Progression-free survival as a surrogate for overall survival in advanced/recurrent gastric cancer trials: a meta-analysis

Xavier Paoletti; Koji Oba; Yung-Jue Bang; Harry Bleiberg; Narikazu Boku; Olivier Bouché; Paul Catalano; Nozomu Fuse; Stefan Michiels; Markus Moehler; Satoshi Morita; Yasuo Ohashi; Atsushi Ohtsu; Arnaud Roth; Philippe Rougier; Junichi Sakamoto; Daniel Sargent; Mitsuru Sasako; Kohei Shitara; Peter Thuss-Patience; Eric Van Cutsem; Tomasz Burzykowski; Marc Buyse; GASTRIC group

doi:10.1093/jnci/djt269

Progression-free survival as a surrogate for overall survival in advanced/recurrent gastric cancer trials: a meta-analysis

J Natl Cancer Inst. 2013 Nov 6;105(21):1667-70. doi: 10.1093/jnci/djt269. Epub 2013 Oct 9.

Affiliation

¹ Affiliations of authors: Biostatistics Department, INSEM U900 Institut Curie, Paris, France (XP); Translational Research and Clinical Trial Center, Hokkaido University Hospital, Hokkaido, Japan (KO); Seoul National University College of Medicine, Oncology Division, Seoul, Korea (Y-JB); Jules Bordet Hospital, Brussels, Belgium (HB); St. Marianna University School of Medicine, Kawasaki, Japan (NB); Hôpital Robert Debré, Reims, Department of Clinical Oncology, France (OB); Dana-Farber Cancer Institute and Harvard School of Public Health, Department of Biostatistics, Boston, MA (PC); National Cancer Center Hospital East, Department of Gastrointestinal Oncology, Kashiwa, Japan (NF, AO); Institut Gustave Roussy, Université Paris XI, Biostatistics and Epidemiology Department, Villejuif, France (SMi); Johannes Gutenberg University, Medical Department, Mainz, Germany (MM); Yokohama City University, Department of Biostatistics and Epidemiology, Kanagawa, Japan (SMo); University of Tokyo, Tokyo, Japan (YO); University Hospital, Department of Surgery, Geneva, Switzerland (AR); University Hospital Europeen Georges Pompidou, Gastro-enterology Department, Paris, France (PR); Tokai Central Hospital, Sohara, Japan (JS); Mayo Clinic, Division of Biomedical Statistics and Informatics, Rochester, MN (DS); National Cancer Center Hospital East, Kashiwa, Japan (MS); Aichi Cancer Center Hospital, Department of Gastrointestinal Oncology, Aichi, Japan (KS); Charité-Universitätsmedizin Berlin, Department of Haematology, Oncology, and Tumorimmunology, Berlin, Germany (PT-P); University Hospital Gasthuisberg, Digestive Oncology Unit, Leuven, Belgium (EVC); Hasselt University, Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Diepenbeek, Belgium (TB, MB); International Drug Development Institute, Louvain-la-Neuve, Belgium (MB).

Abstract

The traditional endpoint for assessing efficacy of chemotherapies for advanced/recurrent gastric cancer is overall survival (OS), but OS requires prolonged follow-up. We investigated whether progression-free survival (PFS) is a valid surrogate for OS. Using individual patient data from the GASTRIC meta-analysis, surrogacy of PFS was assessed through the correlation between the endpoints and through the correlation between the treatment effects on the endpoints. External validation of the prediction based on PFS was also evaluated. Individual data from 4069 patients in 20 randomized trials were analyzed. The rank correlation coefficient between PFS and OS was 0.853 (95% confidence interval [CI] = 0.852 to 0.854). The R (2) between treatment effects on PFS and on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were only moderately correlated, and we could not confirm the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cancer.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Disease-Free Survival
Humans
Neoplasm Recurrence, Local / mortality*
Neoplasm Recurrence, Local / therapy*
Odds Ratio
Predictive Value of Tests
Randomized Controlled Trials as Topic
Stomach Neoplasms / mortality*
Stomach Neoplasms / pathology
Stomach Neoplasms / therapy*
Treatment Outcome

Substances

Biomarkers

Grants and funding

U10 CA023318/CA/NCI NIH HHS/United States