CDK4/6 Inhibitors for Triple-Positive Breast Cancer



Adam Brufsky, MD, PhD: Let’s start with I-O [immune-oncology]. Do you think I-O is going to add anything to HER2-positive disease or not? Who wants to take that one? I see Mark smiling. I’ll give it to you first and then everybody else can go.

Mark D. Pegram, MD: I don’t know the answer but we’ll find out because the CLEOPATRA plus or minus atezolizumab trial is underway, and we’ll get a definitive answer, hopefully. I’m going to stay on the sidelines on this one. I don’t think it’s a guarantee. I bet you that there is a subset of HER2-positive patients who probably do derive a benefit, but I bet there are others who probably don’t, and so in an unselected population who knows? PD-L1, is that going to be the same in the HER2-positive case as it was in triple negative? I don’t know.

Virginia Kaklamani, MD:I have a patient, we had a phase 2 trial with atezolizumab, HP [trastuzumab, pertuzumab] plus chemotherapy, and this young patient who just had a baby, came in with metastatic disease, bone mostly, so ER [estrogen receptor]-positive, as well, and we put her on the trial. She was on it for a while and, of course, stopped chemotherapy, progressed, restarted chemotherapy, and now she’s, again, off of chemotherapy on atezolizumab/trastuzumab/pertuzumab for—this is her 41st cycle. She stayed pretty much no disease in the breast because she was de novo metastatic, just some bone lesions. We have not put her on endocrine therapy. She’s just cruising along. I’ve started chemotherapy once, twice, on her, and now off chemotherapy. Now, is this the atezolizumab effect? Is she really lucky? I don’t know. The data, so far, are not as impressive as the triple-negative data, which weren’t that impressive to begin with, initially.

Adam Brufsky, MD, PhD: I agree. Before we go on to the very fascinating question of the treatment of triple-positive disease, does anybody have any more comments about I-O and where they think this is going? Didn’t K2 not do too well? Was that the trial I’m thinking of? It was I-O plus something, some regimen second line and beyond in HER2.

Mark D. Pegram, MD: There was a T-DM1 [trastuzumab emtansine]/atezolizumab trial that halted due to futility, actually.

Adam Brufsky, MD, PhD: That’s the one I was thinking of. That was K2.

Carey K. Anders, MD: We had the PANACEA trial a couple of years ago at the San Antonio Breast Cancer Symposium. Sherene Loi, MBBS, PhD, presented. It was trastuzumab/pembrolizumab and associated with TILs [tumor-infiltrating lymphocytes]?

Adam Brufsky, MD, PhD: Yes, you can always use TILs, right?

Carey K. Anders, MD: I’m curious if Virginia has sequenced the tumor for her patient who’s on cycle 41?

Virginia Kaklamani, MD:I have not, yet. I’m planning on doing all that around the time that she progresses so I can figure out what to do.

Adam Brufsky, MD, PhD: Yes, what to do next.

Mark D. Pegram, MD: The sad thing about the anecdotes is I have multiple similar anecdotes back in the single-agent trastuzumab days.

Adam Brufsky, MD, PhD: We can learn something from them if we do biomarkers and genomics, we’ll learn something from all the single anecdotes.

Rashmi K. Murthy, MD, MBE: Going back to the PANACEA trial, that had a very modest response rate, only 15%, but I think of those patients who did have a response, their duration of response was quite prolonged, and this was a heavily pretreated patient population. I’m keeping my fingers crossed for the NRG atezolizumab study, though, but we’ll see.

Adam Brufsky, MD, PhD: I’ve heard that doesn’t have a lot, accrual is poor on that. The scuttlebutt is it is not accruing very well so. We’ve had a hard time getting people on it.

Mark D. Pegram, MD: Surprising.

Rashmi K. Murthy, MD, MBE: Yes, I referred a young patient to that trial before. We had it open at a different site, and I did hear back from her. She had a fantastic, near complete response, in a patient who had liver disease. I’m hopeful that immunotherapy is going to have a role, but I think we’ll have to see.

Adam Brufsky, MD, PhD: Let’s go to the next one, what about CDK4/6 [cyclin-dependent kinases 4 and 6 inhibitors]? Any comments on CDK4/6 with anti-HER2? Carey, what do you think?

Carey K. Anders, MD: We have the PATINA study open, which is the transition from taxane/HP at the time that you’re transitioning to antibody therapy alone, with endocrine therapy for the hormone receptor-positive patients to have a randomization to palbociclib, yes or no. It’s very interesting, like Mark said, we’ll have to sit on the sidelines to see what happens, but I’ve certainly been recommending it for my patients who have triple-positive breast cancer. It’d be wonderful to see that we could push the PFS [progression-free survival] even farther than the 18-month median with the addition of the CDK4/6 inhibitor.

I do worry because I have seen where this has been done without trial work, and I particularly would caution against adding abemaciclib, at this point, until we have safety data, due to the concurrent adverse effect profile of GI [gastrointestinal] toxicity and diarrhea with our abemaciclib compound and the HP.

Adam Brufsky, MD, PhD: We’re doing that, anyway, because we have someone who is triple-positive and you can decide whether to go the HER2 route or the ER route, and we’ve gone the HER2 route. As Mark has told us, there’s enough trastuzumab on board for a couple of months once you stop it. You are doing the combo anyway by putting them on abemaciclib. You’re doing it anyway. It’s interesting where that’s going to go.

Virginia Kaklamani, MD:I think the monarcHER data are relatively interesting, and I think that approach is great. The issue is going to be that we have all of these options in these triple-positive patient populations, so what do we do? Do we continue triple therapy? Do we stop something? Do we continue something else? I don’t know that we’re ever going to know.

Adam Brufsky, MD, PhD: No one knows. It is all going to be clinical judgment.

Transcript Edited for Clarity

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