Advances in the treatment of localized CaP have led to decreased recurrences and improved OS. The Intermediate Clinical Endpoints in CaP (ICECaP) Working Group is conducting meta-analysis of potential surrogate endpoints for localized CaP trials. We hypothesized that MFS is a surrogate for OS.
By June 2013, we systematically identified 102 eligible randomized trials (completed or ongoing) comparing treatments in localized CaP and collected individual patient data (IPD) from trialists. MFS was defined from randomization to the first evidence of distant metastatic disease (excluding pelvic lymph nodes), or death from any cause; or was censored at the date of last follow-up. OS was defined from randomization to death from any cause. We evaluated the surrogacy of MFS with OS using a 2-stage meta-analytic validation model where 2 conditions must hold to claim MFS is a surrogate for OS (Buyse et al, 2000 & 2011 - table). The secondary objective evaluated surrogacy of time to metastasis (TTM) with disease specific survival (DSS), defined analogously to MFS and OS but with non-CaP deaths censored.
By May 2016, IPD from 12,712 men randomized in 19 mature trials between 1987 and 2010 were available for analysis. 90% of the men were from radiation based trials, 30% had intermediate and 57% high-risk disease (NCCN criteria) and 83% were
MFS can be used as a surrogate of OS and TTM as a surrogate of DSS.
Clinical trial identification
Legal entity responsible for the study
Dana Farber Cancer Institution, Boston, MA, United States
Prostate Cancer Foundation, CA, United States
C. Sweeney: consultant with compensation - Sanofi, BIND, Janssen, Astellas, Genentech, Bayer, AZ.
H.M. Sandler: Financial: Consulting: Janssen, Sanofi, Clovis Oncology, Ferring, Eviti Non-financial: Chairman, GU Cancer Committee, NRG Oncology.
All other authors have declared no conflicts of interest.