Comparison of CDK4/6 Therapies for HR+/HER2- MBC

EP: 1.Identifying PIK3CA Mutations in HR+ HER2- MBC

EP: 2.HR+ MBC: Prognostic Factors and Treatment Planning

EP: 3.Frontline Treatment Approaches for HR+/HER2- MBC

EP: 4.HR+/HER2- MBC: Updated OS Data From MONALEESA-2

EP: 5.Ribociclib + ET for HR+/HER2- MBC: QoL and OS Data

EP: 6.MONALEESA Data in HR+/HER2- MBC: Sequencing Therapy

EP: 7.HR+/HER2- MBC: CDK4/6 Inhibitors + ET as Frontline Therapy

EP: 8.HR+/HER2- MBC: CKD4/6 Inhibitor Treatment Toxicities

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EP: 9.Comparison of CDK4/6 Therapies for HR+/HER2- MBC

EP: 10.CDK4/6 Treatment Selection for HR+/HER2- MBC

EP: 11.Targeting the PI3K Pathway in HR+/HER2- MBC

EP: 12.PI3K Inhibitors for PIK3CA-Mutated HR+ MBC

EP: 13.Managing Patients With HR+ MBC on PI3K Therapy

EP: 14.PI3K Therapy for HR+/HER2- MBC: Metabolic Syndrome

EP: 15.Sequencing Therapy in HR+/HER2- MBC

EP: 16.Novel Agents Under Study for HR+/HER2- MBC

EP: 17.Treatment Advances in HR+/HER2- MBC

Joyce O’Shaughnessy, MD: To finish up this section on CDK4/6 inhibitors, it’s a challenging question, are these agents all the same? Are there certain patient populations for which you’d be more inclined to recommend one over the other? I find that this is a bit of an evolving area because we get new data that are coming out on a regular basis. It’s helpful to think about the primary end points but also some of the subsets of patients that we have. Neil, how do you think about the 3 of these, are they interchangeable? How do you approach them in your practice?

Neil M. Iyengar, MD: I agree with what you said that this is an evolving area, because as we get longer-term follow-up, as we understand the mechanisms better, we are starting to pick up on some differences, I would say. I would start by saying that the mechanism of action is very similar if not the same among the agents, but I think that there may be differences in stimulating that mechanism of action, or the degree to which that mechanism of action is stimulated. I think that we have certainly seen in preclinical models and in some biomarker studies that the potency of targeting CDK4 vs CDK6 and the bioavailability is different among these 3 agents. Whether or not that’s clinically relevant, I think that’s the area that is evolving. That’s where we’re going to start to see with longer-term follow-up, and we’re already starting to see with longer-term follow-up, some differences in end points like overall survival, which of course is clearly clinically significant.

The short answer to your question, Joyce, is that, yes, these are different. To what degree are these differences clinically significant? I think we have yet to see that, although we’re starting to see. To address your final question, I do think that there are specific patient predictors or factors that do help in the selection of which one of these agents we would use. For example, in premenopausal women, I would certainly use ribociclib because you have a clinical trial that is a priori designed for this population rather than a subgroup analysis. Then when we start to think about toxicity, which we’ve all just discussed, I think that can also help guide our treatment. Perhaps if we’re a little worried about myelosuppression in a particular patient, or if we have a patient who has baseline IBS [irritable bowel syndrome] or GI [gastrointestinal] issues, that may have us avoid abemaciclib, for example. I think that there are some clinically significant differences here.

Transcript edited for clarity.