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Enzalutamide vs Apalutamide, Darolutamide, and Bicalutamide for Nonmetastatic CRPC

February 23, 2021


Tomasz Beer, MD, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, discusses results from a network meta-analysis comparing the efficacy of enzalutamide vs apalutamide, darolutamide, and bicalutamide for the treatment of nonmetastatic castration-resistance prostate cancer (CRPC).

These results were presented at the virtual 2021 ASCO Genitourinary Cancers Symposium.


Hi, I'm Tom Beer. I'm a professor of medicine and deputy director of the Cancer Institute at Oregon Health and Science University. I'm pleased to be here with you today to talk about our presentation at the 2021 ASCO GU meeting.

As you probably know, in the last 2 to 3 years, we've seen the publication of 3 pivotal clinical trials that have shown that potent androgen receptor antagonists, enzalutamide, darolutamide, and apalutamide, have a positive impact on outcomes in patients with nonmetastatic castration‑resistant prostate cancer.

These are patients who are on hormonal therapy, don't have any visible metastases, but now have a rising PSA despite a castrate testosterone. 

Three large, randomized studies have shown that darolutamide, apalutamide, and enzalutamide all improve metastasis‑free survival and overall survival. All three agents have been approved for use in the United States in this indication.

We don't have any analyses that compare these agents to one another directly. Physicians and payers are faced with a decision about which agent to prefer without direct comparative data. In that situation, a network meta‑analysis is one approach to evaluating agents used in a similar indication and studied in a similar way.

We did that kind of analysis with a focus of comparing enzalutamide to the other drugs. We relied on data from the three pivotal trials, PROSPER, SPARTAN, and ARAMIS that examined enzalutamide, apalutamide, and darolutamide compared to placebo. We also included data from the STRIVE clinical trial, which compared enzalutamide to a first‑generation androgen receptor antagonist, bicalutamide.  

What we found in our analysis, not surprisingly, was that enzalutamide performed better than placebo. We already knew that, but the analysis showed that again. We looked at metastasis‑free survival, overall survival, time to chemotherapy, and time to PSA progression. On all four of those endpoints, of course, enzalutamide performed better than placebo.

We also found that, for time to PSA progression and metastasis‑free survival, enzalutamide performed better than darolutamide. Not unexpectedly, for several endpoints, enzalutamide also performed better than bicalutamide. The one exception to that is we did not have survival data for overall survival with bicalutamide, so we were not able to make that comparison.

There were no significant differences between enzalutamide and apalutamide in our analysis. What we concluded is that enzalutamide performed comparably to apalutamide and appeared to have an advantage over darolutamide with regard to metastasis‑free survival and time to PSA progression.

Thank you very much for your attention today.

Beer TM, Saad F, Sternberg CN. Network meta-analysis (NMA) comparing the efficacy of enzalutamide versus apalutamide, darolutamide, and bicalutamide for treatment of nonmetastatic (nm) castration-resistant prostate cancer (CRPC). Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 101.

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