Enzalutamide reduces risk of death in men with nmCRPC by 27% vs placebo

Enzalutamide (XTANDI) treatment reduced risk of death in patients with nonmetastatic castration-resistant prostate cancer and rapidly rising prostate-specific antigen (PSA) by 27% compared to placebo, according to research presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

Enzalutamide, an androgen receptor inhibitor, is indicated for the treatment of men with castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. This final analysis of the phase 3 PROSPER study supports enzalutamide and androgen deprivation therapy as the standard of care to improve overall survival in prostate cancer patients before the onset of detectable metastasis.

“This is great news for urologists who see patients with this type of disease. The data are reassuring that patients with nonmetastatic castration-resistant prostate cancer and a rapidly rising PSA have a safe and effective option that improves overall survival by almost 1 year,” according to the study’s lead author Cora N. Sternberg, MD, of Weill Cornell Medicine, New York-Presbyterian in New York City.

The Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer, or PROSPER, is a randomized, double-blind, placebo-controlled, multinational trial of about 1400 men with nonmetastatic castration-resistant prostate cancer. Patients had no evidence of metastatic disease, but their prostate cancer had progressed based on a rising PSA.

Researchers evaluated treating patients with once-daily 160 mg oral enzalutamide and androgen deprivation therapy vs placebo and androgen deprivation therapy.

PROSPER had previously shown enzalutamide resulted in a significant and clinically meaningful lower risk of radiographic progression or death, improvement in metastasis-free survival, of 71% compared to placebo. Overall survival data were immature when the investigators first reported their findings.

In this final overall survival analysis, median overall survival was 67.0 months among men who received enzalutamide compared to 56.3 months in the placebo arm. Sternberg and colleagues reported a median follow up of 48 months. Of 466 deaths, 288, or 30.9%, were in the enzalutamide arm vs 178, or 38.0%, in the placebo group.

Enzalutamide treatment resulted in 11 months of additional survival benefit for patients, according to Sternberg.

“Subsequent antineoplastic therapies were initiated after treatment discontinuation by 310 (33%) men in the enzalutamide arm vs 390 (84%) in the [placebo] arm. This includes patients who crossed over to receive enzalutamide. Median duration of treatment was 33.9 mo vs 14.2 mo with enzalutamide vs [placebo], respectively,” according to the presentation.

Forty-eight percent of men in the enzalutamide arm and 27% in the placebo arm reported grade 3 or higher adverse events, including falls, fatigue, and hypertension. In the enzalutamide arm, 16% of adverse events were drug-related vs 6% in the placebo arm.

“The safety profile was consistent with the established safety profile of enzalutamide. These data should be reassuring to colleagues who are interested in overall survival data and this is a confirmation of metastasis-free survival results,” Sternberg said.

Disclosure: Pfizer and Astellas Pharma funded the trial. Dr. Sternberg has been a consultant to Astellas Pharma, AstraZeneca, Bayer, Incyte, Merck, MSD, Pfizer, Roche, Roche-Genentech, Clovis and Sanofi-Genzyme. For full disclosures, click here.