Medivation and Astellas Pharma announced results from their Phase 3 PREVAIL trial of Xtandi (enzalutamide) in patients with chemotherapy-naive metastatic prostate cancer who have failed androgen deprivation therapy and have few or no symptoms. Xtandi is an oral androgen receptor signaling inhibitor that prevents testosterone from binging to androgen receptors, nuclear translocation of androgen receptors, and DNA binding and activation by androgen receptors.

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The Phase 3 PREVAIL trial was a randomized, double-blind, placebo-controlled, multi-national study of 1,700 male patients with metastatic prostate cancer whose disease progressed despite treatment with androgen deprivation therapy. The participants had not yet received chemotherapy. The co-primary endpoints of the trial were overall survival and radiographic progression-free survival.

The results were as follows:

  • Enzalutamide demonstrated a statistically significant overall survival benefit compared with placebo. Enzalutamide reduced the risk of death by 29% (HR=0.71; P<0.0001), compared with placebo. This benefit was observed despite substantial use of subsequent therapies (40% in the enzalutamide and 70% in the placebo groups).
  • Significantly reduced the risk of radiographic progression or death by 81% compared with placebo (HR=0.19; P<0.0001). 
  • Consistent benefits on these co-primary endpoints of overall survival and radiographic progression-free survival were observed across patient subgroups.
  • Men taking enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared with men taking placebo (28.0 months v.s 10.8 months; HR=0.35; P<0.0001).
  • The majority of men (58.8%) with soft tissue metastatic disease treated with enzalutamide vs. 5% of patients treated with placebo had objective responses (complete responses or partial responses) including complete responses in 19.7% of enzalutamide patients compared with 1% of placebo patients.
  • Enzalutamide extended the median time to PSA progression from 2.8 months (placebo) to 11.2 months (HR=0.169; P<0.0001).
  • Nearly 4 out of 5 patients in the enzalutamide group experienced a PSA decline of 50% or more, compared to less than 4% in the placebo group (78% vs. 3.5%; P<0.0001).
  • The median times to deterioration in a measure of prostate cancer-specific quality of life, the Functional Assessment of Cancer Therapy-Prostate or FACT-P, were 11.3 months for the enzalutamide-treated patients and 5.6 months for the placebo patients (HR= 0.625, P<0.0001).
  • The median treatment duration for enzalutamide was more than 3 times longer than for placebo (16.6 vs. 4.6 months).

On August 31, 2012, the FDA approved Xtandi for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel.

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