A clinical trial reported on at the 2017 American Society of Clinical Oncology (ACSO) Annual Meeting found that men who develop metastatic hormone therapy-resistant prostate cancer (mHRPC) have similar outcomes if prescribed either abiraterone or enzalutamide. Abiraterone and enzalutamide are two hormonal therapies that can be used as first line treatment for men with mHRPC, but have never been directly compared in clinical trials. There are no tests to help patients choose between these therapies, so whichever one they receive likely depends on their physician’s familiarity with the therapy, cost and availability, or anticipated side-effects. Then, when patients develop resistance to abiraterone or enzalutamide, they are often switched over to the other. But is one any better than the other?
In a phase II clinical trial led by PCF-funded investigator Dr. Kim Chi, a medical oncologist at the Vancouver Prostate Centre and the BC Cancer Agency – Vancouver Centre, 202 mHRPC patients were randomized to receive abiraterone vs. enzalutamide as their first treatment after progressing on androgen deprivation therapy (ADT). More patients on enzalutamide had declines in PSA levels. However, there was no difference between the two therapies were when measuring time to progression, which is when the cancer is no longer being blocked by the treatment and begins growing again. Side effects of abiraterone and enzalutamide were also somewhat of a toss-up. Patients receiving enzalutamide were more likely to experience fatigue and one patient had a seizure, while patients on abiraterone were more likely to experience hypertension, low blood potassium levels, and elevated liver enzymes.
In this ongoing trial, once patients progress on abiraterone or enzalutamide, they will be switched over to the other therapy. This will address whether there is any benefit to receiving these therapies in any particular order. In addition, PCF Young Investigator Dr. Alexander Wyatt, also of the Vancouver Prostate Centre, is leading an effort to evaluate mutations in tumors from the patients on these trials, to determine if there are any markers that can be used to indicate that a patient will benefit more from one or the other of these therapies.
The findings that abiraterone and enzalutamide are equivalent in halting mHRPC progression is not surprising as clinical trials performed in similar patient populations suggested similar survival benefits. However, head-to-head randomized clinical trials are the only way to definitively compare the efficacy of two treatments. Likely, the findings from this study will lead to a continuation in how treatment choices are made for mHRPC when choosing between abiraterone and enzalutamide — familiarity, cost and availability, and side-effects being the key deciding factors.