At the 2022 San Antonio Breast Cancer Symposium, Ruth O’Regan, MD, University of Rochester,  NY, debated the topic “Are All CDK4/6 Inhibitors the Same or Different?” In this debate, she argued that these agents are different.

Dr O’Regan noted the differences in structure and biology, toxicity profiles, and overall survival rates associated with the agents. She also discussed various treatment scenarios that help to illustrate these differences.

Transcript

Hi. I'm Ruth O'Regan. I'm professor of medicine at the University of Rochester. I'm here at the San Antonio Breast Cancer Symposium and I wanted to mention a debate I was involved in if you haven't seen it. Myself and Dr Debra Pratt from Texas Oncology debated whether CDK4/6 inhibitors are the same or different. I was very fortunate because I had the “They’re Different” side, which I think they clearly are.

We basically pointed out that there were differences in the structure of these agents, and also in their biology as far as how well they target CDK4 and CDK6. The top toxicity profile between these agents is clearly different in that ribociclib and palbociclib tend to cause more neutropenia, versus abemaciclib, which tends to cause less neutropenia but more diarrhea.

Looking at outcome, one of the striking things about the first-line studies with these agents is that the hazard ratio for progression-free survival is incredibly similar across all these trials. But the strange thing is that we're seeing differences in overall survival, so all the MONALEESA first-line trials that incorporated ribociclib show a significant improvement in overall survival versus the other 2 agents. The MONARCH trial did show an improvement in overall survival, but it's not statistically significant yet. In the first-line trial, palbociclib really showed a modest improvement in overall survival. We don't know why that is. It could be differences between the trials, or it could be that the agents are somewhat different as well.

We then looked at several different scenarios where there's pretty high-level data for using one CDK4/6 inhibitor over another. For example, ribociclib now has 2 trials in the premenopausal setting, including a trial presented at this meeting, where they looked at premenopausal patients with high volume disease, where they showed that ribociclib with endocrine therapy is superior to doublet chemotherapy. We also talked about brain metastasis. There was a phase 2 trial of abemaciclib in patients with brain metastasis, whereas there isn't with the other agents.

Last, we talked about what to do when patients experience progressions on CDK4/6 inhibitors. Does it make sense to use another CDK4/6 inhibitor or continue the CDK4/6 inhibitor? What we know from the MAINTAIN study is that if you have had disease progression on a CDK4/6 inhibitor, for example, palbociclib, patients can benefit from switching to a different CDK inhibitor, in that case, ribociclib, and changing endocrine therapy.

Also presented at this meeting and with the PACE study, in which most patients who had received palbociclib in the first-line setting continued on palbociclib and switched the endocrine therapy, and that actually was not affected. There was no difference in progression-free survival on that study. Although, I will say the trials are kind of apples and oranges because in one they switched the CDK inhibitor and the other they didn't.

So, my point of the debate was that they were different, and I think I clearly proved that. Thank you.

Source:

O’Regan RJ. “Are All CDK4/6 Inhibitors the Same or Different? - CON” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas.