young BRCA gene mutation carriers and noncarriers with early-stage invasive breast cancer in a large cohort in the United Kingdom, but a subgroup analysis of those with triple-negative breast cancer showed a clear survival advantage among BRCA mutation carriers.
The findings of the POSH (Prospective Study of Outcomes in Sporadic Versus Hereditary Breast Cancer) trial have important implications for treatment decision making – particularly with respect to surgery – for younger women with breast cancer, according to Diana M. Eccles, MD, of the University of Southampton (England) and University Hospital Southampton Foundation Trust.
The overall finding of no difference in outcomes – including for the primary endpoint of overall survival and secondary endpoints of overall and distant disease-free survival – was true in both univariate and multivariable analysis of data for 2,759 women (14% with BRCA mutations), aged 40 years and younger, who were enrolled over an 8-year period, beginning in 2000, from 126 oncology centers across the United Kingdom, and who were followed for a median of 8.2 years, Dr. Eccles reported at the San Antonio Breast Cancer Symposium.
“We looked at BRCA1 and BRCA2 separately, and we still could see absolutely no difference in survival between BRCA1 and BRCA2, and we were well powered to show a difference,” she said, noting that 99% of these patients were diagnosed based on symptomatic presentation and did not know they were BRCA mutation carriers.
The findings were different among 511 patients with triple-negative breast cancer, however,
“Here we did see a clear difference in survival in favor of BRCA gene carriers – 11% at 10 years. And what was interesting was this clear time-varying hazard of relapse, with the maximum benefit of surviving in the BRCA gene carriers observed in the first few years with a hazard for relapse at 5 years equivalent between the two groups,” she said.
The primary treatment approach in these patients was no different than that in the group as a whole, Dr. Eccles noted, explaining that those with and without triple-negative disease had similar usage of breast conserving vs. unilateral surgery and similar usage of anthracycline-based chemotherapy regimens, with taxane added in a small proportion, which was “very typical for treatment regimens at the time.”
A proportion of women with BRCA gene mutations that were found in the clinical setting had opted to have bilateral mastectomy (15% vs. 3% of noncarriers) “closely following or during their primary treatment diagnosis,” and a separate analysis showed an intriguing survival benefit among those who did not have bilateral mastectomy; survival was 2% better among those women at 5 and 10 years, again with a time-varying hazard, Dr. Eccles said, noting, however, that the study was not powered to show a difference in this measure.
“It’s intriguing that bilateral mastectomy after diagnosis does not seem to improve survival in these young gene carriers. These are very small numbers so we have to be careful, but this is good news for patients. Many patients believe that being a BRCA gene carrier, or even just having a family history is going to give them an adverse prognosis, and that’s clearly not true – and it’s also important that patients who are facing the difficult, difficult decisions around chemotherapy and breast cancer treatment don’t feel compelled to make a decision about bilateral mastectomy within that time shortly after their diagnosis and can reasonably reserve judgment about the extent of surgery until a later date,” she said.
She discussed her findings further in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – No difference in outcomes was seen among young BRCA gene mutation carriers and noncarriers with early-stage invasive breast cancer in a large cohort in the United Kingdom, but a subgroup analysis of those with triple-negative breast cancer showed a clear survival advantage among BRCA mutation carriers.
The findings of the POSH (Prospective Study of Outcomes in Sporadic Versus Hereditary Breast Cancer) trial have important implications for treatment decision making – particularly with respect to surgery – for younger women with breast cancer, according to Diana M. Eccles, MD, of the University of Southampton (England) and University Hospital Southampton Foundation Trust.
The overall finding of no difference in outcomes – including for the primary endpoint of overall survival and secondary endpoints of overall and distant disease-free survival – was true in both univariate and multivariable analysis of data for 2,759 women (14% with BRCA mutations), aged 40 years and younger, who were enrolled over an 8-year period, beginning in 2000, from 126 oncology centers across the United Kingdom, and who were followed for a median of 8.2 years, Dr. Eccles reported at the San Antonio Breast Cancer Symposium.
“We looked at BRCA1 and BRCA2 separately, and we still could see absolutely no difference in survival between BRCA1 and BRCA2, and we were well powered to show a difference,” she said, noting that 99% of these patients were diagnosed based on symptomatic presentation and did not know they were BRCA mutation carriers.
The findings were different among 511 patients with triple-negative breast cancer, however,
“Here we did see a clear difference in survival in favor of BRCA gene carriers – 11% at 10 years. And what was interesting was this clear time-varying hazard of relapse, with the maximum benefit of surviving in the BRCA gene carriers observed in the first few years with a hazard for relapse at 5 years equivalent between the two groups,” she said.
The primary treatment approach in these patients was no different than that in the group as a whole, Dr. Eccles noted, explaining that those with and without triple-negative disease had similar usage of breast conserving vs. unilateral surgery and similar usage of anthracycline-based chemotherapy regimens, with taxane added in a small proportion, which was “very typical for treatment regimens at the time.”
A proportion of women with BRCA gene mutations that were found in the clinical setting had opted to have bilateral mastectomy (15% vs. 3% of noncarriers) “closely following or during their primary treatment diagnosis,” and a separate analysis showed an intriguing survival benefit among those who did not have bilateral mastectomy; survival was 2% better among those women at 5 and 10 years, again with a time-varying hazard, Dr. Eccles said, noting, however, that the study was not powered to show a difference in this measure.
“It’s intriguing that bilateral mastectomy after diagnosis does not seem to improve survival in these young gene carriers. These are very small numbers so we have to be careful, but this is good news for patients. Many patients believe that being a BRCA gene carrier, or even just having a family history is going to give them an adverse prognosis, and that’s clearly not true – and it’s also important that patients who are facing the difficult, difficult decisions around chemotherapy and breast cancer treatment don’t feel compelled to make a decision about bilateral mastectomy within that time shortly after their diagnosis and can reasonably reserve judgment about the extent of surgery until a later date,” she said.
She discussed her findings further in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – No difference in outcomes was seen among young BRCA gene mutation carriers and noncarriers with early-stage invasive breast cancer in a large cohort in the United Kingdom, but a subgroup analysis of those with triple-negative breast cancer showed a clear survival advantage among BRCA mutation carriers.
The findings of the POSH (Prospective Study of Outcomes in Sporadic Versus Hereditary Breast Cancer) trial have important implications for treatment decision making – particularly with respect to surgery – for younger women with breast cancer, according to Diana M. Eccles, MD, of the University of Southampton (England) and University Hospital Southampton Foundation Trust.
The overall finding of no difference in outcomes – including for the primary endpoint of overall survival and secondary endpoints of overall and distant disease-free survival – was true in both univariate and multivariable analysis of data for 2,759 women (14% with BRCA mutations), aged 40 years and younger, who were enrolled over an 8-year period, beginning in 2000, from 126 oncology centers across the United Kingdom, and who were followed for a median of 8.2 years, Dr. Eccles reported at the San Antonio Breast Cancer Symposium.
“We looked at BRCA1 and BRCA2 separately, and we still could see absolutely no difference in survival between BRCA1 and BRCA2, and we were well powered to show a difference,” she said, noting that 99% of these patients were diagnosed based on symptomatic presentation and did not know they were BRCA mutation carriers.
The findings were different among 511 patients with triple-negative breast cancer, however,
“Here we did see a clear difference in survival in favor of BRCA gene carriers – 11% at 10 years. And what was interesting was this clear time-varying hazard of relapse, with the maximum benefit of surviving in the BRCA gene carriers observed in the first few years with a hazard for relapse at 5 years equivalent between the two groups,” she said.
The primary treatment approach in these patients was no different than that in the group as a whole, Dr. Eccles noted, explaining that those with and without triple-negative disease had similar usage of breast conserving vs. unilateral surgery and similar usage of anthracycline-based chemotherapy regimens, with taxane added in a small proportion, which was “very typical for treatment regimens at the time.”
A proportion of women with BRCA gene mutations that were found in the clinical setting had opted to have bilateral mastectomy (15% vs. 3% of noncarriers) “closely following or during their primary treatment diagnosis,” and a separate analysis showed an intriguing survival benefit among those who did not have bilateral mastectomy; survival was 2% better among those women at 5 and 10 years, again with a time-varying hazard, Dr. Eccles said, noting, however, that the study was not powered to show a difference in this measure.
“It’s intriguing that bilateral mastectomy after diagnosis does not seem to improve survival in these young gene carriers. These are very small numbers so we have to be careful, but this is good news for patients. Many patients believe that being a BRCA gene carrier, or even just having a family history is going to give them an adverse prognosis, and that’s clearly not true – and it’s also important that patients who are facing the difficult, difficult decisions around chemotherapy and breast cancer treatment don’t feel compelled to make a decision about bilateral mastectomy within that time shortly after their diagnosis and can reasonably reserve judgment about the extent of surgery until a later date,” she said.
She discussed her findings further in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2016
Key clinical point:
Major finding: A significant 11% improvement in overall survival was seen among BRCA mutation carriers vs. noncarriers with triple-negative breast cancer.
Data source: The prospective POSH trial included 2,759 women with early-stage invasive breast cancer.
Disclosures: Dr. Eccles has been a consultant for AstraZeneca.
No boost in pCR from neoadjuvant estrogen deprivation
SAN ANTONIO – Although adding concurrent estrogen deprivation to a standard combination chemotherapy regimen for women with breast cancers positive for the estrogen receptors (ER+) and the human epidermal growth factor receptor–2 (HER2+) did not add to the already considerable toxicity, it also did not seem to add much benefit, according to an investigator in the NSABP B-52 trial.
Among 311 women with ER+/HER2+ tumors randomized to neoadjuvant therapy with docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta) with or without estrogen deprivation therapy, there was no statistically significant difference in the primary endpoint of pathologic complete response (pCR) rates, reported Mothaffar F. Rimawi, MD, of the breast center at Baylor College of Medicine in Houston.
“I think the most important lesson from B-52 is that when we hit the tumors with everything we’ve got, this is what we have. We need to start thinking about whether we can, essentially, start dialing down these treatments. Can we omit one of the chemotherapy agents, if not both, and see what happens,” Dr. Rimawi said in an interview.
Endocrine/chemo interplay?
The rationale for the trial was based on several previous findings, including the propensity for ER+/HER2+ tumors to be less responsive to dual anti-HER2 therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta).
There is also evidence to suggest that the estrogen receptor may act as a pathway of resistance to anti-HER2 therapy, and evidence from older trials suggested that chemotherapy and endocrine therapy may have antagonistic effects, he said.
The investigators hypothesized that concurrent inhibition of ER and HER2 tumors with neoadjuvant chemotherapy consisting of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) would not be antagonistic, and could overcome resistance to treatment as shown by improvements in pathologic complete response rates.
The investigators enrolled women with HER+ and ER+ and/or progresterone receptor–positive (PR+) invasive breast cancer diagnosed by core needle biopsy, stratified them by premenopausal or postmenopausal status, and then randomized them to receive chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab every 21 days for six cycles, with or without estrogen deprivation therapy. Postmenopausal women received an aromatase inhibitor, and premenopausal women received an aromatase inhibitor plus ovarian suppression with goserelin and a lutenizing hormone–releasing hormone agonist.
For the primary endpoint, overall rates of pCR in the breast and nodes were 41% among 154 patients treated with TCHP chemotherapy alone, vs. 46% for 157 women treated with TCHP and estrogen deprivation, a difference that was not statistically significant. The results were similar in an analysis stratified by menopausal status: 44% vs. 46%, respectively, in premenopausal women, and 38% vs. 45% in postmenopausal women. Neither comparison was statistically significant.
In addition, no overall or stratified differences were seen in terms of pCR in the breast alone, and no differences were seen in clinical complete response rates, at 68.1% vs. 73.9%, respectively.
Nearly 100% of patients in the TCHP chemotherapy alone arm had diarrhea, ranging from 42% with grade 1, to 34% with grade 2, to 23% with grade 3, to less than 1% with grade 4. The distribution of diarrhea severity was virtually identical among patients treated with TCHP plus estrogen deprivation, all of whom experienced some grade. Other common gastrointestinal side effects in each study arm included nausea, vomiting, and dehydration, occurring in nearly all patients with equal distribution of severity between the two arms.
Hematologic toxicities included anemia, hypokalemia, and febrile neutropenia, again distributed evenly in severity between the trial arms.
Alternative endpoint?
Dr. Rimawi said the pCR endpoint commonly used in clinical trials may not be ideal for studying therapy in this population, because it generally correlates with outcomes among women when tumors are ER negative,“but when they are ER positive, the absence of a pathologic complete response is not necessarily a bad thing.”
He said that residual cancer burden, or RCB, appears to be a better marker for prognosis than pCR in patients with ER+/HER2+ tumors.
“In this population we need a different metric, a metric that is not path CR,” agreed Carlos Arteaga, MD, professor of cancer biology and medicine, and coleader of the breast cancer research program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
“We need other metrics that are more objective and more correlated with long-term outcomes. Path CR is not,” said Dr. Arteaga, who moderated a briefing where NSABP B-52 data were discussed prior to their presentation in the general session.
Regarding the lack of statistical significance, Dr. Rimawi said it is possible that the effects of chemotherapy may have blunted the responses that might otherwise have been seen with the addition of estrogen deprivation.
“We believe that if we de-escalate treatment, we could see a higher response to the estrogen receptor inhibitor,” he said.
NSABP B-52 was supported by the National Cancer Institute and Genentech. Dr. Rimawi reported contracted research from Genentech and GlaxoSmithKline. Dr. Arteaga reported no disclosures relevant to the trial.
SAN ANTONIO – Although adding concurrent estrogen deprivation to a standard combination chemotherapy regimen for women with breast cancers positive for the estrogen receptors (ER+) and the human epidermal growth factor receptor–2 (HER2+) did not add to the already considerable toxicity, it also did not seem to add much benefit, according to an investigator in the NSABP B-52 trial.
Among 311 women with ER+/HER2+ tumors randomized to neoadjuvant therapy with docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta) with or without estrogen deprivation therapy, there was no statistically significant difference in the primary endpoint of pathologic complete response (pCR) rates, reported Mothaffar F. Rimawi, MD, of the breast center at Baylor College of Medicine in Houston.
“I think the most important lesson from B-52 is that when we hit the tumors with everything we’ve got, this is what we have. We need to start thinking about whether we can, essentially, start dialing down these treatments. Can we omit one of the chemotherapy agents, if not both, and see what happens,” Dr. Rimawi said in an interview.
Endocrine/chemo interplay?
The rationale for the trial was based on several previous findings, including the propensity for ER+/HER2+ tumors to be less responsive to dual anti-HER2 therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta).
There is also evidence to suggest that the estrogen receptor may act as a pathway of resistance to anti-HER2 therapy, and evidence from older trials suggested that chemotherapy and endocrine therapy may have antagonistic effects, he said.
The investigators hypothesized that concurrent inhibition of ER and HER2 tumors with neoadjuvant chemotherapy consisting of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) would not be antagonistic, and could overcome resistance to treatment as shown by improvements in pathologic complete response rates.
The investigators enrolled women with HER+ and ER+ and/or progresterone receptor–positive (PR+) invasive breast cancer diagnosed by core needle biopsy, stratified them by premenopausal or postmenopausal status, and then randomized them to receive chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab every 21 days for six cycles, with or without estrogen deprivation therapy. Postmenopausal women received an aromatase inhibitor, and premenopausal women received an aromatase inhibitor plus ovarian suppression with goserelin and a lutenizing hormone–releasing hormone agonist.
For the primary endpoint, overall rates of pCR in the breast and nodes were 41% among 154 patients treated with TCHP chemotherapy alone, vs. 46% for 157 women treated with TCHP and estrogen deprivation, a difference that was not statistically significant. The results were similar in an analysis stratified by menopausal status: 44% vs. 46%, respectively, in premenopausal women, and 38% vs. 45% in postmenopausal women. Neither comparison was statistically significant.
In addition, no overall or stratified differences were seen in terms of pCR in the breast alone, and no differences were seen in clinical complete response rates, at 68.1% vs. 73.9%, respectively.
Nearly 100% of patients in the TCHP chemotherapy alone arm had diarrhea, ranging from 42% with grade 1, to 34% with grade 2, to 23% with grade 3, to less than 1% with grade 4. The distribution of diarrhea severity was virtually identical among patients treated with TCHP plus estrogen deprivation, all of whom experienced some grade. Other common gastrointestinal side effects in each study arm included nausea, vomiting, and dehydration, occurring in nearly all patients with equal distribution of severity between the two arms.
Hematologic toxicities included anemia, hypokalemia, and febrile neutropenia, again distributed evenly in severity between the trial arms.
Alternative endpoint?
Dr. Rimawi said the pCR endpoint commonly used in clinical trials may not be ideal for studying therapy in this population, because it generally correlates with outcomes among women when tumors are ER negative,“but when they are ER positive, the absence of a pathologic complete response is not necessarily a bad thing.”
He said that residual cancer burden, or RCB, appears to be a better marker for prognosis than pCR in patients with ER+/HER2+ tumors.
“In this population we need a different metric, a metric that is not path CR,” agreed Carlos Arteaga, MD, professor of cancer biology and medicine, and coleader of the breast cancer research program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
“We need other metrics that are more objective and more correlated with long-term outcomes. Path CR is not,” said Dr. Arteaga, who moderated a briefing where NSABP B-52 data were discussed prior to their presentation in the general session.
Regarding the lack of statistical significance, Dr. Rimawi said it is possible that the effects of chemotherapy may have blunted the responses that might otherwise have been seen with the addition of estrogen deprivation.
“We believe that if we de-escalate treatment, we could see a higher response to the estrogen receptor inhibitor,” he said.
NSABP B-52 was supported by the National Cancer Institute and Genentech. Dr. Rimawi reported contracted research from Genentech and GlaxoSmithKline. Dr. Arteaga reported no disclosures relevant to the trial.
SAN ANTONIO – Although adding concurrent estrogen deprivation to a standard combination chemotherapy regimen for women with breast cancers positive for the estrogen receptors (ER+) and the human epidermal growth factor receptor–2 (HER2+) did not add to the already considerable toxicity, it also did not seem to add much benefit, according to an investigator in the NSABP B-52 trial.
Among 311 women with ER+/HER2+ tumors randomized to neoadjuvant therapy with docetaxel, carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta) with or without estrogen deprivation therapy, there was no statistically significant difference in the primary endpoint of pathologic complete response (pCR) rates, reported Mothaffar F. Rimawi, MD, of the breast center at Baylor College of Medicine in Houston.
“I think the most important lesson from B-52 is that when we hit the tumors with everything we’ve got, this is what we have. We need to start thinking about whether we can, essentially, start dialing down these treatments. Can we omit one of the chemotherapy agents, if not both, and see what happens,” Dr. Rimawi said in an interview.
Endocrine/chemo interplay?
The rationale for the trial was based on several previous findings, including the propensity for ER+/HER2+ tumors to be less responsive to dual anti-HER2 therapy with trastuzumab (Herceptin) and pertuzumab (Perjeta).
There is also evidence to suggest that the estrogen receptor may act as a pathway of resistance to anti-HER2 therapy, and evidence from older trials suggested that chemotherapy and endocrine therapy may have antagonistic effects, he said.
The investigators hypothesized that concurrent inhibition of ER and HER2 tumors with neoadjuvant chemotherapy consisting of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) would not be antagonistic, and could overcome resistance to treatment as shown by improvements in pathologic complete response rates.
The investigators enrolled women with HER+ and ER+ and/or progresterone receptor–positive (PR+) invasive breast cancer diagnosed by core needle biopsy, stratified them by premenopausal or postmenopausal status, and then randomized them to receive chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab every 21 days for six cycles, with or without estrogen deprivation therapy. Postmenopausal women received an aromatase inhibitor, and premenopausal women received an aromatase inhibitor plus ovarian suppression with goserelin and a lutenizing hormone–releasing hormone agonist.
For the primary endpoint, overall rates of pCR in the breast and nodes were 41% among 154 patients treated with TCHP chemotherapy alone, vs. 46% for 157 women treated with TCHP and estrogen deprivation, a difference that was not statistically significant. The results were similar in an analysis stratified by menopausal status: 44% vs. 46%, respectively, in premenopausal women, and 38% vs. 45% in postmenopausal women. Neither comparison was statistically significant.
In addition, no overall or stratified differences were seen in terms of pCR in the breast alone, and no differences were seen in clinical complete response rates, at 68.1% vs. 73.9%, respectively.
Nearly 100% of patients in the TCHP chemotherapy alone arm had diarrhea, ranging from 42% with grade 1, to 34% with grade 2, to 23% with grade 3, to less than 1% with grade 4. The distribution of diarrhea severity was virtually identical among patients treated with TCHP plus estrogen deprivation, all of whom experienced some grade. Other common gastrointestinal side effects in each study arm included nausea, vomiting, and dehydration, occurring in nearly all patients with equal distribution of severity between the two arms.
Hematologic toxicities included anemia, hypokalemia, and febrile neutropenia, again distributed evenly in severity between the trial arms.
Alternative endpoint?
Dr. Rimawi said the pCR endpoint commonly used in clinical trials may not be ideal for studying therapy in this population, because it generally correlates with outcomes among women when tumors are ER negative,“but when they are ER positive, the absence of a pathologic complete response is not necessarily a bad thing.”
He said that residual cancer burden, or RCB, appears to be a better marker for prognosis than pCR in patients with ER+/HER2+ tumors.
“In this population we need a different metric, a metric that is not path CR,” agreed Carlos Arteaga, MD, professor of cancer biology and medicine, and coleader of the breast cancer research program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
“We need other metrics that are more objective and more correlated with long-term outcomes. Path CR is not,” said Dr. Arteaga, who moderated a briefing where NSABP B-52 data were discussed prior to their presentation in the general session.
Regarding the lack of statistical significance, Dr. Rimawi said it is possible that the effects of chemotherapy may have blunted the responses that might otherwise have been seen with the addition of estrogen deprivation.
“We believe that if we de-escalate treatment, we could see a higher response to the estrogen receptor inhibitor,” he said.
NSABP B-52 was supported by the National Cancer Institute and Genentech. Dr. Rimawi reported contracted research from Genentech and GlaxoSmithKline. Dr. Arteaga reported no disclosures relevant to the trial.
AT SABCS 2016
Key clinical point: Estrogen deprivation added to chemotherapy and dual HER2 inhibition did not improve pathologic complete responses, compared with chemotherapy alone.
Major finding: The pathologic complete response rate for women with ER-positive/HER2-positive tumors was 41%, without estrogen deprivation, vs. 46% with estrogen deprivation (a nonsignficant difference).
Data source: A randomized phase III trial of neoadjuvant therapy in 311 women with ER+/HER2+ breast cancers.
Disclosures: NSABP-B52 was supported by the National Cancer Institute and Genentech. Dr. Rimawi reported contracted research from Genentech and GlaxoSmithKline. Dr. Arteaga reported no disclosures relevant to the trial.
VIDEO: No improvement in pCR with dual ER and HER2 inhibition
SAN ANTONIO – Breast cancers that are positive for the estrogen receptor (ER) and human epidermal growth factor receptor–2 (HER2) are less likely than ER-negative/HER2-positive tumors to respond to dual anti-HER2 therapy, suggesting that the estrogen receptor may act as a pathway of resistance to anti-HER2 treatment.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-52 trial was designed to test the hypothesis that concurrent inhibition of both ER and HER2 added to chemotherapy with a platinum compound and a taxane will overcome resistance to treatment and improve pathologic complete response (pCR) rates in patients with ER-positive/HER2-positive breast cancer.
In a video interview at the San Antonio Breast Cancer Symposium, Mothaffar F. Rimawi, MD, discusses the trial results, which failed to show a significant difference in pCR rates between women who received chemotherapy with estrogen deprivation or chemotherapy alone. However, the trial still provided important information about the interplay between hormonal and HER2 receptors, and may inform future clinical trials examining reduction in tumor burden as a prognostic measure, says Dr. Rimawi from the Breast Center at Baylor College of Medicine, Houston.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Breast cancers that are positive for the estrogen receptor (ER) and human epidermal growth factor receptor–2 (HER2) are less likely than ER-negative/HER2-positive tumors to respond to dual anti-HER2 therapy, suggesting that the estrogen receptor may act as a pathway of resistance to anti-HER2 treatment.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-52 trial was designed to test the hypothesis that concurrent inhibition of both ER and HER2 added to chemotherapy with a platinum compound and a taxane will overcome resistance to treatment and improve pathologic complete response (pCR) rates in patients with ER-positive/HER2-positive breast cancer.
In a video interview at the San Antonio Breast Cancer Symposium, Mothaffar F. Rimawi, MD, discusses the trial results, which failed to show a significant difference in pCR rates between women who received chemotherapy with estrogen deprivation or chemotherapy alone. However, the trial still provided important information about the interplay between hormonal and HER2 receptors, and may inform future clinical trials examining reduction in tumor burden as a prognostic measure, says Dr. Rimawi from the Breast Center at Baylor College of Medicine, Houston.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Breast cancers that are positive for the estrogen receptor (ER) and human epidermal growth factor receptor–2 (HER2) are less likely than ER-negative/HER2-positive tumors to respond to dual anti-HER2 therapy, suggesting that the estrogen receptor may act as a pathway of resistance to anti-HER2 treatment.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-52 trial was designed to test the hypothesis that concurrent inhibition of both ER and HER2 added to chemotherapy with a platinum compound and a taxane will overcome resistance to treatment and improve pathologic complete response (pCR) rates in patients with ER-positive/HER2-positive breast cancer.
In a video interview at the San Antonio Breast Cancer Symposium, Mothaffar F. Rimawi, MD, discusses the trial results, which failed to show a significant difference in pCR rates between women who received chemotherapy with estrogen deprivation or chemotherapy alone. However, the trial still provided important information about the interplay between hormonal and HER2 receptors, and may inform future clinical trials examining reduction in tumor burden as a prognostic measure, says Dr. Rimawi from the Breast Center at Baylor College of Medicine, Houston.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2016
Optimal duration of extended AI therapy? Flip a coin
SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.
For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.
DATA data
In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.
They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.
“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.
Less than ideal
In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.
They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.
“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.
Give what to whom for how long?
Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.
“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.
“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.
What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”
The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.
For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.
“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.
Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.
Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.
Biomarkers needed
“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.
There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.
Dr. Bardia was not involved in the studies.
NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.
SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.
For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.
DATA data
In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.
They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.
“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.
Less than ideal
In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.
They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.
“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.
Give what to whom for how long?
Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.
“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.
“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.
What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”
The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.
For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.
“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.
Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.
Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.
Biomarkers needed
“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.
There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.
Dr. Bardia was not involved in the studies.
NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.
SAN ANTONIO – When does adjuvant therapy with an aromatase inhibitor become too much of a good thing? Or to put it another way, what’s the optimal duration of extended aromatase inhibitor therapy? That’s the question that three clinical trials have tried – but largely failed – to answer.
For example, the randomized, double-blinded NSABP B-42 trial, comparing extended therapy with letrozole (Femara) in postmenopausal women with hormone receptor–positive (HR+) breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) showed no difference in disease-free survival (DFS) after 7 years of follow-up between women treated with extended letrozole or placebo.
DATA data
In the DATA study, also presented here, investigators from the Netherlands compared 6 years of anastrozole (Arimidex) to 3 years of anastrozole following 2 or 3 years of adjuvant tamoxifen for postmenopausal women with estrogen receptor–positive (ER+), and/or progesterone receptor–positive (PR+) breast cancer.
They found that “adapted” DFS (DFS starting 3 years after randomization) and adapted overall survival (OS) were similar between the two groups.
“The findings of the DATA study do not support extended adjuvant AI use after 5 years of sequential endocrine therapy for all postmenopausal hormone receptor–positive breast cancer patients,” said Vivianne Tjan-Heijnen, MD, of Maastricht University Medical Center in the Netherlands.
Less than ideal
In the optimistically named IDEAL trial, a separate team of investigators, also from the Netherlands, looked at the relative merits of continuing adjuvant therapy with letrozole for 2.5 or 5 years following 5 years of adjuvant therapy with tamoxifen, an AI, or a combination in postmenopausal women with HR+ breast cancer.
They found no differences in either DFS or OS between patients treated for 5 years or those treated for only half that long.
“We conclude that there is no benefit of extending AI-based therapy longer than two-and-a-half years,” said Erik Blok, MD, of Leiden University Medical Center in the Netherlands.
Give what to whom for how long?
Results of the trials raise more questions than they answer, said Michael Gnant, MD, of the Medical University of Vienna, the invited discussant.
“Essentially, these three trials did not reach the necessary statistical significance levels to demonstrate a clear benefit for the respective AI extension,” he said.
“Can other agents we use in luminal breast cancer help? Frankly, I don’t think so. Based on their tolerability profile, and in part also on financial toxicity, I don’t think that the promising agents we explore in many situations for the treatment of hormone receptor–positive breast cancer will realistically be used in the extended adjuvant setting,” he said.
What’s needed, he said, are new strategies for targeting the chronic part of luminal breast cancer recurrence risk. Using endocrine therapies in this setting will likely be ineffective. Instead, agents that could directly target dormant cancer stem cells would “eliminate the source of late metastases for good.”
The best evidence to date clearly points to individualized treatment plans for patients, Dr. Gnant said.
For example, for a patient who has had 2-5 years of tamoxifen, an AI for 2.5-5 additional years can help to prevent recurrences, provided that the patient has risk factors for recurrence and excellent bone health.
“Based on the trial results, it is more complex for a patient who comes off initial or sequential AI. There are factors favoring the extension of AI treatment, and other factors to speak against such extension. I suggest to start with patient features at this time,” he said.
Currently, the main factor driving the choice of extended AI therapy will be how well the patient has tolerated AIs in the first years of therapy and whether she is at increased risk for fractures, suggesting younger age as a factor favoring extended AI use.
Patients with higher clinicopathologic risk factors such as node positivity or more luminal type tumors, as well as higher risk according to genomic studies, might also benefit from extended AI therapy, he said.
Biomarkers needed
“What the data from these and other trials tell us is that endocrine therapy is not for everyone. We need biomarkers that can tell us who should be getting extended endocrine therapy, be it 10 years or even a longer duration of time, versus a subgroup that might do very well with 5 five years of AI,” Aditya Bardia, MBBS, MPH, of the breast cancer division at Massachusetts General Hospital Cancer Center in Boston, said in an interview.
There are several such biomarkers under investigation, but they need validation and testing in large scale clinical trials before they find their way into day-to-practice, he said.
Dr. Bardia was not involved in the studies.
NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.
AT SABCS 2016
Key clinical point: The optimal duration of aromatase inhibitor (AI) therapy following 5 years of endocrine therapy in postmenopausal women is still unknown.
Major finding: There were no significant differences in disease-free or overall survival in three studies investigating extended AI therapy.
Data source: Randomized phase II NSABP B-42 with 3,996 patients; randomized phase III DATA study with 1,912 patients; randomized phase III IDEAL trial with 1,824 patients.
Disclosures: NSABP B-42 was sponsored by PrECOG with financial support from Novartis. Dr. Mamounas reported having no conflicts of interest. The DATA trial was sponsored by the Dutch Breast Cancer Research Group and Novartis. Dr. Tjan-Heijnen reported nothing to disclose. IDEAL was supported by the Dutch Breast Cancer Research Group and Novartis. Dr. Blok reported nothing to disclose.
Next-generation sequencing highlights evolution of ER+ breast cancer
SAN ANTONIO – The “genomic landscape” of resistant estrogen receptor–positive (ER+) metastatic breast cancer differs significantly from that of ER+ primary breast cancer, according to findings from a study involving whole-exome sequencing and transcriptome sequencing of such cancers.
Multiple genes were recurrently altered in ER+ metastatic breast cancers at a rate significantly higher than in ER+ primary breast cancers (with 3- to 33-fold enrichment in metastatic vs. primary samples), Ofir Cohen, PhD, explained at the San Antonio Breast Cancer Symposium.
This finding, which suggests that recurrent alterations in genes in ER+ metastatic breast cancers are often acquired after treatment and thus may play a role in resistance to ER-directed therapies and/or metastasis, highlights the value of genomic profiling of metastatic biopsies and has implications for drug development, said Dr. Cohen of the Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard in Cambridge.
Although the genomic and molecular landscape of ER+ primary breast cancer is better understood, that of ER+ metastatic breast cancer is underexplored, he noted.
Thus, he and his colleagues performed whole-exome sequencing on 149 metastatic tumor biopsies from patients with ER+ metastatic tumors and resistance to at least one ER-directed therapy and compared the results with those from 44 matched primary samples from the same patient. They also performed transcriptome sequencing (RNA-seq) of 128 metastatic biopsies.
A key observation from the study is that ESR1 genes were mutated in 24% of the cohort, and the mutations were acquired in 14 of the 15 samples with matched primary samples.
“This emphasized the important role that these mutations may play, specifically in the metastatic and drug-resistant settings,” Dr. Cohen said.
Similarly, ERBB2 mutations occurred in 7% of samples, and seemed to be acquired in five of six metastatic samples with matched primary samples, he said.
“For both of these genes, other than being acquired and suggestive of importance, they also have clear clinical implications, as finding those mutations may guide treatment choices for those patients,” he said.
Another example involves RB1 mutations, which were found in 5% of samples, and which appeared to be acquired in three of five of those with matched primaries. More frequent alterations were also found in PIK3CA, PTEN, and AKTI genes, among others, in metastatic vs. primary cancers.
The observation that these tumors evolve and have different mutations in the primary and metastatic settings may be important, because this suggests that knowledge of the alterations and mutations in the primary setting is insufficient to guide treatment in the metastatic setting.
“So the take-home message here is that tumors do evolve, and that the metastatic setting is different than the primary setting,” Dr. Cohen said.
Sequencing both the exome and the transcriptome may “give us a handle to assess that,” he said.
“Our goal is really to understand evolved resistance. That is, to try and understand the mechanisms that drive the evolution of resistance in ER+ metastatic breast cancer, and, once we understand that, [to determine] how we can translate that knowledge in the clinic,” he said, noting that resistance also may develop through other nongenomic mechanisms, such as epigenetic and regulatory mechanisms.
“As long as those mechanisms leave a footprint on the transcriptome … sequencing the transcriptome together with the exome may yield relevant insights into resistance states that do not derive specifically from exome mutations,” he added.
The findings are important because, despite tremendous advances in the treatment of ER+ metastatic breast cancer, therapeutic resistance remains a common problem, and improved understanding of the underlying resistance mechanisms is critical for enabling durable control of this disease, Dr. Cohen said, explaining that resistant tumors remain the most common cause of breast cancer death and that there is an urgent need to develop new therapeutic strategies for patients who no longer respond to existing therapies.
In a written statement, senior investigator Nikhil Wagle, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston, said that the ultimate goal of the project is “to integrate the functional and clinical findings into a unified ‘Resistance Atlas’ for ER+ metastatic breast cancer, which should help inform treatment decisions for individual patients as well as propel the development of new combination treatment strategies for ER-positive metastatic breast cancer.”
This study was funded by the National Cancer Institute, the National Human Genome Research Institute, the Department of Defense Breast Cancer Research Program, Susan G. Komen, the V Foundation, the Breast Cancer Alliance, the AACR-Landon Foundation, the Friends of Dana-Farber Cancer Institute, and the Breast Cancer Research Foundation. Dr. Cohen reported having no conflicts of interest. Dr. Wagle is an equity holder in Foundation Medicine, a consultant to Novartis, and a recipient of sponsored research support from Novartis, Genentech, and Merck.
SAN ANTONIO – The “genomic landscape” of resistant estrogen receptor–positive (ER+) metastatic breast cancer differs significantly from that of ER+ primary breast cancer, according to findings from a study involving whole-exome sequencing and transcriptome sequencing of such cancers.
Multiple genes were recurrently altered in ER+ metastatic breast cancers at a rate significantly higher than in ER+ primary breast cancers (with 3- to 33-fold enrichment in metastatic vs. primary samples), Ofir Cohen, PhD, explained at the San Antonio Breast Cancer Symposium.
This finding, which suggests that recurrent alterations in genes in ER+ metastatic breast cancers are often acquired after treatment and thus may play a role in resistance to ER-directed therapies and/or metastasis, highlights the value of genomic profiling of metastatic biopsies and has implications for drug development, said Dr. Cohen of the Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard in Cambridge.
Although the genomic and molecular landscape of ER+ primary breast cancer is better understood, that of ER+ metastatic breast cancer is underexplored, he noted.
Thus, he and his colleagues performed whole-exome sequencing on 149 metastatic tumor biopsies from patients with ER+ metastatic tumors and resistance to at least one ER-directed therapy and compared the results with those from 44 matched primary samples from the same patient. They also performed transcriptome sequencing (RNA-seq) of 128 metastatic biopsies.
A key observation from the study is that ESR1 genes were mutated in 24% of the cohort, and the mutations were acquired in 14 of the 15 samples with matched primary samples.
“This emphasized the important role that these mutations may play, specifically in the metastatic and drug-resistant settings,” Dr. Cohen said.
Similarly, ERBB2 mutations occurred in 7% of samples, and seemed to be acquired in five of six metastatic samples with matched primary samples, he said.
“For both of these genes, other than being acquired and suggestive of importance, they also have clear clinical implications, as finding those mutations may guide treatment choices for those patients,” he said.
Another example involves RB1 mutations, which were found in 5% of samples, and which appeared to be acquired in three of five of those with matched primaries. More frequent alterations were also found in PIK3CA, PTEN, and AKTI genes, among others, in metastatic vs. primary cancers.
The observation that these tumors evolve and have different mutations in the primary and metastatic settings may be important, because this suggests that knowledge of the alterations and mutations in the primary setting is insufficient to guide treatment in the metastatic setting.
“So the take-home message here is that tumors do evolve, and that the metastatic setting is different than the primary setting,” Dr. Cohen said.
Sequencing both the exome and the transcriptome may “give us a handle to assess that,” he said.
“Our goal is really to understand evolved resistance. That is, to try and understand the mechanisms that drive the evolution of resistance in ER+ metastatic breast cancer, and, once we understand that, [to determine] how we can translate that knowledge in the clinic,” he said, noting that resistance also may develop through other nongenomic mechanisms, such as epigenetic and regulatory mechanisms.
“As long as those mechanisms leave a footprint on the transcriptome … sequencing the transcriptome together with the exome may yield relevant insights into resistance states that do not derive specifically from exome mutations,” he added.
The findings are important because, despite tremendous advances in the treatment of ER+ metastatic breast cancer, therapeutic resistance remains a common problem, and improved understanding of the underlying resistance mechanisms is critical for enabling durable control of this disease, Dr. Cohen said, explaining that resistant tumors remain the most common cause of breast cancer death and that there is an urgent need to develop new therapeutic strategies for patients who no longer respond to existing therapies.
In a written statement, senior investigator Nikhil Wagle, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston, said that the ultimate goal of the project is “to integrate the functional and clinical findings into a unified ‘Resistance Atlas’ for ER+ metastatic breast cancer, which should help inform treatment decisions for individual patients as well as propel the development of new combination treatment strategies for ER-positive metastatic breast cancer.”
This study was funded by the National Cancer Institute, the National Human Genome Research Institute, the Department of Defense Breast Cancer Research Program, Susan G. Komen, the V Foundation, the Breast Cancer Alliance, the AACR-Landon Foundation, the Friends of Dana-Farber Cancer Institute, and the Breast Cancer Research Foundation. Dr. Cohen reported having no conflicts of interest. Dr. Wagle is an equity holder in Foundation Medicine, a consultant to Novartis, and a recipient of sponsored research support from Novartis, Genentech, and Merck.
SAN ANTONIO – The “genomic landscape” of resistant estrogen receptor–positive (ER+) metastatic breast cancer differs significantly from that of ER+ primary breast cancer, according to findings from a study involving whole-exome sequencing and transcriptome sequencing of such cancers.
Multiple genes were recurrently altered in ER+ metastatic breast cancers at a rate significantly higher than in ER+ primary breast cancers (with 3- to 33-fold enrichment in metastatic vs. primary samples), Ofir Cohen, PhD, explained at the San Antonio Breast Cancer Symposium.
This finding, which suggests that recurrent alterations in genes in ER+ metastatic breast cancers are often acquired after treatment and thus may play a role in resistance to ER-directed therapies and/or metastasis, highlights the value of genomic profiling of metastatic biopsies and has implications for drug development, said Dr. Cohen of the Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard in Cambridge.
Although the genomic and molecular landscape of ER+ primary breast cancer is better understood, that of ER+ metastatic breast cancer is underexplored, he noted.
Thus, he and his colleagues performed whole-exome sequencing on 149 metastatic tumor biopsies from patients with ER+ metastatic tumors and resistance to at least one ER-directed therapy and compared the results with those from 44 matched primary samples from the same patient. They also performed transcriptome sequencing (RNA-seq) of 128 metastatic biopsies.
A key observation from the study is that ESR1 genes were mutated in 24% of the cohort, and the mutations were acquired in 14 of the 15 samples with matched primary samples.
“This emphasized the important role that these mutations may play, specifically in the metastatic and drug-resistant settings,” Dr. Cohen said.
Similarly, ERBB2 mutations occurred in 7% of samples, and seemed to be acquired in five of six metastatic samples with matched primary samples, he said.
“For both of these genes, other than being acquired and suggestive of importance, they also have clear clinical implications, as finding those mutations may guide treatment choices for those patients,” he said.
Another example involves RB1 mutations, which were found in 5% of samples, and which appeared to be acquired in three of five of those with matched primaries. More frequent alterations were also found in PIK3CA, PTEN, and AKTI genes, among others, in metastatic vs. primary cancers.
The observation that these tumors evolve and have different mutations in the primary and metastatic settings may be important, because this suggests that knowledge of the alterations and mutations in the primary setting is insufficient to guide treatment in the metastatic setting.
“So the take-home message here is that tumors do evolve, and that the metastatic setting is different than the primary setting,” Dr. Cohen said.
Sequencing both the exome and the transcriptome may “give us a handle to assess that,” he said.
“Our goal is really to understand evolved resistance. That is, to try and understand the mechanisms that drive the evolution of resistance in ER+ metastatic breast cancer, and, once we understand that, [to determine] how we can translate that knowledge in the clinic,” he said, noting that resistance also may develop through other nongenomic mechanisms, such as epigenetic and regulatory mechanisms.
“As long as those mechanisms leave a footprint on the transcriptome … sequencing the transcriptome together with the exome may yield relevant insights into resistance states that do not derive specifically from exome mutations,” he added.
The findings are important because, despite tremendous advances in the treatment of ER+ metastatic breast cancer, therapeutic resistance remains a common problem, and improved understanding of the underlying resistance mechanisms is critical for enabling durable control of this disease, Dr. Cohen said, explaining that resistant tumors remain the most common cause of breast cancer death and that there is an urgent need to develop new therapeutic strategies for patients who no longer respond to existing therapies.
In a written statement, senior investigator Nikhil Wagle, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston, said that the ultimate goal of the project is “to integrate the functional and clinical findings into a unified ‘Resistance Atlas’ for ER+ metastatic breast cancer, which should help inform treatment decisions for individual patients as well as propel the development of new combination treatment strategies for ER-positive metastatic breast cancer.”
This study was funded by the National Cancer Institute, the National Human Genome Research Institute, the Department of Defense Breast Cancer Research Program, Susan G. Komen, the V Foundation, the Breast Cancer Alliance, the AACR-Landon Foundation, the Friends of Dana-Farber Cancer Institute, and the Breast Cancer Research Foundation. Dr. Cohen reported having no conflicts of interest. Dr. Wagle is an equity holder in Foundation Medicine, a consultant to Novartis, and a recipient of sponsored research support from Novartis, Genentech, and Merck.
AT SABCS 2016
Key clinical point:
Major finding: ESR1 genes were mutated in 24% of the cohort, and the mutations were acquired in 14 of the 15 samples with matched primary samples.
Data source: Whole-exome sequencing of 149 metastatic breast cancer biopsies and 44 matched primary tumor biopsies, and transcriptome sequencing of 128 metastatic biopsies.
Disclosures: This study was funded by the National Cancer Institute, the National Human Genome Research Institute, the Department of Defense Breast Cancer Research Program, Susan G. Komen, the V Foundation, the Breast Cancer Alliance, the AACR-Landon Foundation, the Friends of Dana-Farber Cancer Institute, and the Breast Cancer Research Foundation. Dr. Cohen reported having no conflicts of interest. Dr. Wagle is an equity holder in Foundation Medicine, a consultant to Novartis, and a recipient of sponsored research support from Novartis, Genentech, and Merck.
VIDEO: Veliparib misses PFS endpoint, advances to phase III trial
SAN ANTONIO – The investigational selective PARP-1 and PARP-2 inhibitor veliparib failed to significantly improve progression-free or overall survival, compared with placebo, when added to carboplatin and paclitaxel in patients with BRCA1 or BRCA2 mutations and locally recurrent or metastatic breast cancer in the randomized phase II BROCADE study.
The potent, orally bioavailable drug did, however, show a trend toward improvement on these measures, as well as a significant improvement in overall response-rate findings that warrant further investigation in a phase III trial, Hyo Han, MD, said at the San Antonio Breast Cancer Symposium.
Patients were randomized to receive placebo (98 patients) or 120 mg veliparib twice daily on days 1-7 (95 patients) in addition to carboplatin and 175 mg/m2 of paclitaxel every 3 weeks.
Median progression-free survival – the primary endpoint of the study – was 12.3 months in the placebo group and 14.1 months in the veliparib group (hazard ratio, 0.789), and overall survival was 25.9 and 28.3 months, respectively (HR, 0.750), said Dr. Han of Moffitt Cancer Center, Tampa, Fla.
The overall response rate was 61.3% vs. 77.8% in the groups, respectively.
Although the study did not meet its primary endpoint, the findings are encouraging as it was powered to detect only dramatic differences between the groups, Dr. Han said.
In a video interview, she discussed veliparib, its safety, the BROCADE findings – including data from a third study arm looking at veliparib in combination with temozolomide, and plans for evaluating veliparib in the ongoing phase III BROCADE3 trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – The investigational selective PARP-1 and PARP-2 inhibitor veliparib failed to significantly improve progression-free or overall survival, compared with placebo, when added to carboplatin and paclitaxel in patients with BRCA1 or BRCA2 mutations and locally recurrent or metastatic breast cancer in the randomized phase II BROCADE study.
The potent, orally bioavailable drug did, however, show a trend toward improvement on these measures, as well as a significant improvement in overall response-rate findings that warrant further investigation in a phase III trial, Hyo Han, MD, said at the San Antonio Breast Cancer Symposium.
Patients were randomized to receive placebo (98 patients) or 120 mg veliparib twice daily on days 1-7 (95 patients) in addition to carboplatin and 175 mg/m2 of paclitaxel every 3 weeks.
Median progression-free survival – the primary endpoint of the study – was 12.3 months in the placebo group and 14.1 months in the veliparib group (hazard ratio, 0.789), and overall survival was 25.9 and 28.3 months, respectively (HR, 0.750), said Dr. Han of Moffitt Cancer Center, Tampa, Fla.
The overall response rate was 61.3% vs. 77.8% in the groups, respectively.
Although the study did not meet its primary endpoint, the findings are encouraging as it was powered to detect only dramatic differences between the groups, Dr. Han said.
In a video interview, she discussed veliparib, its safety, the BROCADE findings – including data from a third study arm looking at veliparib in combination with temozolomide, and plans for evaluating veliparib in the ongoing phase III BROCADE3 trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – The investigational selective PARP-1 and PARP-2 inhibitor veliparib failed to significantly improve progression-free or overall survival, compared with placebo, when added to carboplatin and paclitaxel in patients with BRCA1 or BRCA2 mutations and locally recurrent or metastatic breast cancer in the randomized phase II BROCADE study.
The potent, orally bioavailable drug did, however, show a trend toward improvement on these measures, as well as a significant improvement in overall response-rate findings that warrant further investigation in a phase III trial, Hyo Han, MD, said at the San Antonio Breast Cancer Symposium.
Patients were randomized to receive placebo (98 patients) or 120 mg veliparib twice daily on days 1-7 (95 patients) in addition to carboplatin and 175 mg/m2 of paclitaxel every 3 weeks.
Median progression-free survival – the primary endpoint of the study – was 12.3 months in the placebo group and 14.1 months in the veliparib group (hazard ratio, 0.789), and overall survival was 25.9 and 28.3 months, respectively (HR, 0.750), said Dr. Han of Moffitt Cancer Center, Tampa, Fla.
The overall response rate was 61.3% vs. 77.8% in the groups, respectively.
Although the study did not meet its primary endpoint, the findings are encouraging as it was powered to detect only dramatic differences between the groups, Dr. Han said.
In a video interview, she discussed veliparib, its safety, the BROCADE findings – including data from a third study arm looking at veliparib in combination with temozolomide, and plans for evaluating veliparib in the ongoing phase III BROCADE3 trial.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2016
Fulvestrant/everolimus improves PFS in HR+, HER2– advanced breast cancer
SAN ANTONIO – Adding everolimus to fulvestrant doubled median progression-free survival among postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer resistant to therapy with an aromatase inhibitor [AI] in the PrECOG 0102 study.
In the randomized phase II trial, the combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) with the selective estrogen receptor down-regulator [SERD] fulvestrant (Faslodex) was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo, reported Noah S. Kornblum, MD, of Montefiore Einstein Center for Cancer Care, New York.
This study provides additional evidence that adding everolimus to anti-estrogen therapy in AI-resistant disease improves clinical outcomes,” he said at the San Antonio Breast Cancer Symposium.
Most women with hormone receptor–positive breast cancer treated with an AI will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus to a steroid AI, exemestane (Aromasin), as in the BOLERO-2 trial.
“Another strategy for overcoming AI resistance is by more completely blocking estrogen-receptor signaling through the use of a selective estrogen receptor down-regulator, which may result in more complete blockade of the ER signaling pathway than a steroidal AI such as exemestane,” Dr. Kornblum said.
To test this hypothesis, the investigators enrolled 131 postmenopausal women with inoperable locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer resistant to AIs.
AI resistance was defined as relapse while receiving adjuvant AI therapy, and/or progression after one or more AIs for metastatic disease. The patients could have had no more than one prior chemotherapy regimen for metastatic disease.
The patients were stratified by Eastern Cooperative Oncology Group performance status, presence of measurable disease, and prior chemotherapy status, and were then randomized to receive either high-dose fulvestrant (500 mg on day 1 and 15 of cycle 1, and then on day 1 of cycles 2-12) plus oral everolimus 10 mg/day, or fulvestrant and placebo.
The trial had an induction phase, in which patients were treated until evidence of progressive disease or unacceptable toxicity for a maximum of 12 28-day cycles, and a continuation phase in which patients who had neither disease progression nor experienced unacceptable toxicities could have their data unblinded and could continue on fulvestrant/everolimus.
The trial did not include the use of corticosteroid-containing mouthwash for prevention of treatment-associated stomatitis, because the trial was designed before the evidence of the benefit of such prophylaxis became public, Dr. Kornblum said.
As noted before, the primary endpoint of PFS by investigator assessment was significantly better with the combination, at 10.4 vs. 5.1 months for the fulvestrant/placebo group. The hazard ratio was 0.60 (P = .02).
There was no difference in overall survival (OS), however. Median OS was 24.8 months among patients treated with everolimus, compared with not yet reached in the placebo arm (not statistically significant).
The combination was associated with more grade 3 adverse events than fulvestrant/placebo (48% vs. 14%, respectively). The most common grade 3 adverse events occurring in more than 5% of patients were stomatitis, pneumonitis, fatigue and hyperglycemia. Overall, the safety profile of the combination was consistent with that seen in BOLERO-2, Dr. Kornblum said.
In all, 10% of patients assigned to the combination and 12% assigned to placebo withdrew from the study because of adverse events; these patients were included in the analysis, which was by intention-to-treat.
Regarding future directions, Dr. Kornblum noted that “our study was completed prior to the availability of the CD4/6 inhibitors, which are effective added to both first-line AI therapy or second-line fulvestrant in AI-resistant disease. On the other hand, mTOR inhibitors are effective as second line therapy in AI-resistant disease, but possibly not as first-line therapy.”
As only a few patients in the study received a prior CDK4/6 inhibitor, “further work is required to define whether prior CDk4/6 inhibitor therapy would impact response to combination mTOR-inhibitor/SERD therapy,” he added.
Potential role for the combination?
Following the presentation, SABCS fixture Steven “Vogl, New York” Vogl, MD, asked what to do when fulvestrant-based therapy fails.*
“I’m interested in what to do after progression. Let’s say the patient gets fulvestrant, gets everolimus, has a nice response – 9 months later, the tumor gets worse. We’re all pretty sure we shouldn’t continue the fulvestrant. I would love PrECOG to do a study in those patients of giving megestrol or megestrol/everolimus, and see if the everolimus extended beyond progression does the patient some good, as does trastuzumab,” he said.
“Sounds like a good idea. I’m game, let’s roll up our sleeves and do it together,” Dr. Kornblum replied.
The study was sponsored by PrECOG with financial support from Novartis. Dr. Kornblum reported having no conflicts of interest.
Correction 12/8/16: An earlier version of this article misstated Dr. Steven Vogl's name.
SAN ANTONIO – Adding everolimus to fulvestrant doubled median progression-free survival among postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer resistant to therapy with an aromatase inhibitor [AI] in the PrECOG 0102 study.
In the randomized phase II trial, the combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) with the selective estrogen receptor down-regulator [SERD] fulvestrant (Faslodex) was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo, reported Noah S. Kornblum, MD, of Montefiore Einstein Center for Cancer Care, New York.
This study provides additional evidence that adding everolimus to anti-estrogen therapy in AI-resistant disease improves clinical outcomes,” he said at the San Antonio Breast Cancer Symposium.
Most women with hormone receptor–positive breast cancer treated with an AI will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus to a steroid AI, exemestane (Aromasin), as in the BOLERO-2 trial.
“Another strategy for overcoming AI resistance is by more completely blocking estrogen-receptor signaling through the use of a selective estrogen receptor down-regulator, which may result in more complete blockade of the ER signaling pathway than a steroidal AI such as exemestane,” Dr. Kornblum said.
To test this hypothesis, the investigators enrolled 131 postmenopausal women with inoperable locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer resistant to AIs.
AI resistance was defined as relapse while receiving adjuvant AI therapy, and/or progression after one or more AIs for metastatic disease. The patients could have had no more than one prior chemotherapy regimen for metastatic disease.
The patients were stratified by Eastern Cooperative Oncology Group performance status, presence of measurable disease, and prior chemotherapy status, and were then randomized to receive either high-dose fulvestrant (500 mg on day 1 and 15 of cycle 1, and then on day 1 of cycles 2-12) plus oral everolimus 10 mg/day, or fulvestrant and placebo.
The trial had an induction phase, in which patients were treated until evidence of progressive disease or unacceptable toxicity for a maximum of 12 28-day cycles, and a continuation phase in which patients who had neither disease progression nor experienced unacceptable toxicities could have their data unblinded and could continue on fulvestrant/everolimus.
The trial did not include the use of corticosteroid-containing mouthwash for prevention of treatment-associated stomatitis, because the trial was designed before the evidence of the benefit of such prophylaxis became public, Dr. Kornblum said.
As noted before, the primary endpoint of PFS by investigator assessment was significantly better with the combination, at 10.4 vs. 5.1 months for the fulvestrant/placebo group. The hazard ratio was 0.60 (P = .02).
There was no difference in overall survival (OS), however. Median OS was 24.8 months among patients treated with everolimus, compared with not yet reached in the placebo arm (not statistically significant).
The combination was associated with more grade 3 adverse events than fulvestrant/placebo (48% vs. 14%, respectively). The most common grade 3 adverse events occurring in more than 5% of patients were stomatitis, pneumonitis, fatigue and hyperglycemia. Overall, the safety profile of the combination was consistent with that seen in BOLERO-2, Dr. Kornblum said.
In all, 10% of patients assigned to the combination and 12% assigned to placebo withdrew from the study because of adverse events; these patients were included in the analysis, which was by intention-to-treat.
Regarding future directions, Dr. Kornblum noted that “our study was completed prior to the availability of the CD4/6 inhibitors, which are effective added to both first-line AI therapy or second-line fulvestrant in AI-resistant disease. On the other hand, mTOR inhibitors are effective as second line therapy in AI-resistant disease, but possibly not as first-line therapy.”
As only a few patients in the study received a prior CDK4/6 inhibitor, “further work is required to define whether prior CDk4/6 inhibitor therapy would impact response to combination mTOR-inhibitor/SERD therapy,” he added.
Potential role for the combination?
Following the presentation, SABCS fixture Steven “Vogl, New York” Vogl, MD, asked what to do when fulvestrant-based therapy fails.*
“I’m interested in what to do after progression. Let’s say the patient gets fulvestrant, gets everolimus, has a nice response – 9 months later, the tumor gets worse. We’re all pretty sure we shouldn’t continue the fulvestrant. I would love PrECOG to do a study in those patients of giving megestrol or megestrol/everolimus, and see if the everolimus extended beyond progression does the patient some good, as does trastuzumab,” he said.
“Sounds like a good idea. I’m game, let’s roll up our sleeves and do it together,” Dr. Kornblum replied.
The study was sponsored by PrECOG with financial support from Novartis. Dr. Kornblum reported having no conflicts of interest.
Correction 12/8/16: An earlier version of this article misstated Dr. Steven Vogl's name.
SAN ANTONIO – Adding everolimus to fulvestrant doubled median progression-free survival among postmenopausal women with hormone-receptor positive, human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer resistant to therapy with an aromatase inhibitor [AI] in the PrECOG 0102 study.
In the randomized phase II trial, the combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) with the selective estrogen receptor down-regulator [SERD] fulvestrant (Faslodex) was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo, reported Noah S. Kornblum, MD, of Montefiore Einstein Center for Cancer Care, New York.
This study provides additional evidence that adding everolimus to anti-estrogen therapy in AI-resistant disease improves clinical outcomes,” he said at the San Antonio Breast Cancer Symposium.
Most women with hormone receptor–positive breast cancer treated with an AI will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus to a steroid AI, exemestane (Aromasin), as in the BOLERO-2 trial.
“Another strategy for overcoming AI resistance is by more completely blocking estrogen-receptor signaling through the use of a selective estrogen receptor down-regulator, which may result in more complete blockade of the ER signaling pathway than a steroidal AI such as exemestane,” Dr. Kornblum said.
To test this hypothesis, the investigators enrolled 131 postmenopausal women with inoperable locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer resistant to AIs.
AI resistance was defined as relapse while receiving adjuvant AI therapy, and/or progression after one or more AIs for metastatic disease. The patients could have had no more than one prior chemotherapy regimen for metastatic disease.
The patients were stratified by Eastern Cooperative Oncology Group performance status, presence of measurable disease, and prior chemotherapy status, and were then randomized to receive either high-dose fulvestrant (500 mg on day 1 and 15 of cycle 1, and then on day 1 of cycles 2-12) plus oral everolimus 10 mg/day, or fulvestrant and placebo.
The trial had an induction phase, in which patients were treated until evidence of progressive disease or unacceptable toxicity for a maximum of 12 28-day cycles, and a continuation phase in which patients who had neither disease progression nor experienced unacceptable toxicities could have their data unblinded and could continue on fulvestrant/everolimus.
The trial did not include the use of corticosteroid-containing mouthwash for prevention of treatment-associated stomatitis, because the trial was designed before the evidence of the benefit of such prophylaxis became public, Dr. Kornblum said.
As noted before, the primary endpoint of PFS by investigator assessment was significantly better with the combination, at 10.4 vs. 5.1 months for the fulvestrant/placebo group. The hazard ratio was 0.60 (P = .02).
There was no difference in overall survival (OS), however. Median OS was 24.8 months among patients treated with everolimus, compared with not yet reached in the placebo arm (not statistically significant).
The combination was associated with more grade 3 adverse events than fulvestrant/placebo (48% vs. 14%, respectively). The most common grade 3 adverse events occurring in more than 5% of patients were stomatitis, pneumonitis, fatigue and hyperglycemia. Overall, the safety profile of the combination was consistent with that seen in BOLERO-2, Dr. Kornblum said.
In all, 10% of patients assigned to the combination and 12% assigned to placebo withdrew from the study because of adverse events; these patients were included in the analysis, which was by intention-to-treat.
Regarding future directions, Dr. Kornblum noted that “our study was completed prior to the availability of the CD4/6 inhibitors, which are effective added to both first-line AI therapy or second-line fulvestrant in AI-resistant disease. On the other hand, mTOR inhibitors are effective as second line therapy in AI-resistant disease, but possibly not as first-line therapy.”
As only a few patients in the study received a prior CDK4/6 inhibitor, “further work is required to define whether prior CDk4/6 inhibitor therapy would impact response to combination mTOR-inhibitor/SERD therapy,” he added.
Potential role for the combination?
Following the presentation, SABCS fixture Steven “Vogl, New York” Vogl, MD, asked what to do when fulvestrant-based therapy fails.*
“I’m interested in what to do after progression. Let’s say the patient gets fulvestrant, gets everolimus, has a nice response – 9 months later, the tumor gets worse. We’re all pretty sure we shouldn’t continue the fulvestrant. I would love PrECOG to do a study in those patients of giving megestrol or megestrol/everolimus, and see if the everolimus extended beyond progression does the patient some good, as does trastuzumab,” he said.
“Sounds like a good idea. I’m game, let’s roll up our sleeves and do it together,” Dr. Kornblum replied.
The study was sponsored by PrECOG with financial support from Novartis. Dr. Kornblum reported having no conflicts of interest.
Correction 12/8/16: An earlier version of this article misstated Dr. Steven Vogl's name.
AT SABCS 2016
Key clinical point: This study provides further evidence of the benefits of adding an mTOR inhibitor to anti-hormonal therapy in postmenopausal women with advanced breast cancer resistant to aromatase inhibitors.
Major finding: Fulvestrant/everolimus was associated with progression-free survival of 10.4 months, vs. 5.1 months for fulvestrant/placebo.
Data source: Randomized phase II trial of 131 women with hormone-receptor positive, HER2-negative locally advanced of metastatic breast cancer resistant to aromatase inhibitors.
Disclosures: The study was sponsored by PrECOG with financial support from Novartis. Dr. Kornblum reported having no conflicts of interest.
VIDEO: Investigator discusses fulvestrant/everolimus combo
SAN ANTONIO – Most women with hormone receptor–positive breast cancer treated with an aromatase inhibitor will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus (Affinitor) to a steroidal aromatase inhibitor (AI) such as exemestane (Aromasin), as in the BOLERO-2 trial.
Alternatively, blocking estrogen-receptor signaling through the use of a selective estrogen receptor down regulator, such as fulvestrant (Faslodex), may result in more complete blockade of the ER signaling pathway than would a steroidal AI such as exemestane.
In this video interview at the San Antonio Breast Cancer Symposium, Noah S. Kornblum, MD, of the Montefiore-Einstein Center for Cancer Care, New York, discusses findings from the phase II PrECOG 0102 trial comparing a combination of fulvestrant and everolimus to fulvestrant and placebo for the treatment of postmenopausal women with hormone receptor–positive, HER2-negative breast cancer resistant to AI therapy.
The combination was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo (hazard ratio, 0.60; P = .02).
Dr. Kornblum says that the study provides additional evidence for adding everolimus to anti-estrogen therapy in AI-resistant disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Most women with hormone receptor–positive breast cancer treated with an aromatase inhibitor will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus (Affinitor) to a steroidal aromatase inhibitor (AI) such as exemestane (Aromasin), as in the BOLERO-2 trial.
Alternatively, blocking estrogen-receptor signaling through the use of a selective estrogen receptor down regulator, such as fulvestrant (Faslodex), may result in more complete blockade of the ER signaling pathway than would a steroidal AI such as exemestane.
In this video interview at the San Antonio Breast Cancer Symposium, Noah S. Kornblum, MD, of the Montefiore-Einstein Center for Cancer Care, New York, discusses findings from the phase II PrECOG 0102 trial comparing a combination of fulvestrant and everolimus to fulvestrant and placebo for the treatment of postmenopausal women with hormone receptor–positive, HER2-negative breast cancer resistant to AI therapy.
The combination was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo (hazard ratio, 0.60; P = .02).
Dr. Kornblum says that the study provides additional evidence for adding everolimus to anti-estrogen therapy in AI-resistant disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN ANTONIO – Most women with hormone receptor–positive breast cancer treated with an aromatase inhibitor will eventually develop resistance to these agents. Strategies for overcoming resistance include the addition of everolimus (Affinitor) to a steroidal aromatase inhibitor (AI) such as exemestane (Aromasin), as in the BOLERO-2 trial.
Alternatively, blocking estrogen-receptor signaling through the use of a selective estrogen receptor down regulator, such as fulvestrant (Faslodex), may result in more complete blockade of the ER signaling pathway than would a steroidal AI such as exemestane.
In this video interview at the San Antonio Breast Cancer Symposium, Noah S. Kornblum, MD, of the Montefiore-Einstein Center for Cancer Care, New York, discusses findings from the phase II PrECOG 0102 trial comparing a combination of fulvestrant and everolimus to fulvestrant and placebo for the treatment of postmenopausal women with hormone receptor–positive, HER2-negative breast cancer resistant to AI therapy.
The combination was associated with a median progression-free survival of 10.4 months, compared with 5.1 months for fulvestrant plus placebo (hazard ratio, 0.60; P = .02).
Dr. Kornblum says that the study provides additional evidence for adding everolimus to anti-estrogen therapy in AI-resistant disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT SABCS 2016
SABCS 2016: Top picks from Dr. Hope S. Rugo and Dr. William J. Gradishar
Oncology Practice associate editors Dr. Hope S. Rugo and Dr. William J. Gradishar reveal several anticipated studies from the 39th annual San Antonio Breast Cancer Symposium, set to begin on Wednesday, Dec. 7:
• S1-02. PrECOG 0102. A randomized, double-blind, phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer resistant to aromatase inhibitor therapy
• S1-03. First results from the multicenter phase III DATA study comparing 3 vs. 6 years of anastrozole after 2-3 years of tamoxifen in postmenopausal women with HR–positive early breast cancer.
• S1-04. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05).
• S1-05. A randomized, double-blind, placebo-controlled clinical trial to evaluate extended adjuvant endocrine therapy (5 years of letrozole) in postmenopausal women with HR–positive breast cancer who have completed previous adjuvant endocrine therapy: initial results of NRG oncology/NSABP B-42.
• S1-08. Prognostic associations of tumor-infiltrating lymphocytes in metastatic HER2-positive breast cancer treated with trastuzumab and pertuzumab: a secondary analysis of the CLEOPATRA study.
• S2-03. Does BRCA status affect outcome in young breast cancer patients? Results from the Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer (POSH).
• S2-05. Efficacy and tolerability of veliparib (ABT-888) in combination with carboplatin (C) and paclitaxel (P) vs. placebo (Plc)+C/P in patients with BRCA1 or BRCA2 mutations and metastatic breast cancer: a randomized, phase II study.
• S2-06. DNA repair deficiency biomarkers and MammaPrint High1/(ultra)High2 risk as predictors of veliparib/carboplatin response: results from the neoadjuvant I-SPY 2 trial for high-risk breast cancer.
• S3-02. Plasma microRNA levels for predicting therapeutic response to neoadjuvant treatment in HER2-positive breast cancer: results from Neo-ALTTO.
• S3-04. Primary analysis of PERTAIN: a randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in first-line patients with HER2-positive and HR–positive metastatic or locally advanced breast cancer.
• S4-06. Biologic effects of abemaciclib in a phase II neoadjuvant study for postmenopausal patients with HR–positive, HER2-negative breast cancer.
• S4-07. BELLE-3: a phase III study of buparlisib + fulvestrant in postmenopausal women with HR-positive, HER2-negative, aromatase inhibitor–treated locally advanced or metastatic breast cancer, who progressed on or after mTOR inhibitor–based treatment.
• S5-02. Scalp Cooling Alopecia Prevention (SCALP) trial for patients with early-stage breast cancer.
Dr. Rugo is professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center. Dr. Gradishar is the Betsy Bramsen Professor of Breast Oncology, professor of medicine, and deputy chief in the division of hematology/oncology, Feinberg School of Medicine, Chicago; and deputy director for the Clinical Network and director of the Maggie Daley Center for Women’s Cancer Care, Robert H. Lurie Comprehensive Cancer Center Network of Northwestern University, Chicago.
Oncology Practice associate editors Dr. Hope S. Rugo and Dr. William J. Gradishar reveal several anticipated studies from the 39th annual San Antonio Breast Cancer Symposium, set to begin on Wednesday, Dec. 7:
• S1-02. PrECOG 0102. A randomized, double-blind, phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer resistant to aromatase inhibitor therapy
• S1-03. First results from the multicenter phase III DATA study comparing 3 vs. 6 years of anastrozole after 2-3 years of tamoxifen in postmenopausal women with HR–positive early breast cancer.
• S1-04. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05).
• S1-05. A randomized, double-blind, placebo-controlled clinical trial to evaluate extended adjuvant endocrine therapy (5 years of letrozole) in postmenopausal women with HR–positive breast cancer who have completed previous adjuvant endocrine therapy: initial results of NRG oncology/NSABP B-42.
• S1-08. Prognostic associations of tumor-infiltrating lymphocytes in metastatic HER2-positive breast cancer treated with trastuzumab and pertuzumab: a secondary analysis of the CLEOPATRA study.
• S2-03. Does BRCA status affect outcome in young breast cancer patients? Results from the Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer (POSH).
• S2-05. Efficacy and tolerability of veliparib (ABT-888) in combination with carboplatin (C) and paclitaxel (P) vs. placebo (Plc)+C/P in patients with BRCA1 or BRCA2 mutations and metastatic breast cancer: a randomized, phase II study.
• S2-06. DNA repair deficiency biomarkers and MammaPrint High1/(ultra)High2 risk as predictors of veliparib/carboplatin response: results from the neoadjuvant I-SPY 2 trial for high-risk breast cancer.
• S3-02. Plasma microRNA levels for predicting therapeutic response to neoadjuvant treatment in HER2-positive breast cancer: results from Neo-ALTTO.
• S3-04. Primary analysis of PERTAIN: a randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in first-line patients with HER2-positive and HR–positive metastatic or locally advanced breast cancer.
• S4-06. Biologic effects of abemaciclib in a phase II neoadjuvant study for postmenopausal patients with HR–positive, HER2-negative breast cancer.
• S4-07. BELLE-3: a phase III study of buparlisib + fulvestrant in postmenopausal women with HR-positive, HER2-negative, aromatase inhibitor–treated locally advanced or metastatic breast cancer, who progressed on or after mTOR inhibitor–based treatment.
• S5-02. Scalp Cooling Alopecia Prevention (SCALP) trial for patients with early-stage breast cancer.
Dr. Rugo is professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center. Dr. Gradishar is the Betsy Bramsen Professor of Breast Oncology, professor of medicine, and deputy chief in the division of hematology/oncology, Feinberg School of Medicine, Chicago; and deputy director for the Clinical Network and director of the Maggie Daley Center for Women’s Cancer Care, Robert H. Lurie Comprehensive Cancer Center Network of Northwestern University, Chicago.
Oncology Practice associate editors Dr. Hope S. Rugo and Dr. William J. Gradishar reveal several anticipated studies from the 39th annual San Antonio Breast Cancer Symposium, set to begin on Wednesday, Dec. 7:
• S1-02. PrECOG 0102. A randomized, double-blind, phase II trial of fulvestrant plus everolimus or placebo in postmenopausal women with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer resistant to aromatase inhibitor therapy
• S1-03. First results from the multicenter phase III DATA study comparing 3 vs. 6 years of anastrozole after 2-3 years of tamoxifen in postmenopausal women with HR–positive early breast cancer.
• S1-04. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05).
• S1-05. A randomized, double-blind, placebo-controlled clinical trial to evaluate extended adjuvant endocrine therapy (5 years of letrozole) in postmenopausal women with HR–positive breast cancer who have completed previous adjuvant endocrine therapy: initial results of NRG oncology/NSABP B-42.
• S1-08. Prognostic associations of tumor-infiltrating lymphocytes in metastatic HER2-positive breast cancer treated with trastuzumab and pertuzumab: a secondary analysis of the CLEOPATRA study.
• S2-03. Does BRCA status affect outcome in young breast cancer patients? Results from the Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer (POSH).
• S2-05. Efficacy and tolerability of veliparib (ABT-888) in combination with carboplatin (C) and paclitaxel (P) vs. placebo (Plc)+C/P in patients with BRCA1 or BRCA2 mutations and metastatic breast cancer: a randomized, phase II study.
• S2-06. DNA repair deficiency biomarkers and MammaPrint High1/(ultra)High2 risk as predictors of veliparib/carboplatin response: results from the neoadjuvant I-SPY 2 trial for high-risk breast cancer.
• S3-02. Plasma microRNA levels for predicting therapeutic response to neoadjuvant treatment in HER2-positive breast cancer: results from Neo-ALTTO.
• S3-04. Primary analysis of PERTAIN: a randomized, two-arm, open-label, multicenter phase II trial assessing the efficacy and safety of pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in first-line patients with HER2-positive and HR–positive metastatic or locally advanced breast cancer.
• S4-06. Biologic effects of abemaciclib in a phase II neoadjuvant study for postmenopausal patients with HR–positive, HER2-negative breast cancer.
• S4-07. BELLE-3: a phase III study of buparlisib + fulvestrant in postmenopausal women with HR-positive, HER2-negative, aromatase inhibitor–treated locally advanced or metastatic breast cancer, who progressed on or after mTOR inhibitor–based treatment.
• S5-02. Scalp Cooling Alopecia Prevention (SCALP) trial for patients with early-stage breast cancer.
Dr. Rugo is professor of medicine, University of California, San Francisco, and director, breast oncology and clinical trials education, UCSF Helen Diller Family Comprehensive Cancer Center. Dr. Gradishar is the Betsy Bramsen Professor of Breast Oncology, professor of medicine, and deputy chief in the division of hematology/oncology, Feinberg School of Medicine, Chicago; and deputy director for the Clinical Network and director of the Maggie Daley Center for Women’s Cancer Care, Robert H. Lurie Comprehensive Cancer Center Network of Northwestern University, Chicago.
FROM SABCS 2016