[overall survival] to accelerate drug development. (J. Clin. Oncol. 2015 Jan. 26 [doi:10.1200/JCO.2014.55.3875]). There exists a specific unmet need to validate a reproducible assay that can be interpreted and reported consistently and quantitatively as a biomarker in the assessment of bone disease (the vast majority of men with mCRPC have significant bone disease that leads to their death) with radionuclide bone scans.
A Prostate Cancer Working Group 2 (PCSG2) proposal to use a time-to-event progression endpoint for bone scan interpretation – with progression defined as two or more new lesions on an initial post treatment bone scan, followed by two additional lesions on the subsequent scan – was evaluated along with a bone scan data capture assay developed through the Prostate Cancer Clinical Consortium in COU-AA-302.
In the trial chemotherapy-naive men were randomly assigned to receive 1,000 mg abiraterone plus prednisone daily or prednisone alone.
When rPFS was based on investigator-reviewed assessments of scans at the first analysis, the decrease in the hazard of radiographic progression or death in the abiraterone group vs. the prednisone-only group was similar at 51%. At the second interim analysis for overall survival, 607 rPFS events were observed on investigator review. Treatment with abiraterone plus prednisone led to a 47% reduction in the risk of radiographic progression or death, compared with prednisone.
The this study – the first to use rPFS as a registration endpoint for evaluating chemotherapy-naive mCRPC men per FDA provides the highest level of evidence to date that rPFS is highly associated with overall survival.
Morris and his associates said that “the rigor of the independently validated data showing significant benefit in rPFS and a strong trend in [overall survival] as co-primary endpoints in combination with clinically relevant secondary endpoints” supported the regulatory approval of abiraterone acetate plus prednisone in chemotherapy-naive mCRPC patients.
“The results suggest that this objective, prospectively defined endpoint may serve as a response indicator biomarker that is evaluable in future studies,” they said, adding that while the findings demonstrate a highly positive association between rPFS and overall survival in mCRPC, they do not provide support for the use of rPFS as a substitute for overall survival.
This study was supported by Ortho Biotech Oncology Research and Development, the Prostate Cancer Clinical Trials Consortium, sponsored by the Department of Defense, and by Janssen Global Services.
rPFS May Predict Treatment Response in mCRPC Trials
Frontline Medical News · January 27, 2015
Joel T. Nowak, M.A., M.S.W.