Breast Cancer Update, Issue 2, 2016 (Video Program) - Video 20Perspective on CDK4/6 inhibitors in HR-positive mBC
4:52 minutes.
TRANSCRIPTION:
DR SLEDGE: We have, I would say, compelling data with the first of these, palbociclib, both in combination with aromatase inhibitor therapy and in combination with fulvestrant that one sees significant — and not just statistically significant, but I would argue clinically significant — improvements in terms of progression-free survival with relatively modest — not zero, but relatively modest and manageable toxicity. That toxicity is largely — not completely, but largely — in the form of neutropenia that requires one to monitor CBCs, a little bit of a pain in the neck compared to just giving someone an aromatase inhibitor and sending them away for 3 months, but not a horrible burden. There’s lots of things that we don’t know yet. First, of course, 2 of the 3 CDK4/6 inhibitors we don’t yet have Phase III data for, so we’ll have to wait and see whether or not there are any significant differences or advantages or disadvantages for one versus the other. Secondly, while we have very impressive results in terms of progression-free survival, so, for instance, the PALOMA-2 trial, which is the larger Phase III trial of AI plus-minus CDK4/6 inhibition, is showing about a 10-month improvement in terms of progression-free survival, very impressive data. Is that going to translate to an improvement in overall survival, which, of course, is a crucial question? All of us remember — I certainly remember having devoted a decade of my life to it, that in the metastatic setting with anti-VEGF therapy we got a fairly dramatic — not quite as, but fairly dramatic — improvement in terms of progression-free survival that did not translate to an improvement in overall survival. So I think we have to be at least a little modest until we get those first data sets in. DR LOVE: What about the data on using it alone? And again, I don’t think that we saw much in the way of monotherapy benefit with palbociclib, but there was benefit — it looked like people responded with abemaciclib. DR SLEDGE: Yes, it’s real. I guess first from a conflict of interest standpoint, I’m one of the people running a Phase III trial with abemaciclib. I’m the PI on it. So you can take that as a qualifier. But certainly the data that was presented with abemaciclib in a Phase II setting clearly shows an objective response rate in the absence of hormonal therapy. That’s pretty exciting and pretty interesting and, of course, leads to the question as to where do we see these benefits? How much of the benefit is coming from estrogen blockade, and how much of the benefit is coming, if you will, from almost more of a classic chemotherapeutic effect and on cell division? DR LOVE: So usually when I ask people, “Can you describe a situation where you’re going to use first-line therapy for metastatic ER-positive, HER2-negative disease where you’re not going to add in palbociclib,” people take a long breath and think about it for a while. Can you describe a case where you don’t use it? DR SLEDGE: I actually encourage patients to use it. I actually find the palbo data quite impressive. And I think going 2 years without progression in the metastatic setting for the average patient is basically a good thing. So it’s certainly something I encourage. Now, I will say as a qualifier that I still have concerns about this, because all of us who treat breast cancer regularly have patients who went on tamoxifen or an AI and remained progression free for a decade. And anecdotes are dangerous, so I’ll share one. I have a patient who developed metastatic breast cancer to her lung, biopsy proven, in 1992 and was then on 2 hormonal therapies, first tamoxifen and then an AI over the next 20 years. DR LOVE: Wow! DR SLEDGE: And all of us have cases like this. If that patient had gone on a CDK4/6 inhibitor, she still probably would have responded for 20 years, I would imagine, but would have had more toxicity and hugely more expense. So I think one of the things that I would love to see would be some data that would actually point us in the direction of are there patients who get specific benefit from the addition of a CDK4/6 inhibitor? |