ASCO 2014. Abstact 5054. Sensitivity analyses for radiographic progression-free survival (rPFS): Results from the phase 3 PREVAIL trial comparing enzalutamide to placebo.
Michael J. Morris, Yohann Loriot, Tomasz M. Beer, Celestia S. Higano, Andrew J. Armstrong, Cora N. Sternberg, Johann Sebastian De Bono, Bertrand F. Tombal, Sarah B. Noonberg, Harry H. Mansbach, Suman Bhattacharya, Frank Perabo, De Phung, Dana E. Rathkopf; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Department of Cancer Medicine, INSERM U981, Gustave Roussy, Cancer Campus, Grand Paris, Villejuif, France; Oregon Health & Science University, OHSU Knight Cancer Institute, Portland, OR; Fred Hutchinson Cancer Research Center, Seattle, WA; Duke University, Durham, NC; Hospital San Camillo-Forlanini, Rome, Italy; The Royal Marsden NHS Foundation Trust, Surrey, United Kingdom; Division of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Medivation, Inc., San Francisco, CA; Astellas Pharma Global Development, Inc., Northbrook, IL; Astellas Pharma Global Development, Inc., Leiderdorp, Netherlands; Memorial Sloan Kettering Cancer Center, New York, NY
Background: In the PREVAIL trial, enzalutamide (ENZ), an androgen receptor inhibitor, significantly improved overall survival (HR: 071, P<0.0001) and rPFS (HR: 0.19, P<0.0001) compared with placebo in asymptomatic/mildly symptomatic chemotherapy-naive men with mCRPC (Beer, ASCO GUCS 2014, LBA1). Sensitivity analyses (SA) were performed to assess the impact of different sources of progression on the prespecified rPFS analysis. We also analyzed concordance between central and local reviewers.
Methods: In this double-blind, placebo-controlled, multinational study (NCT01212991), 1,717 patients were randomized 1:1 to ENZ 160 mg/day (n=872) or placebo (n=845). rPFS was a co-primary endpoint defined as time from randomization to the earliest objective evidence of radiographic progression by central review or death within 169 days of treatment discontinuation. Radiographic progression was defined by PCWG2 guidelines for bone disease or by RECIST 1.1 for soft tissue disease; bone progression was captured using a validated bone scan data capture assay. The primary rPFS analysis was event driven (at least 410 events).
Results: Concordance between central and local assessment of progression was 87.6%. Results of the SA were statistically significant in favor of ENZ.
Conclusions: rPFS sensitivity analyses in PREVAIL demonstrated a consistent and robust treatment benefit with ENZ. Central and local assessment showed good concordance using a quantitative definition of radiographic progression and validated bone scan data assay.