Prostate cancer agent meets key endpoints in pre-chemo setting

A phase III trial of enzalutamide (Xtandi) in chemotherapy-naïve patients with advanced prostate cancer has met both of its primary endpoints in an interim analysis, and the trial will be stopped early due to the drug’s benefit.

Given the observed benefits in the trial’s co-primary endpoints of overall survival and radiographic progression-free survival, and considering the observed safety profile, the Independent Data Monitoring Committee (IDMC) concluded enzalutamide demonstrated a favorable benefit-risk ratio. The IDMC recommended that the study, known as PREVAIL, be stopped and patients treated with placebo be offered enzalutamide.

Additional data from the phase III PREVAIL results, including safety data, will be submitted for presentation at an upcoming medical conference, according to a statement from Medivation, Inc. and Astellas Pharma Inc., which are jointly commercializing enzalutamide in the United States.

The PREVAIL trial includes more than 1,700 men with metastatic prostate cancer that has progressed despite androgen deprivation therapy and who have not yet received chemotherapy. The planned interim analysis showed:

• Patients treated with enzalutamide demonstrated a statistically significant overall survival advantage compared with patients receiving placebo (p<.0001). Enzalutamide provided a 30% reduction in risk of death compared with placebo (Hazard Ratio: 0.70; 95% confidence interval: 0.59-0.83).

• Patients treated with enzalutamide demonstrated a statistically significant radiographic progression-free survival advantage compared with those receiving placebo (p<.0001). Enzalutamide provided an 81% reduction in risk of radiographic progression or death compared with placebo (HR: 0.19; 95% CI: 0.15-0.23).

• The percentage of patients alive in the enzalutamide arm was 72% as compared with 65% in the placebo arm at the time of the interim analysis data cut-off date. Treatment with enzalutamide resulted in a calculated point estimate for median overall survival of 32.4 months (95% CI: 31.5 months-upper limit not yet reached) versus 30.2 months (95% CI: 28.0 months-upper limit not yet reached) for patients receiving placebo.

• Given the overall survival benefit and the observed safety profile, the IDMC considered the overall benefit-risk ratio to favor the enzalutamide arm and recommended unequivocally that patients receiving placebo be offered treatment with enzalutamide.

Of the 1,715 patients treated in the blinded PREVAIL study, two patients were reported by investigators to have had a seizure event. The full analysis of the safety data will become available upon final database lock and unblinding.

“To my knowledge, the benefits in overall survival and radiographic progression-free survival reported in today’s PREVAIL trial results are unprecedented in this patient population,” said Tomasz M. Beer, MD, of the Knight Cancer Institute at Oregon Health & Science University, Portland, and the co-principal investigator of the PREVAIL study.

Medivation and Astellas said they will initiate meetings with and submissions to regulatory agencies beginning in early 2014. Enzalutamide was granted FDA approval in 2012 and is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel (Taxotere).

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