Which Combo Regimen for Newly Diagnosed Metastatic Prostate Cancer?

Gerald Chodak, MD


March 09, 2018

Hello. I am Dr Gerald Chodak for Medscape. Today's topic is the changing approach to managing men with newly diagnosed metastatic [prostate cancer]. The US Food and Drug Administration (FDA) issued a new approval for abiraterone plus prednisone to be used in combination with castration for men with two of the following three characteristics: Gleason score > 7, at least three lesions on bone scan, and evidence of visceral metastases.

This is based on a randomized trial[1] in patients randomized to receive either castration plus placebo or castration plus abiraterone and prednisone. With a median follow-up of 30.4 months, median survival was 34.7 months in the placebo group; median survival had not yet been reached in the group receiving the combination therapy. It translated into about a 38% reduction in mortality. Secondary endpoints also showed a significant advantage in favor of the combination therapy.

Side effects that were important included hypokalemia and hypertension, which occurred significantly more often in the group getting the combination treatment.

Several comments are worth mentioning. First, the idea of using combined androgen blockade is not new. Back in the 1990s, 27 randomized trials were conducted looking at an antiandrogen in combination with castration. Only three of those showed a significant improvement in survival. Many people were very skeptical of the concept of combining an antiandrogen and castration.

What was not well appreciated at the time the studies were done, however, is the concept of the antiandrogen withdrawal phenomenon. None of the studies were conducted taking that into account. In other words, men were continued on the antiandrogen even when it was causing progression of the disease. The fact that any study showed an improvement in survival is really quite surprising. Now we have proof of concept that indeed an antiandrogen in addition to castration does convey an advantage for patients.

The second comment has to do with management of newly diagnosed metastatic disease. We have evidence from other randomized trials that adding docetaxel with castration in men with high-risk metastases also conveys a survival advantage. For the time being, we are left with the question: Which combination therapy should patients be offered? One way of deciding may be by considering differences in side-effect profiles and also the idea that the docetaxel will be more self-limited in terms of duration of therapy compared with combining abiraterone and castration.

Nevertheless, this is not a bad problem to have. It does require that clinicians be able to discuss both of the options with their patients carefully. Hopefully, one day we will see a head-to-head comparison, but at the end of the day, the differences between these two therapies may not be very great.

The bottom line is that this is an important advance in the management of men with prostate cancer who have metastases, and hopefully this progress will continue.

I look forward to your comments. Thank you.


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