Adding Enzalutamide to ADT Extends OS in Patients With Nonmetastatic CRPC

Adding enzalutamide to androgen deprivation therapy (ADT) led to a longer median overall survival (OS) in patients with nonmetastatic castration-resistant prostate cancer (CRPC) and a rapidly rising prostate-specific antigen (PSA) level than placebo plus ADT in a phase 3 clinical trial (N Engl J Med. 2020 May 29. Epub ahead of print).

“Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic [CRPC] and rapidly increasing [PSA] levels while taking androgen-deprivation therapy,” wrote lead investigator Cora N. Sternberg, MD, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, and colleagues.

A total of 1401 patients with nonmetastatic CRPC who were continuing ADT were included in the double-blind study. These patients were randomized in a 2:1 ratio to receive enzalutamide 160 mg (n = 933) or placebo (n = 468) once daily.

Dr Sternberg et al used a group sequential testing procedure and an O'Brien-Fleming-type alpha-spending function to evaluate OS.

Overall, 288 (31%) patients in the enzalutamide arm and 178 (38%) patients in the placebo arm died as of October 2019. The median OS for these arms was 67.0 months (95% CI, 64.0 to not reached) versus 56.3 months (95% CI, 54.4-63.0), respectively (hazard ratio for death, 0.73; 95% CI, 0.61-0.89; P = .001).

In the enzalutamide and placebo arms, adverse events grade ≥3 had exposure-adjusted rates of 17 per 100 patient-years and 20 per 100 patient-years, respectively.

According to the investigators, adverse events with enzalutamide were consistent with those previously reported for the drug, with the most common being fatigue and musculoskeletal events.

“Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level,” Dr Sternberg and colleagues wrote.

“The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide,” they concluded.—Hina Porcelli