Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: A meta-analysis

Koji Oba, Xavier Paoletti, Steven Alberts, Yung Jue Bang, Jacqueline Benedetti, Harry Bleiberg, Paul Catalano, Florian Lordick, Stefan Michiels, Satoshi Morita, Yasuo Ohashi, Jean Pierre Pignon, Philippe Rougier, Mitsuru Sasako, Junichi Sakamoto, Daniel Sargent, Kohei Shitara, Eric Van Cutsem, Marc Buyse, Tomasz Burzykowski

Research output: Contribution to journalReview article

73 Scopus citations

Abstract

Background In investigations of the effectiveness of surgery and adjuvant chemotherapy for gastric cancers, overall survival (OS) is considered the gold standard endpoint. However, the disadvantage of using OS as the endpoint is that it requires an extended follow-up period. We sought to investigate whether disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant chemotherapy for gastric cancer. Methods The GASTRIC group initiated a meta-analysis of individual patient data collected in randomized clinical trials comparing adjuvant chemotherapy vs surgery alone for patients with curatively resected gastric cancer. Surrogacy of DFS was assessed through the correlation between the endpoints as well as through the correlation between the treatment effects on the endpoints. External validation of the prediction based on DFS was also evaluated. Results Individual patient data from 14 randomized clinical trials that included a total of 3288 patients were analyzed. The rank correlation coefficient between DFS and OS was 0.974 (95% confidence interval [CI] = 0.971 to 0.976). The coefficient of determination between the treatment effects on DFS and on OS was as high as 0.964 (95% CI = 0.926 to 1.000), and the surrogate threshold effect based on adjusted regression analysis was 0.92. In external validation, the six hazard ratios for OS predicted according to DFS were in very good agreement with those actually observed for OS. Conclusions DFS is an acceptable surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant setting.

Original languageEnglish (US)
Pages (from-to)1600-1607
Number of pages8
JournalJournal of the National Cancer Institute
Volume105
Issue number21
DOIs
StatePublished - Nov 6 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Oba, K., Paoletti, X., Alberts, S., Bang, Y. J., Benedetti, J., Bleiberg, H., Catalano, P., Lordick, F., Michiels, S., Morita, S., Ohashi, Y., Pignon, J. P., Rougier, P., Sasako, M., Sakamoto, J., Sargent, D., Shitara, K., Van Cutsem, E., Buyse, M., & Burzykowski, T. (2013). Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: A meta-analysis. Journal of the National Cancer Institute, 105(21), 1600-1607. https://doi.org/10.1093/jnci/djt270