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Questioning CDK4/6 Inhibitor Cross-Resistance in HR+ mBC

Panelists: Joyce O Shaughnessy, MD, Baylor-Sammons Cancer Center; Aditya Bardia, MD, MPH, Massachusetts General Hospital; Adan M. Brufsky, MD, PhD, Comprehensive Breast Cancer Center; Heather L. McArthur, MD, MPH, Cedars-Sinai Medical Center; Ruth O Regan, MD, University of Wisconsin Carbone Cancer Center; Tiffany A. Traina, MD, Memorial Sloan Kettering Cancer Center
Published: Wednesday, Jan 30, 2019



Transcript: 

Joyce O’Shaughnessy, MD:
Now, Aditya, you’ve been very interested in whether there’s any non–cross-resistance between these 2 and have been collecting a case series. Can you say a little bit about that?

Aditya Bardia, MD, MPH: So, essentially, as was being discussed earlier, it appeared that palbociclib and ribociclib are very similar, and abemaciclib is competitively slightly different from ribociclib and palbociclib. And, if we look at the approval abemaciclib, it’s also approved as monotherapy. But what we don’t know is if you have a patient who’s progressed on AI [aromatase inhibitor] plus palbociclib or Faslodex plus ribociclib, can you use abemaciclib as monotherapy in that setting? So we just looked at our experience, along with your experience in [the] US Oncology [Network], to see what’s the response rate in patients who have received prior CDK4/6 inhibitor with palbociclib or ribociclib and then received abemaciclib. And what we see is that there’s a small subset of patients who continue to derive benefit with abemaciclib, even if they’ve had disease progression on prior palbociclib or ribociclib. But, for the large subset, they just have disease progression. And the way we defined that was if they have disease progression in 60 to 90 days, which clinically is not that meaningful. What we don’t know at this time is: Can we identify biomarkers to predict that this is a patient who should be continued on CDK4/6 blockade versus a patient who should be triaged to some other therapy?

Adam M. Brufsky, MD, PhD: I think we talked about that a few weeks ago, actually. I’d love to get involved. I’d love to get involved because we can pool our data together. Seriously, I have a couple [of] patients just like that. I don’t know how many you have. How many do you have in your case series, by the way?

Aditya Bardia, MD, MPH: So counting the 1 from Joyce, it’s 40 patients.

Adam M. Brufsky, MD, PhD: We probably have about 10.

Aditya Bardia, MD, MPH: If we all pool together, we’re probably close to 100.

Ruth O’Regan, MD: I would think that Lilly is probably capturing these data, right? Because with single agent usage of abemaciclib…

Tiffany A. Traina, MD: But potentially not post exposure.

Ruth O’Regan, MD: I guess they could look, because I’m sure it is being done. It could certainly be done in the community setting.

Tiffany A. Traina, MD: Right.

Joyce O’Shaughnessy, MD: What I have found is that in the patients I had who went for 6 months or longer and had some clinical benefit, there had been some time that had gone by [in] between. I’ve actually never given abemaciclib immediately after progression on palbociclib or ribociclib. But if some time had gone by, then I had actually had some patients who did better, even a few who had marked liver metastasis improvement, very quite like the MONARCH 1 population who hadn’t particularly benefitted from palbociclib or ribociclib up front. And then, for whatever reason, they did benefit. So I have seen some [of] that, and you have, too. Has it been with some period of time gone by?

Aditya Bardia, MD, MPH: That’s a good question. We’ve not specifically looked at that point, but one could make a case that if you give a CDK4/6 break, it would resensitize the cells to CDK4/6 inhibition again.

Joyce O’Shaughnessy, MD: Yes.

Heather L. McArthur, MD, MPH: Are you getting serial biopsies with those patients? Because that would be incredibly powerful.

Joyce O’Shaughnessy, MD: Aditya wanted us to send in all of our ctDNA [circulating tumor DNA] data, as well, too. Aditya, you had even seen some benefit. We both have with abemaciclib, even with RB mutations. In fact, The [University of Texas] MD Anderson [Cancer Center] group, that was another thing. They said they had RB-deficient lines and still benefited when inhibited by abemaciclib.

Adam M. Brufsky, MD, PhD: That’s a little weird. We have to figure out why that would be.

Transcript edited for clarity.

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Transcript: 

Joyce O’Shaughnessy, MD:
Now, Aditya, you’ve been very interested in whether there’s any non–cross-resistance between these 2 and have been collecting a case series. Can you say a little bit about that?

Aditya Bardia, MD, MPH: So, essentially, as was being discussed earlier, it appeared that palbociclib and ribociclib are very similar, and abemaciclib is competitively slightly different from ribociclib and palbociclib. And, if we look at the approval abemaciclib, it’s also approved as monotherapy. But what we don’t know is if you have a patient who’s progressed on AI [aromatase inhibitor] plus palbociclib or Faslodex plus ribociclib, can you use abemaciclib as monotherapy in that setting? So we just looked at our experience, along with your experience in [the] US Oncology [Network], to see what’s the response rate in patients who have received prior CDK4/6 inhibitor with palbociclib or ribociclib and then received abemaciclib. And what we see is that there’s a small subset of patients who continue to derive benefit with abemaciclib, even if they’ve had disease progression on prior palbociclib or ribociclib. But, for the large subset, they just have disease progression. And the way we defined that was if they have disease progression in 60 to 90 days, which clinically is not that meaningful. What we don’t know at this time is: Can we identify biomarkers to predict that this is a patient who should be continued on CDK4/6 blockade versus a patient who should be triaged to some other therapy?

Adam M. Brufsky, MD, PhD: I think we talked about that a few weeks ago, actually. I’d love to get involved. I’d love to get involved because we can pool our data together. Seriously, I have a couple [of] patients just like that. I don’t know how many you have. How many do you have in your case series, by the way?

Aditya Bardia, MD, MPH: So counting the 1 from Joyce, it’s 40 patients.

Adam M. Brufsky, MD, PhD: We probably have about 10.

Aditya Bardia, MD, MPH: If we all pool together, we’re probably close to 100.

Ruth O’Regan, MD: I would think that Lilly is probably capturing these data, right? Because with single agent usage of abemaciclib…

Tiffany A. Traina, MD: But potentially not post exposure.

Ruth O’Regan, MD: I guess they could look, because I’m sure it is being done. It could certainly be done in the community setting.

Tiffany A. Traina, MD: Right.

Joyce O’Shaughnessy, MD: What I have found is that in the patients I had who went for 6 months or longer and had some clinical benefit, there had been some time that had gone by [in] between. I’ve actually never given abemaciclib immediately after progression on palbociclib or ribociclib. But if some time had gone by, then I had actually had some patients who did better, even a few who had marked liver metastasis improvement, very quite like the MONARCH 1 population who hadn’t particularly benefitted from palbociclib or ribociclib up front. And then, for whatever reason, they did benefit. So I have seen some [of] that, and you have, too. Has it been with some period of time gone by?

Aditya Bardia, MD, MPH: That’s a good question. We’ve not specifically looked at that point, but one could make a case that if you give a CDK4/6 break, it would resensitize the cells to CDK4/6 inhibition again.

Joyce O’Shaughnessy, MD: Yes.

Heather L. McArthur, MD, MPH: Are you getting serial biopsies with those patients? Because that would be incredibly powerful.

Joyce O’Shaughnessy, MD: Aditya wanted us to send in all of our ctDNA [circulating tumor DNA] data, as well, too. Aditya, you had even seen some benefit. We both have with abemaciclib, even with RB mutations. In fact, The [University of Texas] MD Anderson [Cancer Center] group, that was another thing. They said they had RB-deficient lines and still benefited when inhibited by abemaciclib.

Adam M. Brufsky, MD, PhD: That’s a little weird. We have to figure out why that would be.

Transcript edited for clarity.
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