COMMENTARY

Combo Data Creates New Choices in Metastatic Prostate Cancer

Gerald Chodak, MD

Disclosures

August 21, 2017

Hello. I am Dr Gerald Chodak, speaking for Medscape. This week I want to again discuss the management of men with newly diagnosed metastatic prostate cancer. Traditionally, we have used androgen deprivation therapy (ADT) alone for this population of men. Two years ago, however, a randomized trial[1] demonstrated that adding chemotherapy with docetaxel to the ADT significantly improves survival.

Now, a new study demonstrates a slightly different outcome. In June, Fizazi and colleagues[2] reported on 1200 men who were randomly assigned to receive either ADT alone or ADT combined with abiraterone acetate plus prednisone. To be enrolled in this trial, patients had to have two of the following three high-risk characteristics: a Gleason score of 8 to 10, at least three bone metastases, or at least three visceral metastases.

The study currently has a median follow-up of 30.4 months. Median survival is 34.7 months in the control arm but has not yet been reached in the combination therapy arm. In other words, 50% of the patients who received abiraterone plus prednisone have not yet died. There was also a significant delay in tumor progression in the abiraterone-plus-prednisone group.

These results present an important paradigm shift, yet again demonstrating that ADT alone for high-risk metastatic prostate cancer will no longer be the primary therapy for men with newly diagnosed metastatic prostate cancer; they should be offered a combination therapy regimen. However, with two sets of findings demonstrating that ADT alone is not sufficient, we are left with a question. Now what do we do?

Should men receive ADT combined with docetaxel or should they receive ADT combined with abiraterone acetate plus prednisone? Without a prospective, randomized trial specifically addressing this question, we will have to weigh the pros and cons of each approach in terms of the duration of therapy, side effects, and cost. Of importance, in the most recent trial, the incidence of high blood pressure, low potassium levels, and impaired liver function was higher in the men taking abiraterone acetate plus prednisone compared with controls.

We now recognize that, at least for the high-risk metastatic disease group, ADT alone is no longer the optimal therapy. Nearly two decades ago, a number of studies demonstrated improved survival when ADT was combined with an antiandrogen.[3] Now that we have more effective antiandrogens, we see further improvements in the overall outcomes and perhaps more studies will be done. But going forward, we have this unanswered question: Which combination is the best approach for men with newly diagnosed, high-risk metastatic disease? For now, both options should at least be discussed as patients make their decision about treatment.

I look forward to your comments. Thank you.

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