Breast Cancer

CHICAGO – Extending adjuvant aromatase inhibitor treatment out to a decade reduced the risk of recurrence and the risk of a new breast cancer in postmenopausal women treated for early-stage breast cancer, Dr. Paul Goss reported at the annual meeting of the American Society of Clinical Oncology.

Women taking letrozole for five additional years had a 34% lower risk of disease-free survival events than those who received placebo, data from MA.17R showed. The annual incidence of contralateral breast cancer was .21% with extended letrozole vs. .49% with placebo. There was no difference in overall survival.

In an interview at the meeting, Dr. Goss discusses the “profoundly important result” and says doctors should be challenged if choosing not to extend treatment for their patients.

CHICAGO – Extending adjuvant aromatase inhibitor treatment out to a decade reduced the risk of recurrence and the risk of a new breast cancer in postmenopausal women treated for early-stage breast cancer, Dr. Paul Goss reported at the annual meeting of the American Society of Clinical Oncology.

Women taking letrozole for five additional years had a 34% lower risk of disease-free survival events than those who received placebo, data from MA.17R showed. The annual incidence of contralateral breast cancer was .21% with extended letrozole vs. .49% with placebo. There was no difference in overall survival.

In an interview at the meeting, Dr. Goss discusses the “profoundly important result” and says doctors should be challenged if choosing not to extend treatment for their patients.

CHICAGO – Extending adjuvant aromatase inhibitor treatment out to a decade reduced the risk of recurrence and the risk of a new breast cancer in postmenopausal women treated for early-stage breast cancer, Dr. Paul Goss reported at the annual meeting of the American Society of Clinical Oncology.

Women taking letrozole for five additional years had a 34% lower risk of disease-free survival events than those who received placebo, data from MA.17R showed. The annual incidence of contralateral breast cancer was .21% with extended letrozole vs. .49% with placebo. There was no difference in overall survival.

In an interview at the meeting, Dr. Goss discusses the “profoundly important result” and says doctors should be challenged if choosing not to extend treatment for their patients.

Chicago – Young black women with breast cancer are much less likely than white or Hispanic women to undergo testing for BRCA gene mutations, which puts them also at risk for ovarian cancer. And if they carry a BRCA mutation, they are much less likely to undergo removal of their ovaries and fallopian tubes.

Carriers of BRCA mutations have a high lifetime risk of breast and ovarian cancers – up to 60%-70% risk of developing breast cancer, up to 44% risk for ovarian cancer, and a 50% or greater risk for a secondary breast cancer after a first breast cancer diagnosis. Breast cancer risk management may consist of periodic screening or prophylactic mastectomy. But because there are no reliable screening methods for ovarian cancer, the main option for risk management is surgical.At the American Society of Clinical Oncology annual meeting, Dr. Tuya Pal said, “It is very important to think about the benefits of detecting a BRCA mutation. It’s not really about getting them tested, but the health benefit arises from doing something with that information.”

For a population-based, cross-sectional study to investigate women’s receipt of BRCA testing and the uptake of preventive surgery among BRCA mutation carriers, she recruited 440 black, 284 Hispanic, and 897 non-Hispanic white breast cancer survivors through the Florida State Cancer Registry. The study included women who had been diagnosed with invasive breast cancer at up to age 50 years between 2009 and 2012, who completed a baseline survey.

“Among our black women, 36% had received BRCA testing at the time of study recruitment compared with 62% of the Hispanic women and 65% of the non-Hispanic white women,” said Dr. Pal, a clinical geneticist at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla. Even after controlling for meeting high-risk criteria based on national practice guidelines, socioeconomic status variables, and provider referral patterns, there were still significant disparities in BRCA testing (P = .025) for black women, compared with the other two groups.

Of the 1,621 women in the study, 917 (57%) reported BRCA testing, of whom 92 (10%) tested positive for the mutation (28 Black, 13 Hispanic, and 51 non-Hispanic White).

The pattern of ethnic disparity persisted for cancer risk management practices among women with the gene mutation, with 68% of black women opting for bilateral mastectomy vs. 85% of Hispanic women and 94% of non-Hispanic whites. Because mastectomy is not the only form of risk management, Dr. Pal also looked at the rates of breast cancer screening in these women.

“That brought us up to 86% with the black women, 100% among Hispanic women, and 98% among the white women,” she said. However, three out of four of the Black women who did not use any risk management techniques were still in treatment, so it was too early to see what they would do.

For salpingo-oophorectomy, the rates were 32% of black, 85% of Hispanic, and 71% of non-Hispanic white women. After controlling for age at enrollment, time since diagnosis, income, family medical history, and insurance status, there were still disparities between black women and Hispanic women (P = .01) and between black and white women (P = .02).

Even in light of these findings that black women are much less likely to have BRCA testing and to undergo salpingo-oophorectomy if they carry a BRCA mutation, Dr. Pal offers some caveats. First, the findings require confirmation given the limited number of mutation carriers in the study. Second, as a cross-sectional study, it is only a snapshot in time. Third, BRCA testing and the options for risk management are a choice, and many factors enter into the choice, Dr. Pal pointed out.

They include patient preference, cultural factors, information and communication, economic factors, and provider recommendations. “We really need to understand the reasons that these women are making these decisions. Are they being given the opportunity to make an informed decision, or are there other factors that are playing into it where they’re not getting information that they need?” she asked. She said the study highlights the need to design strategies to overcome the reasons for the disparities and to ensure access to testing and cancer risk management practices across all populations.

Session moderator Dr. Patricia Ganz, director of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center of the University of California, Los Angeles, said recruiting from a cancer registry gave the investigators a population-based snapshot of the situation at that time. But the women in the study had their cancer diagnoses between 2009 and 2012, and “a lot of things have happened since then,” she said.

Angelina Jolie was found to have a BRCA mutation and publicly announced her decision to have major risk-reduction surgery. “That led to a lot of public awareness… so,many more women are much more aware,” Dr. Ganz said. “They’re going to ask their doctors about testing if they have a breast cancer diagnosis.”

Also, guidelines have changed, and rather than looking only at family history, clinicians are testing almost any breast cancer patient under age 50 for BRCA. “So I would suggest that perhaps temporal trends may have alleviated some of this disparity,” she said, “and it will be very interesting if Dr. Pal or others recruit a more contemporary sample [and] if we see some shift in this kind of difference in testing and decision making.”

Another factor affecting contemporary BRCA testing is the U.S. Supreme Court’s rejection in 2013 of the patents on the original test, resulting in about a 90% reduction in the cost of the test, making it more affordable for more women. Finally, because a breast cancer diagnosis is devastating to many women, they may choose to pursue breast cancer treatment and risk reduction strategies before addressing their ovarian cancer risk. Therefore, it may be worthwhile to conduct follow up studies to track these women’s cancer risk management choices over time.

The study received funding from the Bankhead Coley Cancer Research Program and the American Cancer Society. Dr. Pal reported no financial disclosures. Patricia Ganz, MD reported stock and other ownership interest in Abbott Laboratories, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Pfizer, and Teva.

Chicago – Young black women with breast cancer are much less likely than white or Hispanic women to undergo testing for BRCA gene mutations, which puts them also at risk for ovarian cancer. And if they carry a BRCA mutation, they are much less likely to undergo removal of their ovaries and fallopian tubes.

Carriers of BRCA mutations have a high lifetime risk of breast and ovarian cancers – up to 60%-70% risk of developing breast cancer, up to 44% risk for ovarian cancer, and a 50% or greater risk for a secondary breast cancer after a first breast cancer diagnosis. Breast cancer risk management may consist of periodic screening or prophylactic mastectomy. But because there are no reliable screening methods for ovarian cancer, the main option for risk management is surgical.At the American Society of Clinical Oncology annual meeting, Dr. Tuya Pal said, “It is very important to think about the benefits of detecting a BRCA mutation. It’s not really about getting them tested, but the health benefit arises from doing something with that information.”

For a population-based, cross-sectional study to investigate women’s receipt of BRCA testing and the uptake of preventive surgery among BRCA mutation carriers, she recruited 440 black, 284 Hispanic, and 897 non-Hispanic white breast cancer survivors through the Florida State Cancer Registry. The study included women who had been diagnosed with invasive breast cancer at up to age 50 years between 2009 and 2012, who completed a baseline survey.

“Among our black women, 36% had received BRCA testing at the time of study recruitment compared with 62% of the Hispanic women and 65% of the non-Hispanic white women,” said Dr. Pal, a clinical geneticist at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla. Even after controlling for meeting high-risk criteria based on national practice guidelines, socioeconomic status variables, and provider referral patterns, there were still significant disparities in BRCA testing (P = .025) for black women, compared with the other two groups.

Of the 1,621 women in the study, 917 (57%) reported BRCA testing, of whom 92 (10%) tested positive for the mutation (28 Black, 13 Hispanic, and 51 non-Hispanic White).

The pattern of ethnic disparity persisted for cancer risk management practices among women with the gene mutation, with 68% of black women opting for bilateral mastectomy vs. 85% of Hispanic women and 94% of non-Hispanic whites. Because mastectomy is not the only form of risk management, Dr. Pal also looked at the rates of breast cancer screening in these women.

“That brought us up to 86% with the black women, 100% among Hispanic women, and 98% among the white women,” she said. However, three out of four of the Black women who did not use any risk management techniques were still in treatment, so it was too early to see what they would do.

For salpingo-oophorectomy, the rates were 32% of black, 85% of Hispanic, and 71% of non-Hispanic white women. After controlling for age at enrollment, time since diagnosis, income, family medical history, and insurance status, there were still disparities between black women and Hispanic women (P = .01) and between black and white women (P = .02).

Even in light of these findings that black women are much less likely to have BRCA testing and to undergo salpingo-oophorectomy if they carry a BRCA mutation, Dr. Pal offers some caveats. First, the findings require confirmation given the limited number of mutation carriers in the study. Second, as a cross-sectional study, it is only a snapshot in time. Third, BRCA testing and the options for risk management are a choice, and many factors enter into the choice, Dr. Pal pointed out.

They include patient preference, cultural factors, information and communication, economic factors, and provider recommendations. “We really need to understand the reasons that these women are making these decisions. Are they being given the opportunity to make an informed decision, or are there other factors that are playing into it where they’re not getting information that they need?” she asked. She said the study highlights the need to design strategies to overcome the reasons for the disparities and to ensure access to testing and cancer risk management practices across all populations.

Session moderator Dr. Patricia Ganz, director of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center of the University of California, Los Angeles, said recruiting from a cancer registry gave the investigators a population-based snapshot of the situation at that time. But the women in the study had their cancer diagnoses between 2009 and 2012, and “a lot of things have happened since then,” she said.

Angelina Jolie was found to have a BRCA mutation and publicly announced her decision to have major risk-reduction surgery. “That led to a lot of public awareness… so,many more women are much more aware,” Dr. Ganz said. “They’re going to ask their doctors about testing if they have a breast cancer diagnosis.”

Also, guidelines have changed, and rather than looking only at family history, clinicians are testing almost any breast cancer patient under age 50 for BRCA. “So I would suggest that perhaps temporal trends may have alleviated some of this disparity,” she said, “and it will be very interesting if Dr. Pal or others recruit a more contemporary sample [and] if we see some shift in this kind of difference in testing and decision making.”

Another factor affecting contemporary BRCA testing is the U.S. Supreme Court’s rejection in 2013 of the patents on the original test, resulting in about a 90% reduction in the cost of the test, making it more affordable for more women. Finally, because a breast cancer diagnosis is devastating to many women, they may choose to pursue breast cancer treatment and risk reduction strategies before addressing their ovarian cancer risk. Therefore, it may be worthwhile to conduct follow up studies to track these women’s cancer risk management choices over time.

The study received funding from the Bankhead Coley Cancer Research Program and the American Cancer Society. Dr. Pal reported no financial disclosures. Patricia Ganz, MD reported stock and other ownership interest in Abbott Laboratories, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Pfizer, and Teva.

Chicago – Young black women with breast cancer are much less likely than white or Hispanic women to undergo testing for BRCA gene mutations, which puts them also at risk for ovarian cancer. And if they carry a BRCA mutation, they are much less likely to undergo removal of their ovaries and fallopian tubes.

Carriers of BRCA mutations have a high lifetime risk of breast and ovarian cancers – up to 60%-70% risk of developing breast cancer, up to 44% risk for ovarian cancer, and a 50% or greater risk for a secondary breast cancer after a first breast cancer diagnosis. Breast cancer risk management may consist of periodic screening or prophylactic mastectomy. But because there are no reliable screening methods for ovarian cancer, the main option for risk management is surgical.At the American Society of Clinical Oncology annual meeting, Dr. Tuya Pal said, “It is very important to think about the benefits of detecting a BRCA mutation. It’s not really about getting them tested, but the health benefit arises from doing something with that information.”

For a population-based, cross-sectional study to investigate women’s receipt of BRCA testing and the uptake of preventive surgery among BRCA mutation carriers, she recruited 440 black, 284 Hispanic, and 897 non-Hispanic white breast cancer survivors through the Florida State Cancer Registry. The study included women who had been diagnosed with invasive breast cancer at up to age 50 years between 2009 and 2012, who completed a baseline survey.

“Among our black women, 36% had received BRCA testing at the time of study recruitment compared with 62% of the Hispanic women and 65% of the non-Hispanic white women,” said Dr. Pal, a clinical geneticist at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla. Even after controlling for meeting high-risk criteria based on national practice guidelines, socioeconomic status variables, and provider referral patterns, there were still significant disparities in BRCA testing (P = .025) for black women, compared with the other two groups.

Of the 1,621 women in the study, 917 (57%) reported BRCA testing, of whom 92 (10%) tested positive for the mutation (28 Black, 13 Hispanic, and 51 non-Hispanic White).

The pattern of ethnic disparity persisted for cancer risk management practices among women with the gene mutation, with 68% of black women opting for bilateral mastectomy vs. 85% of Hispanic women and 94% of non-Hispanic whites. Because mastectomy is not the only form of risk management, Dr. Pal also looked at the rates of breast cancer screening in these women.

“That brought us up to 86% with the black women, 100% among Hispanic women, and 98% among the white women,” she said. However, three out of four of the Black women who did not use any risk management techniques were still in treatment, so it was too early to see what they would do.

For salpingo-oophorectomy, the rates were 32% of black, 85% of Hispanic, and 71% of non-Hispanic white women. After controlling for age at enrollment, time since diagnosis, income, family medical history, and insurance status, there were still disparities between black women and Hispanic women (P = .01) and between black and white women (P = .02).

Even in light of these findings that black women are much less likely to have BRCA testing and to undergo salpingo-oophorectomy if they carry a BRCA mutation, Dr. Pal offers some caveats. First, the findings require confirmation given the limited number of mutation carriers in the study. Second, as a cross-sectional study, it is only a snapshot in time. Third, BRCA testing and the options for risk management are a choice, and many factors enter into the choice, Dr. Pal pointed out.

They include patient preference, cultural factors, information and communication, economic factors, and provider recommendations. “We really need to understand the reasons that these women are making these decisions. Are they being given the opportunity to make an informed decision, or are there other factors that are playing into it where they’re not getting information that they need?” she asked. She said the study highlights the need to design strategies to overcome the reasons for the disparities and to ensure access to testing and cancer risk management practices across all populations.

Session moderator Dr. Patricia Ganz, director of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center of the University of California, Los Angeles, said recruiting from a cancer registry gave the investigators a population-based snapshot of the situation at that time. But the women in the study had their cancer diagnoses between 2009 and 2012, and “a lot of things have happened since then,” she said.

Angelina Jolie was found to have a BRCA mutation and publicly announced her decision to have major risk-reduction surgery. “That led to a lot of public awareness… so,many more women are much more aware,” Dr. Ganz said. “They’re going to ask their doctors about testing if they have a breast cancer diagnosis.”

Also, guidelines have changed, and rather than looking only at family history, clinicians are testing almost any breast cancer patient under age 50 for BRCA. “So I would suggest that perhaps temporal trends may have alleviated some of this disparity,” she said, “and it will be very interesting if Dr. Pal or others recruit a more contemporary sample [and] if we see some shift in this kind of difference in testing and decision making.”

Another factor affecting contemporary BRCA testing is the U.S. Supreme Court’s rejection in 2013 of the patents on the original test, resulting in about a 90% reduction in the cost of the test, making it more affordable for more women. Finally, because a breast cancer diagnosis is devastating to many women, they may choose to pursue breast cancer treatment and risk reduction strategies before addressing their ovarian cancer risk. Therefore, it may be worthwhile to conduct follow up studies to track these women’s cancer risk management choices over time.

The study received funding from the Bankhead Coley Cancer Research Program and the American Cancer Society. Dr. Pal reported no financial disclosures. Patricia Ganz, MD reported stock and other ownership interest in Abbott Laboratories, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Pfizer, and Teva.

CHICAGO – The oral cell cycle inhibitor abemaciclib is active in refractory metastatic breast cancer that is positive for hormone receptors and negative for HER2, according to results of the MONARCH 1 trial.

Nearly a fifth of the 132 women studied experienced a tumor response to this investigational agent on the phase II trial, lead author Dr. Maura N. Dickler of Memorial Sloan Kettering Cancer Center, New York, reported at the annual meeting of the American Society of Clinical Oncology.

“MONARCH 1 confirms single-agent activity of abemaciclib in heavily pretreated patients with hormone receptor–positive, HER2-negative metastatic breast cancer,” she summarized. “The safety and toxicity profile is consistent with previous experience. Twice-daily continuous dosing was feasible, and few patients discontinued treatment due to adverse events.”

“Phase III studies of abemaciclib in combination with endocrine therapies are ongoing,” Dr. Dickler added, referring to MONARCH 2, which is testing the drug in combination with fulvestrant in endocrine-pretreated disease, and MONARCH 3, which is testing the drug in combination with nonsteroidal aromatase inhibitors as initial treatment for metastatic disease.

“This is another piece of evidence that suggests that CDK4 is a very good therapeutic target in breast cancer,” according to session comoderator Dr. Carlos Arteaga, associate director for clinical research and co-leader of the Breast Cancer Research Program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

The toxicity profile of abemaciclib, an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, differs somewhat from that of palbociclib (Ibrance), a similar agent already approved for combination therapy in this setting, he noted in an interview. Specifically, abemaciclib causes somewhat less neutropenia and more diarrhea, possibly because it has less activity against CDK6 (which also plays a role in hematopoiesis) than against CDK4, while palbociclib inhibits the two kinases equally.

The efficacy seen in the trial “is an encouraging result. I think that it begs the question as to whether in patients who are ER positive, maybe the anti-estrogen can be dispensed with by a drug like abemaciclib. The randomized studies that are ongoing of endocrine therapies, plus-minus abemaciclib, will tell us the answer to that I think,” Dr. Arteaga further commented. “And for patients, this represents, in my opinion, progress because it’s just one more drug, one more therapeutic that we can add to the armamentarium. And in the end, patients will win because the drugs will be equally effective with different toxicity profiles, which may allow us to make deliberate recommendations for one versus the other, or to go from one to the other.”

Last year, the Food and Drug Administration awarded abemaciclib Breakthrough Therapy Designation for the treatment of hormone receptor–positive advanced or metastatic breast cancer on the basis of findings from a phase I trial. This designation is designed to expedite the development and review of drugs that are intended to treat a serious condition and for which preliminary clinical evidence indicates a possible substantial improvement over available therapy on a clinically significant endpoint.

Women with metastatic hormone receptor–positive, HER2-negative breast cancer were eligible for MONARCH 1 if they had received at least two chemotherapy regimens (including one containing a taxane) for their disease and had experienced progression on or after endocrine therapy.

Those enrolled were a heavily pretreated population, having received a median of three prior systemic regimens specifically for metastatic disease and five in total, Dr. Dickler reported. All were treated with abemaciclib (LY2835219) 200 mg twice daily on a continuous basis.

Results of the trial showed that the investigator-assessed overall response rate, reflecting patients with partial or complete response, was 19.7%. “This response rate is similar to that of chemotherapy in a taxane-pretreated patient population,” she noted. Findings were similar when responses were instead assessed by blinded reviewers.

The lower bound of the 95% confidence interval, 13.3%, did not exclude the 15% predefined lower bound that had been set in trial planning, Dr. Dickler acknowledged. At the same time, however, the upper bound was 27.5%.

The clinical benefit rate with abemaciclib, adding to the responders the patients who achieved stable disease for at least 6 months, was 42.4%.

The median time to response was 3.7 months, and the median duration of response was 8.6 months. Ultimately, patients had a median progression-free survival of 6.0 months and a median overall survival of 17.7 months.

The most common grade 3 clinical adverse events were diarrhea (seen in 19.7%) and fatigue (12.9%), while none of the patients experienced grade 4 clinical events.

“Generally, the diarrhea was experienced during the first cycle of treatment and resolved quickly,” Dr. Dickler noted. “It was manageable in the majority of patients, responsive to a temporary suspension of study drug, antidiarrheal agents, and dose reductions for grade 3 events. One patient discontinued study therapy due to diarrhea.”

The leading laboratory abnormalities of grade 3 or 4 were a reduction in white blood cell count (27.7%) and a reduction in neutrophil count (26.9%).

The rate of serious adverse events was 24.2%. Three patients died while on therapy or within a month of stopping.

Overall, 49.2% of patients needed a dose reduction, most commonly because of diarrhea, prompting a session attendee to ask whether perhaps a lower starting dose of abemaciclib “would be better tolerated and just as effective.”

The dose used in MONARCH 1 was the maximal tolerated dose established by the phase I trial, Dr. Dickler replied. “Diarrhea obviously was common, but 50% of patients did not require a dose reduction. And when diarrhea did develop, it was really manageable.”

“So I think as a single agent, it’s not unreasonable to start at 200 mg twice daily. In combination with endocrine therapy, in the studies MONARCH 2 and 3, the concurrent dose is 150 mg twice daily,” she pointed out.

The investigators are currently analyzing biomarkers in tumor tissue and plasma to ascertain any predictors of response, according to Dr. Dickler.

Patients with brain metastases were excluded from the trial, she noted. However, “abemaciclib appears to cross the blood-brain barrier, so there is a lot of interest in looking at abemaciclib in patients with brain metastases, and there is a trial that’s ongoing specifically for that.”

Dr. Dickler disclosed that she has a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech/Roche, Merrimack, Novartis, Pfizer, and Syndax, and that she receives research funding (institutional) from Genentech/Roche, Lilly, and Novartis. The trial was sponsored by Eli Lilly and Company.

CHICAGO – The oral cell cycle inhibitor abemaciclib is active in refractory metastatic breast cancer that is positive for hormone receptors and negative for HER2, according to results of the MONARCH 1 trial.

Nearly a fifth of the 132 women studied experienced a tumor response to this investigational agent on the phase II trial, lead author Dr. Maura N. Dickler of Memorial Sloan Kettering Cancer Center, New York, reported at the annual meeting of the American Society of Clinical Oncology.

“MONARCH 1 confirms single-agent activity of abemaciclib in heavily pretreated patients with hormone receptor–positive, HER2-negative metastatic breast cancer,” she summarized. “The safety and toxicity profile is consistent with previous experience. Twice-daily continuous dosing was feasible, and few patients discontinued treatment due to adverse events.”

“Phase III studies of abemaciclib in combination with endocrine therapies are ongoing,” Dr. Dickler added, referring to MONARCH 2, which is testing the drug in combination with fulvestrant in endocrine-pretreated disease, and MONARCH 3, which is testing the drug in combination with nonsteroidal aromatase inhibitors as initial treatment for metastatic disease.

“This is another piece of evidence that suggests that CDK4 is a very good therapeutic target in breast cancer,” according to session comoderator Dr. Carlos Arteaga, associate director for clinical research and co-leader of the Breast Cancer Research Program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

The toxicity profile of abemaciclib, an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, differs somewhat from that of palbociclib (Ibrance), a similar agent already approved for combination therapy in this setting, he noted in an interview. Specifically, abemaciclib causes somewhat less neutropenia and more diarrhea, possibly because it has less activity against CDK6 (which also plays a role in hematopoiesis) than against CDK4, while palbociclib inhibits the two kinases equally.

The efficacy seen in the trial “is an encouraging result. I think that it begs the question as to whether in patients who are ER positive, maybe the anti-estrogen can be dispensed with by a drug like abemaciclib. The randomized studies that are ongoing of endocrine therapies, plus-minus abemaciclib, will tell us the answer to that I think,” Dr. Arteaga further commented. “And for patients, this represents, in my opinion, progress because it’s just one more drug, one more therapeutic that we can add to the armamentarium. And in the end, patients will win because the drugs will be equally effective with different toxicity profiles, which may allow us to make deliberate recommendations for one versus the other, or to go from one to the other.”

Last year, the Food and Drug Administration awarded abemaciclib Breakthrough Therapy Designation for the treatment of hormone receptor–positive advanced or metastatic breast cancer on the basis of findings from a phase I trial. This designation is designed to expedite the development and review of drugs that are intended to treat a serious condition and for which preliminary clinical evidence indicates a possible substantial improvement over available therapy on a clinically significant endpoint.

Women with metastatic hormone receptor–positive, HER2-negative breast cancer were eligible for MONARCH 1 if they had received at least two chemotherapy regimens (including one containing a taxane) for their disease and had experienced progression on or after endocrine therapy.

Those enrolled were a heavily pretreated population, having received a median of three prior systemic regimens specifically for metastatic disease and five in total, Dr. Dickler reported. All were treated with abemaciclib (LY2835219) 200 mg twice daily on a continuous basis.

Results of the trial showed that the investigator-assessed overall response rate, reflecting patients with partial or complete response, was 19.7%. “This response rate is similar to that of chemotherapy in a taxane-pretreated patient population,” she noted. Findings were similar when responses were instead assessed by blinded reviewers.

The lower bound of the 95% confidence interval, 13.3%, did not exclude the 15% predefined lower bound that had been set in trial planning, Dr. Dickler acknowledged. At the same time, however, the upper bound was 27.5%.

The clinical benefit rate with abemaciclib, adding to the responders the patients who achieved stable disease for at least 6 months, was 42.4%.

The median time to response was 3.7 months, and the median duration of response was 8.6 months. Ultimately, patients had a median progression-free survival of 6.0 months and a median overall survival of 17.7 months.

The most common grade 3 clinical adverse events were diarrhea (seen in 19.7%) and fatigue (12.9%), while none of the patients experienced grade 4 clinical events.

“Generally, the diarrhea was experienced during the first cycle of treatment and resolved quickly,” Dr. Dickler noted. “It was manageable in the majority of patients, responsive to a temporary suspension of study drug, antidiarrheal agents, and dose reductions for grade 3 events. One patient discontinued study therapy due to diarrhea.”

The leading laboratory abnormalities of grade 3 or 4 were a reduction in white blood cell count (27.7%) and a reduction in neutrophil count (26.9%).

The rate of serious adverse events was 24.2%. Three patients died while on therapy or within a month of stopping.

Overall, 49.2% of patients needed a dose reduction, most commonly because of diarrhea, prompting a session attendee to ask whether perhaps a lower starting dose of abemaciclib “would be better tolerated and just as effective.”

The dose used in MONARCH 1 was the maximal tolerated dose established by the phase I trial, Dr. Dickler replied. “Diarrhea obviously was common, but 50% of patients did not require a dose reduction. And when diarrhea did develop, it was really manageable.”

“So I think as a single agent, it’s not unreasonable to start at 200 mg twice daily. In combination with endocrine therapy, in the studies MONARCH 2 and 3, the concurrent dose is 150 mg twice daily,” she pointed out.

The investigators are currently analyzing biomarkers in tumor tissue and plasma to ascertain any predictors of response, according to Dr. Dickler.

Patients with brain metastases were excluded from the trial, she noted. However, “abemaciclib appears to cross the blood-brain barrier, so there is a lot of interest in looking at abemaciclib in patients with brain metastases, and there is a trial that’s ongoing specifically for that.”

Dr. Dickler disclosed that she has a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech/Roche, Merrimack, Novartis, Pfizer, and Syndax, and that she receives research funding (institutional) from Genentech/Roche, Lilly, and Novartis. The trial was sponsored by Eli Lilly and Company.

CHICAGO – The oral cell cycle inhibitor abemaciclib is active in refractory metastatic breast cancer that is positive for hormone receptors and negative for HER2, according to results of the MONARCH 1 trial.

Nearly a fifth of the 132 women studied experienced a tumor response to this investigational agent on the phase II trial, lead author Dr. Maura N. Dickler of Memorial Sloan Kettering Cancer Center, New York, reported at the annual meeting of the American Society of Clinical Oncology.

“MONARCH 1 confirms single-agent activity of abemaciclib in heavily pretreated patients with hormone receptor–positive, HER2-negative metastatic breast cancer,” she summarized. “The safety and toxicity profile is consistent with previous experience. Twice-daily continuous dosing was feasible, and few patients discontinued treatment due to adverse events.”

“Phase III studies of abemaciclib in combination with endocrine therapies are ongoing,” Dr. Dickler added, referring to MONARCH 2, which is testing the drug in combination with fulvestrant in endocrine-pretreated disease, and MONARCH 3, which is testing the drug in combination with nonsteroidal aromatase inhibitors as initial treatment for metastatic disease.

“This is another piece of evidence that suggests that CDK4 is a very good therapeutic target in breast cancer,” according to session comoderator Dr. Carlos Arteaga, associate director for clinical research and co-leader of the Breast Cancer Research Program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

The toxicity profile of abemaciclib, an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, differs somewhat from that of palbociclib (Ibrance), a similar agent already approved for combination therapy in this setting, he noted in an interview. Specifically, abemaciclib causes somewhat less neutropenia and more diarrhea, possibly because it has less activity against CDK6 (which also plays a role in hematopoiesis) than against CDK4, while palbociclib inhibits the two kinases equally.

The efficacy seen in the trial “is an encouraging result. I think that it begs the question as to whether in patients who are ER positive, maybe the anti-estrogen can be dispensed with by a drug like abemaciclib. The randomized studies that are ongoing of endocrine therapies, plus-minus abemaciclib, will tell us the answer to that I think,” Dr. Arteaga further commented. “And for patients, this represents, in my opinion, progress because it’s just one more drug, one more therapeutic that we can add to the armamentarium. And in the end, patients will win because the drugs will be equally effective with different toxicity profiles, which may allow us to make deliberate recommendations for one versus the other, or to go from one to the other.”

Last year, the Food and Drug Administration awarded abemaciclib Breakthrough Therapy Designation for the treatment of hormone receptor–positive advanced or metastatic breast cancer on the basis of findings from a phase I trial. This designation is designed to expedite the development and review of drugs that are intended to treat a serious condition and for which preliminary clinical evidence indicates a possible substantial improvement over available therapy on a clinically significant endpoint.

Women with metastatic hormone receptor–positive, HER2-negative breast cancer were eligible for MONARCH 1 if they had received at least two chemotherapy regimens (including one containing a taxane) for their disease and had experienced progression on or after endocrine therapy.

Those enrolled were a heavily pretreated population, having received a median of three prior systemic regimens specifically for metastatic disease and five in total, Dr. Dickler reported. All were treated with abemaciclib (LY2835219) 200 mg twice daily on a continuous basis.

Results of the trial showed that the investigator-assessed overall response rate, reflecting patients with partial or complete response, was 19.7%. “This response rate is similar to that of chemotherapy in a taxane-pretreated patient population,” she noted. Findings were similar when responses were instead assessed by blinded reviewers.

The lower bound of the 95% confidence interval, 13.3%, did not exclude the 15% predefined lower bound that had been set in trial planning, Dr. Dickler acknowledged. At the same time, however, the upper bound was 27.5%.

The clinical benefit rate with abemaciclib, adding to the responders the patients who achieved stable disease for at least 6 months, was 42.4%.

The median time to response was 3.7 months, and the median duration of response was 8.6 months. Ultimately, patients had a median progression-free survival of 6.0 months and a median overall survival of 17.7 months.

The most common grade 3 clinical adverse events were diarrhea (seen in 19.7%) and fatigue (12.9%), while none of the patients experienced grade 4 clinical events.

“Generally, the diarrhea was experienced during the first cycle of treatment and resolved quickly,” Dr. Dickler noted. “It was manageable in the majority of patients, responsive to a temporary suspension of study drug, antidiarrheal agents, and dose reductions for grade 3 events. One patient discontinued study therapy due to diarrhea.”

The leading laboratory abnormalities of grade 3 or 4 were a reduction in white blood cell count (27.7%) and a reduction in neutrophil count (26.9%).

The rate of serious adverse events was 24.2%. Three patients died while on therapy or within a month of stopping.

Overall, 49.2% of patients needed a dose reduction, most commonly because of diarrhea, prompting a session attendee to ask whether perhaps a lower starting dose of abemaciclib “would be better tolerated and just as effective.”

The dose used in MONARCH 1 was the maximal tolerated dose established by the phase I trial, Dr. Dickler replied. “Diarrhea obviously was common, but 50% of patients did not require a dose reduction. And when diarrhea did develop, it was really manageable.”

“So I think as a single agent, it’s not unreasonable to start at 200 mg twice daily. In combination with endocrine therapy, in the studies MONARCH 2 and 3, the concurrent dose is 150 mg twice daily,” she pointed out.

The investigators are currently analyzing biomarkers in tumor tissue and plasma to ascertain any predictors of response, according to Dr. Dickler.

Patients with brain metastases were excluded from the trial, she noted. However, “abemaciclib appears to cross the blood-brain barrier, so there is a lot of interest in looking at abemaciclib in patients with brain metastases, and there is a trial that’s ongoing specifically for that.”

Dr. Dickler disclosed that she has a consulting or advisory role with AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech/Roche, Merrimack, Novartis, Pfizer, and Syndax, and that she receives research funding (institutional) from Genentech/Roche, Lilly, and Novartis. The trial was sponsored by Eli Lilly and Company.

CHICAGO – Dr. Hope Rugo presented results from a phase III trial comparing the safety and efficacy of the trastuzumab biosimilar MYL-1401O and the FDA-approved trastuzumab (Herceptin), indicating the two were comparable. After 24 weeks, the objective response rates were 69.6% (95% CI: 63.62 to 75.51) for MYL-1401O and 64% (95% CI: 57.81 to 70.26) for trastuzumab. Rates of serious adverse events were comparable at 38.1% among patients receiving MYL-1401O and 36.2% among patients receiving Herceptin.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Rugo discusses the regulatory future of the biosimilar and prospects for other cancer drug biosimilars. Dr. Rugo is a professor of medicine at the University of California, San Francisco.

[email protected]

CHICAGO – Dr. Hope Rugo presented results from a phase III trial comparing the safety and efficacy of the trastuzumab biosimilar MYL-1401O and the FDA-approved trastuzumab (Herceptin), indicating the two were comparable. After 24 weeks, the objective response rates were 69.6% (95% CI: 63.62 to 75.51) for MYL-1401O and 64% (95% CI: 57.81 to 70.26) for trastuzumab. Rates of serious adverse events were comparable at 38.1% among patients receiving MYL-1401O and 36.2% among patients receiving Herceptin.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Rugo discusses the regulatory future of the biosimilar and prospects for other cancer drug biosimilars. Dr. Rugo is a professor of medicine at the University of California, San Francisco.

[email protected]

CHICAGO – Dr. Hope Rugo presented results from a phase III trial comparing the safety and efficacy of the trastuzumab biosimilar MYL-1401O and the FDA-approved trastuzumab (Herceptin), indicating the two were comparable. After 24 weeks, the objective response rates were 69.6% (95% CI: 63.62 to 75.51) for MYL-1401O and 64% (95% CI: 57.81 to 70.26) for trastuzumab. Rates of serious adverse events were comparable at 38.1% among patients receiving MYL-1401O and 36.2% among patients receiving Herceptin.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Dr. Rugo discusses the regulatory future of the biosimilar and prospects for other cancer drug biosimilars. Dr. Rugo is a professor of medicine at the University of California, San Francisco.

[email protected]

CHICAGO – The biosimilar trastuzumab antibody MYL-1401O is comparable in safety and efficacy to the FDA-approved trastuzumab (Herceptin) in women with HER2-positive advanced breast cancer, finds a phase III trial reported at the annual meeting of the American Society for Clinical Oncology.

Objective response rates at 24 weeks, the primary endpoint, were 69.6% with MYL-14010 compared to 64% with trastuzumab, reported lead author Dr. Hope Rugo of University of California, San Francisco.

Robert Lodge

A total of 500 patients with metastatic HER2-positive breast cancer were randomized in the Heritage trial to receive taxane chemotherapy with either trastuzumab or MYL-14010 for at least 8 cycles, followed by trastuzumab alone until disease progression. Response rates were assessed at 24 weeks and 458 patients were evaluable. Patients were enrolled at 95 centers in Asia, Latin America, Africa, and Europe.

Safety was comparable between the two arms; 38.1% of patients receiving MYL-1401O and 36.2% of patients receiving trastuzumab experienced at least one serious adverse event. There were four treatment-related deaths in each arm. Neutropenia was the most common adverse event.

“The Heritage study has demonstrated efficacy equivalence between the trastuzumab biosimilar MYL-1401O [and] Herceptin in combinations with taxanes as first-line therapies for HER2-positive metastatic breast cancer at 24 weeks. We also demonstrated similar safety, immunogenicity and pharmokinetics. This proposed biosimilar has the potential to meet the need for an affordable treatment option with HER2-positive breast cancer,” Dr. Rugo said.

She also said that she would readily adopt MYL-1401O as an alternative once it gains FDA approval.

Mylan, makers of MYL-14010, funded the study. Ten investigators reported serving in advisory roles for, having ownership or stock interest in, or receiving financial compensation or honoraria from multiple companies, including Mylan.

[email protected]

On Twitter @JessCraig_OP

CHICAGO – The biosimilar trastuzumab antibody MYL-1401O is comparable in safety and efficacy to the FDA-approved trastuzumab (Herceptin) in women with HER2-positive advanced breast cancer, finds a phase III trial reported at the annual meeting of the American Society for Clinical Oncology.

Objective response rates at 24 weeks, the primary endpoint, were 69.6% with MYL-14010 compared to 64% with trastuzumab, reported lead author Dr. Hope Rugo of University of California, San Francisco.

Robert Lodge

A total of 500 patients with metastatic HER2-positive breast cancer were randomized in the Heritage trial to receive taxane chemotherapy with either trastuzumab or MYL-14010 for at least 8 cycles, followed by trastuzumab alone until disease progression. Response rates were assessed at 24 weeks and 458 patients were evaluable. Patients were enrolled at 95 centers in Asia, Latin America, Africa, and Europe.

Safety was comparable between the two arms; 38.1% of patients receiving MYL-1401O and 36.2% of patients receiving trastuzumab experienced at least one serious adverse event. There were four treatment-related deaths in each arm. Neutropenia was the most common adverse event.

“The Heritage study has demonstrated efficacy equivalence between the trastuzumab biosimilar MYL-1401O [and] Herceptin in combinations with taxanes as first-line therapies for HER2-positive metastatic breast cancer at 24 weeks. We also demonstrated similar safety, immunogenicity and pharmokinetics. This proposed biosimilar has the potential to meet the need for an affordable treatment option with HER2-positive breast cancer,” Dr. Rugo said.

She also said that she would readily adopt MYL-1401O as an alternative once it gains FDA approval.

Mylan, makers of MYL-14010, funded the study. Ten investigators reported serving in advisory roles for, having ownership or stock interest in, or receiving financial compensation or honoraria from multiple companies, including Mylan.

[email protected]

On Twitter @JessCraig_OP

CHICAGO – The biosimilar trastuzumab antibody MYL-1401O is comparable in safety and efficacy to the FDA-approved trastuzumab (Herceptin) in women with HER2-positive advanced breast cancer, finds a phase III trial reported at the annual meeting of the American Society for Clinical Oncology.

Objective response rates at 24 weeks, the primary endpoint, were 69.6% with MYL-14010 compared to 64% with trastuzumab, reported lead author Dr. Hope Rugo of University of California, San Francisco.

Robert Lodge

A total of 500 patients with metastatic HER2-positive breast cancer were randomized in the Heritage trial to receive taxane chemotherapy with either trastuzumab or MYL-14010 for at least 8 cycles, followed by trastuzumab alone until disease progression. Response rates were assessed at 24 weeks and 458 patients were evaluable. Patients were enrolled at 95 centers in Asia, Latin America, Africa, and Europe.

Safety was comparable between the two arms; 38.1% of patients receiving MYL-1401O and 36.2% of patients receiving trastuzumab experienced at least one serious adverse event. There were four treatment-related deaths in each arm. Neutropenia was the most common adverse event.

“The Heritage study has demonstrated efficacy equivalence between the trastuzumab biosimilar MYL-1401O [and] Herceptin in combinations with taxanes as first-line therapies for HER2-positive metastatic breast cancer at 24 weeks. We also demonstrated similar safety, immunogenicity and pharmokinetics. This proposed biosimilar has the potential to meet the need for an affordable treatment option with HER2-positive breast cancer,” Dr. Rugo said.

She also said that she would readily adopt MYL-1401O as an alternative once it gains FDA approval.

Mylan, makers of MYL-14010, funded the study. Ten investigators reported serving in advisory roles for, having ownership or stock interest in, or receiving financial compensation or honoraria from multiple companies, including Mylan.

[email protected]

On Twitter @JessCraig_OP