Radiographic progression-free survival as a response biomarker in metastatic castration-resistant prostate cancer: COU-AA-302 results - Abstract

PURPOSE: Progression-free survival (PFS) in metastatic castration-resistant prostate cancer (mCRPC) trials has been inconsistently defined and poorly associated with overall survival (OS). A reproducible quantitative definition of radiographic PFS (rPFS) was tested for association with a coprimary end point of OS in a randomized trial of abiraterone in patients with mCRPC.

PATIENTS AND METHODS: rPFS was defined as ≥ two new lesions on an 8-week bone scan plus two additional lesions on a confirmatory scan, ≥ two new confirmed lesions on any scan ≥ 12 weeks after random assignment, and/or progression in nodes or viscera on cross-sectional imaging, or death. rPFS was assessed by independent review at 15% of deaths and by investigator review at 15% and 40% of deaths. rPFS and OS association was evaluated by Spearman's correlation.

RESULTS: A total of 1,088 patients were randomly assigned to abiraterone plus prednisone or prednisone alone. At first interim analysis, the hazard ratio (HR) by independent review was 0.43 (95% CI, 0.35 to 0.52; P < .001; abiraterone plus prednisone: median rPFS, not estimable; prednisone: median rPFS, 8.3 months). Similar HRs were obtained by investigator review at the first two interim analyses (HR, 0.49; 95% CI, 0.41 to 0.60; P < .001 and HR, 0.53; 95% CI, 0.45 to 0.62; P < .001, respectively), validating the imaging data assay used. Spearman's correlation coefficient between rPFS and OS was 0.72.

CONCLUSION: rPFS was highly consistent and highly associated with OS, providing initial prospective evidence on further developing rPFS as an intermediate end point in mCRPC trials.

Written by:
Morris MJ, Molina A, Small EJ, de Bono JS, Logothetis CJ, Fizazi K, de Souza P, Kantoff PW, Higano CS, Li J, Kheoh T, Larson SM, Matheny SL, Naini V, Burzykowski T, Griffin TW, Scher HI, Ryan CJ   Are you the author?
Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Janssen Research & Development, Los Angeles; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; Institute for Cancer Research and Royal Marsden Hospital, Sutton, United Kingdom; MD Anderson Cancer Center, Houston, TX; Institut Gustave Roussy, University of Paris Sud, Villejuif, France;University of Western Sydney School of Medicine, Ingham Institute, Liverpool, New South Wales, Australia; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; University of Washington, Seattle, WA; Janssen Research & Development, Raritan, NJ; and Tomasz Burzykowski, International Drug Development Institute, Louvain-la-Neuve, Belgium. .

Reference: J Clin Oncol. 2015 Jan 26. (Epub ahead of print)
doi: 10.1200/JCO.2014.55.3875

PubMed Abstract
PMID: 25624432