Event-free survival, a prostate-specific antigen-based composite end point, is not a surrogate for overall survival in men with localized prostate cancer treated with radiation
Clarke, Noel W
AffiliationDivision of Biostatistics, Dana-Farber Cancer Institute, Boston, MA.
MetadataShow full item record
AbstractPurpose: Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)-based composite end point, may further expedite trial completion. Methods: EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate-ICECaP-database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 ? 0.7. Results: Data for 10,350 patients were analyzed from 15 radiation therapy-based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall's tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. Conclusion: EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy-based trials.
CitationXie W, Regan MM, Buyse M, Halabi S, Kantoff PW, Sartor O, et al. Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation. J Clin Oncol. 2020:JCO1903114.
JournalJournal of Clinical Oncology
- Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer.
- Authors: Xie W, Regan MM, Buyse M, Halabi S, Kantoff PW, Sartor O, Soule H, Clarke NW, Collette L, Dignam JJ, Fizazi K, Paruleker WR, Sandler HM, Sydes MR, Tombal B, Williams SG, Sweeney CJ, ICECaP Working Group.
- Issue date: 2017 Sep 20
- Multitrial Evaluation of Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Extensive-Stage Small-Cell Lung Cancer.
- Authors: Foster NR, Renfro LA, Schild SE, Redman MW, Wang XF, Dahlberg SE, Ding K, Bradbury PA, Ramalingam SS, Gandara DR, Shibata T, Saijo N, Vokes EE, Adjei AA, Mandrekar SJ
- Issue date: 2015 Jul
- Statistical controversies in clinical research: assessing pathologic complete response as a trial-level surrogate end point for early-stage breast cancer.
- Authors: Korn EL, Sachs MC, McShane LM
- Issue date: 2016 Jan
- Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Diffuse Large B-Cell Lymphoma: An Individual Patient-Level Analysis of Multiple Randomized Trials (SEAL).
- Authors: Shi Q, Schmitz N, Ou FS, Dixon JG, Cunningham D, Pfreundschuh M, Seymour JF, Jaeger U, Habermann TM, Haioun C, Tilly H, Ghesquieres H, Merli F, Ziepert M, Herbrecht R, Flament J, Fu T, Coiffier B, Flowers CR
- Issue date: 2018 Sep 1
- Validation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials.
- Authors: Wang X, Wang X, Hodgson L, George SL, Sargent DJ, Foster NR, Ganti AK, Stinchcombe TE, Crawford J, Kratzke R, Adjei AA, Kindler HL, Vokes EE, Pang H
- Issue date: 2017 Feb