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Emerging Role of Abemaciclib for HR+ Advanced Breast Cancer

Panelists: Adam M. Brufsky, MD, PhD, University of Pittsburgh School of Medicine; Mark E. Robson, MD, Memorial Sloan Kettering Cancer Center; Aditya Bardia, MD, MPH, Massachusetts General Hospital Cancer Center; Kimberly L. Blackwell, MD, Duke Cancer Institute
Published Online: Friday, Mar 03, 2017



Transcript:

Adam M. Brufsky, MD, PhD:
There’s a third one we haven’t talked about: abemaciclib. Do people have experience with abemaciclib? Mark, you have experience with it?

Mark E. Robson, MD: We have a trial, but it doesn’t seem, again, to be particularly different to us.

Adam M. Brufsky, MD, PhD: Aditya, what do you think?

Aditya Bardia, MD, MPH: It’s another CDK4/6 inhibitor by a different company. The only difference we’ve seen is that the side effect profile is slightly different, which probably relates to the fact that it affects the CDK6 more than the CDK4. So, diarrhea is the most common side effect that’s seen with abemaciclib. The incidence of neutropenia is less, which could be a good thing, but some have also questioned if it is really hitting the target hard because neutropenia is an on-target effect of CDK4/6, so you should be seeing neutropenia if you are hitting CDK4/6. The other difference is that abemaciclib is given on a continuous basis while palbociclib is given 3 weeks on, 1 week off. But whether that’s important, whether that would result in a clinically meaningful benefit, we don’t know at this time.

Adam M. Brufsky, MD, PhD: Kim?

Kimberly L. Blackwell, MD: I walked away from the San Antonio Breast Cancer Symposium more excited about this drug than I had been at ASCO. At ASCO, we had the single agent trial—one differentiator of abemaciclib versus the 2 other CDK inhibitors. At least there’s some described activity in phase I/II studies by itself, not layered on top of endocrine therapy. So, that’s exciting when you see single-agent activity that, at least to my knowledge, we really haven’t seen with the other CDK inhibitors. But the trial was powered on an overall response rate. It was supposed to outperform single-agent capecitabine in a similar patient population. It wasn’t a randomized study and it didn’t meet its primary endpoint, although there were some prolonged responders in the single agent trial. But I’ve got a renewed enthusiasm about the drug because Sara Hurvitz presented neoMONARCH, which is a preoperative study, that looked at endocrine therapy I think for 2 weeks with a Ki-67 endpoint; abemaciclib alone or the combination of the 2. Abemaciclib by itself and abemaciclib plus endocrine therapy resulted in greater than 90% reduction in Ki-67. To me, that actually was quite exciting. We saw such a significant reduction in Ki-67 in the preoperative setting with single-agent abemaciclib. It was actually as good as preoperative anti-estrogen therapy. I’ve gotten a more renewed enthusiasm from the results of that preoperative neoMONARCH study for this drug.

Adam M. Brufsky, MD, PhD: Right, and we have 2 large trials, that I guess we’re waiting to see the results of, that are very similar to MONALEESA and to PALOMA.

Kimberly L. Blackwell, MD: Yes, but we all want that single-agent drug. The good news about advanced ER-positive breast cancer is we’re seeing a lot of long responders. In my practice, you get a CDK inhibitor first-line. You either get fulvestrant, if you haven’t had it, or you get everolimus. And then, that switch to chemotherapy, it’s pretty harsh for me as the doctor. So, I’m hoping that we do get this drug in that space as a single agent.

Transcript Edited for Clarity

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Transcript:

Adam M. Brufsky, MD, PhD:
There’s a third one we haven’t talked about: abemaciclib. Do people have experience with abemaciclib? Mark, you have experience with it?

Mark E. Robson, MD: We have a trial, but it doesn’t seem, again, to be particularly different to us.

Adam M. Brufsky, MD, PhD: Aditya, what do you think?

Aditya Bardia, MD, MPH: It’s another CDK4/6 inhibitor by a different company. The only difference we’ve seen is that the side effect profile is slightly different, which probably relates to the fact that it affects the CDK6 more than the CDK4. So, diarrhea is the most common side effect that’s seen with abemaciclib. The incidence of neutropenia is less, which could be a good thing, but some have also questioned if it is really hitting the target hard because neutropenia is an on-target effect of CDK4/6, so you should be seeing neutropenia if you are hitting CDK4/6. The other difference is that abemaciclib is given on a continuous basis while palbociclib is given 3 weeks on, 1 week off. But whether that’s important, whether that would result in a clinically meaningful benefit, we don’t know at this time.

Adam M. Brufsky, MD, PhD: Kim?

Kimberly L. Blackwell, MD: I walked away from the San Antonio Breast Cancer Symposium more excited about this drug than I had been at ASCO. At ASCO, we had the single agent trial—one differentiator of abemaciclib versus the 2 other CDK inhibitors. At least there’s some described activity in phase I/II studies by itself, not layered on top of endocrine therapy. So, that’s exciting when you see single-agent activity that, at least to my knowledge, we really haven’t seen with the other CDK inhibitors. But the trial was powered on an overall response rate. It was supposed to outperform single-agent capecitabine in a similar patient population. It wasn’t a randomized study and it didn’t meet its primary endpoint, although there were some prolonged responders in the single agent trial. But I’ve got a renewed enthusiasm about the drug because Sara Hurvitz presented neoMONARCH, which is a preoperative study, that looked at endocrine therapy I think for 2 weeks with a Ki-67 endpoint; abemaciclib alone or the combination of the 2. Abemaciclib by itself and abemaciclib plus endocrine therapy resulted in greater than 90% reduction in Ki-67. To me, that actually was quite exciting. We saw such a significant reduction in Ki-67 in the preoperative setting with single-agent abemaciclib. It was actually as good as preoperative anti-estrogen therapy. I’ve gotten a more renewed enthusiasm from the results of that preoperative neoMONARCH study for this drug.

Adam M. Brufsky, MD, PhD: Right, and we have 2 large trials, that I guess we’re waiting to see the results of, that are very similar to MONALEESA and to PALOMA.

Kimberly L. Blackwell, MD: Yes, but we all want that single-agent drug. The good news about advanced ER-positive breast cancer is we’re seeing a lot of long responders. In my practice, you get a CDK inhibitor first-line. You either get fulvestrant, if you haven’t had it, or you get everolimus. And then, that switch to chemotherapy, it’s pretty harsh for me as the doctor. So, I’m hoping that we do get this drug in that space as a single agent.

Transcript Edited for Clarity
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Leveraging New Evidence in the Context of Evolving Early-Stage Treatment Standards in HER2-Positive Breast CancerJan 30, 20181.5
14th Annual School of Breast Oncology® OnlineFeb 10, 201825
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