E-poster Presentation 2014 World Cancer Congress

Enzalutamide in men with chemotherapy-naïve metastatic castration resistant prostate cancer (mCRPC): Primary and Australian/Asian regional results of the phase 3 PREVAIL study  (#1130)

Ian Davis 1 , Choung-Soo Kim 2 , Go Kimura 3 , Weber Lau 4 , Sarah B. Noonberg 5 , Frank Perabo 6 , Suman Bhattacharya 5 , De Phung 6 , Bertrand Tombal 7 , Tomasz M. Beer 8 , Paul N. Mainwaring 9
  1. The Austin Hospital; Austin Health, Heidelberg, AU, Australia
  2. Asan Medical Center, Seoul, South Korea
  3. Nippon Medical School Hospital, Tokyo, Japan
  4. Singapore General Hospital, Singapore
  5. Medivation, Inc., San Francisco, CA, USA
  6. Astellas Pharma , Northbrook, IL, USA
  7. University Catholique de Louvain, Brussels, Belgium
  8. Oregon Health and Science University, Portland, OR, USA
  9. Icon Cancer Care, South Brisbane, QLD, Australia

Background: The PREVAIL study examined the impact of enzalutamide on overall survival (OS) and radiographic progression-free survival (rPFS) in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients progressing despite androgen deprivation therapy.

Aim: Here we report primary outcomes from the full PREVAIL population and from the Australian/Asian cohort.

Methods: This, double-blind, placebo-controlled, multinational, Phase 3 study randomized patients 1:1 to enzalutamide 160 mg/day or placebo. OS and rPFS were co-primary endpoints. Planned sample size was 1680 (765 deaths) to achieve 80% power to detect a target OS hazard ratio (HR) of 0.815 with a 2-sided type I error rate of 0.049 and a single interim analysis at 516 (67%) deaths. The co-primary endpoint of rPFS had >99% power to detect a target HR of 0.57 and a 2-sided type I error rate of 0.001 with a minimum of 410 events.  Pre-specified analyses of patients enrolled from Australia and Asia followed the same methodologies.

Results: The PREVAIL study randomized 1717 men (1715 treated) between September 2010 and September 2012. Australia, Japan, Singapore and South Korea enrolled 380/22.1% patients (Australia, 232/13.5%; Asia 148/8.6%). Statistically significant benefits of enzalutamide over placebo were shown for both co-primary endpoints [(OS interim analysis at 540 deaths: 29% reduction in risk of death; OS: HR 0.71; 95% CI: 0.59-0.83; P< 0.0001); (the concurrent rPFS final analysis:  81% reduction in risk of radiographic progression or death; rPFS: HR 0.19; 95% CI: 0.15-0.23; P< 0.0001)] in the overall intent-to-treat population of PREVAIL.  Among Australian/Asian patients, enzalutamide demonstrated a benefit in both co-primary endpoints (OS: HR 0.62; 95% CI: 0.42-0.92; rPFS: HR 0.14; 95% CI: 0.08-0.25).

 

Conclusions: Enzalutamide significantly improved OS and rPFS in men with chemotherapy-naïve mCRPC progressing despite androgen deprivation therapy. Efficacy outcomes in the Australia/Asia subgroup were consistent with those in the overall population.