HR+/HER2- Metastatic Breast Cancer: Selecting From Approved CDK4/6 Inhibitors


Richard Finn, MD, considers data behind all three approved CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer and how they compare.


Richard Finn, MD: With all 3 CDK4/6 inhibitors being approved in the relatively same indications, obviously there’s an interest in comparing these agents. When we look at the primary end points of these studies, these agents all have performed very similarly. All have very similar hazard ratios for decreasing the risk of progression. All have very similar objective response rates and all of them tend to be well tolerated. Though, as we commented, there are some adverse effect differences between the drugs, but there are also some consistencies such as leukopenia and neutropenia. Both ribociclib and palbociclib are dosed 3 weeks on and 1 week off and abemaciclib is dosed continuously. With that being said, as I commented, the primary end points are all very similar.

Most secondary end points behave very similarly, but when we look at some of the overall survival data that’s been coming out, we do see significant improvements in overall survival with ribociclib in combination with an AI [aromatase inhibitor] and fulvestrant and abemaciclib, similarly showed an improvement in overall survival [OS] in combination with fulvestrant. We are still waiting for the frontline OS data with palbociclib and abemaciclib. One thing to keep in mind is while all these studies did look at ER-positive HER2-negative breast cancer, they did differ a little bit in the populations they accrued. The PALOMA-3 study [NCT01942135], which showed a numerical difference in OS, but was not statistically significant, did allow patients to have prior chemotherapy prior to coming to the study, which the other CDK inhibitor studies did not.

We see that when we look at the control arms in these studies, they do behave a little differently with the PALOMA-3 control arm having the shortest PFS [progression-free survival], whereas ribociclib and abemaciclib studies in the AI pretreated population tend to do better. That’s because of the baseline characteristics and inclusion criteria. Now, when we look at the frontline studies as mentioned, we’re still waiting. We will see at ASCO [2022 American Society of Clinical Oncology Annual Meeting] the overall survival data from PALOMA-2 [NCT01740427], and then hopefully in the future, we will see data with abemaciclib overall survival data in combination with AIs in the frontline setting. Again, it’s important to consider that the inclusion criteria were somewhat different and the populations they accrued were a little different. Specifically, in the frontline studies, the number of patients who had a disease-free interval of less than 1 year was about 20% of the patients in PALOMA-2; however, in the ribociclib and abemaciclib studies, that was really a single-digit number. How all this will impact secondary outcomes is yet to be seen. However, I think the take-home message is CDK inhibitors have changed the natural history of ER-positive breast cancer. I think all of us at UCLA are very proud of the role he played in bringing these drugs to the clinic, and there is more to figure out in the years to come.

Transcript edited for clarity.

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