Potential for CDK4/6 Inhibitors in Metastatic CRPC


Expert panelists briefly reflect on clinical trial data with CDK4/6 inhibitors in metastatic castration-resistant prostate cancer and how their role in this setting might evolve.


Rana McKay, MD:As we think about other targeted therapies, there are other drugs, like CDK4/6 inhibitors. They have made tremendous headway in breast cancer, are approved as monotherapy in the refractory setting, and are approved in combination with hormonal therapy in the earlier metastatic setting. Abemaciclib is even approved in the localized early setting. There are several CDK4/6 inhibitors that have been evaluated in prostate cancer. We’ve got data from ribociclib. We’ve got data emerging about abemaciclib. What are your thoughts about CDK4/6 inhibition?

Ulka Vaishampayan MD:I don’t think it’s proven yet. It’s in the investigational phase, and the toxicities aren’t trivial. In patients with prostate cancer, it’s not an easy medication to administer, especially over months and months.

Arash Rezazadeh Kalebasty, MD:… hasn’t been even close to what we see in breast cancer.

Ulka Vaishampayan MD:Nothing like the breast.

Arash Rezazadeh Kalebasty, MD:It’s very low. For the toxicity, maybe there’s a combination we have to use. I remember the days that we had NGS [next-generation sequencing]. Everybody was getting excited, “Let’s use a drug off-label. It’s going to work.” But it’s totally different from cancer to cancer.

Rana McKay, MD:It hasn’t panned out. We haven’t seen a lot of data presented in this space. We’ve seen the CYCLONE 1 data in a very refractory disease setting with a response rate of less than 10%. But if we think about these agents, pairing them with AR pathway inhibitors, utilization in the end-state setting where that disease isn’t necessarily be hormonally driven, may not bethe best strategy. CYCLONE 2 looks at the combination in the frontline CRPC [castration-resistant prostate cancer] setting; that trial is fully accrued. CYCLONE 3 takes things even earlier in the metastatic hormone-sensitive setting for patients with high-risk disease in combination with abiraterone. We’re going to see how the story shakes out with CDK4/6 inhibitors.

Transcript edited for clarity.

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