Early Results: Enzalutamide + ADT Delays Metastatic Prostate Cancer Progression

Gerald Chodak, MD


January 24, 2019

Hello. I'm Dr Gerald Chodak for Medscape, wishing you a happy and healthy new year. Today's topic is: improving outcomes for men with newly diagnosed metastatic prostate cancer.

It has been about 60 years since the initial discovery of androgen deprivation therapy (ADT) and about 30 years since the discovery of antiandrogens. Then, studies were conducted combining ADT and antiandrogens [for men with metastatic disease], something that was called maximum or complete androgen blockade. Although about 25 randomized studies were conducted, only three of them showed a statistically significant improvement in survival, and because of the small impact, few people adopted this strategy as a routine way to manage newly diagnosed metastatic disease.

Now we have newer antiandrogens that have a number of advantages over previous drugs. A new study has been in progress for several years; the ARCHES study is looking at the combination of ADT with the antiandrogen enzalutamide.

Men who were taking an LHRH (luteinizing hormone–releasing hormone) agonist or antagonist or who had undergone surgical castration were randomly assigned, in a double-blind fashion, to receive either placebo or enzalutamide once a day. The study is still relatively early but I want to discuss it now because the results have great potential to help a large number of men.

The primary outcome of the study was [radiographic progression-free survival]—the time until the development of metastatic disease as assessed by radiographic studies. To date, those participants who received enzalutamide had a statistically significant improvement, or prolongation, of time to radiographic progression. It's too early to assess other outcomes, but we expect more follow-up in the future. The study results have not yet been published, so we don't know how side effects were affected by combining the two drugs.

Where do we stand with this? In the past, the antiandrogens weren't strong enough [to affect outcomes], and the side-effect potential had a negative impact on it being adopted. Moreover, the antiandrogen withdrawal phenomenon was not understood until several years after many of the studies had been completed. Now with that understanding and the possibility of some antiandrogen withdrawal associated with enzalutamide, we have this new finding and we look forward to seeing further follow-up. [This approach] certainly has the potential to have a great impact on men with metastatic disease.

I look forward to your comments. Thank you.


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