Clinical Cases in Advanced Prostate Cancer - Episode 7

Case 1: Antiandrogen Therapy for Nonmetastatic CRPC

December 21, 2020
Targeted Oncology

Experts in genitourinary oncology share how they decide between the 3 antiandrogen therapies for nonmetastatic castration-resistant prostate cancer: apalutamide, enzalutamide, and darolutamide.

Jorge A. Garcia, MD, FACP: It’s intriguing because I think this is one of those spaces where we didn’t have any active treatment for this patient population for many years. Right at the beginning of Mary-Ellen’s career, it actually expanded. With second-line hormonal therapies like nilutamide, flutamide, bicalutamide, and even the steroids, but none of those agents really led to survival improvement.

For registration purposes, the gold standard has always been survival for prostate cancer, until we got the data from the M0 CRPC [nonmetastatic castration-resistant prostate cancer] space…where survival became another de facto for registration, but MFS, standing for metastasis-free survival. One of the concerns a lot of people had when you look at MFS is whether that was a true surrogate for survival improvement.

Obviously now we have that survival data that we’ll review later. But Patrick, if you look at the data that we have, we have enzalutamide, apalutamide, and darolutamide—3 super active compounds. These are 3 agents that independently not only delay MFS, but led to survival improvement and met many of the secondary end points of PSA [prostate-specific antigen] decline, time to chemotherapy, time to SRE [skeletal-related event], and so on. Is there anything uniquely relevant to this case that would change your mind or allow you to select one agent over another one? And if so, why?

Patrick G. Pilié, MD:Absolutely. With these 3 agents all providing overall survival benefit, it’s a very exciting time to be treating patients with M0 castrate-resistant prostate cancer. The decision of which agent to select comes down to a patient-to-patient personalized basis. As already mentioned, the financial toxicity associated with these medications should be incorporated into the decision, but with each one having some individual [adverse] effect characteristics, that could push you toward choosing one over the other.

In this case, the patient having the history of seizure, although not fully explained in terms of the origin, would obviously push you away from choosing enzalutamide or maybe even apalutamide. Where darolutamide does not cross the blood-brain barrier, and so [adverse] effect profile-wise would probably be a better choice in this patient. Examining the patient’s comorbidities and what other medications they are on help guide the decision of which one to choose.

Transcript edited for clarity.