Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer

A meta-analysis

Koji Oba, Xavier Paoletti, Steven Robert 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 journalArticle

62 Citations (Scopus)

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

Fingerprint

Disease-Free Survival
Stomach Neoplasms
Meta-Analysis
Survival
Adjuvant Chemotherapy
Randomized Controlled Trials
Confidence Intervals
Cytotoxins
Regression Analysis
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer : A meta-analysis. / Oba, Koji; Paoletti, Xavier; Alberts, Steven Robert; Bang, Yung Jue; Benedetti, Jacqueline; Bleiberg, Harry; Catalano, Paul; Lordick, Florian; Michiels, Stefan; Morita, Satoshi; Ohashi, Yasuo; Pignon, Jean Pierre; Rougier, Philippe; Sasako, Mitsuru; Sakamoto, Junichi; Sargent, Daniel; Shitara, Kohei; Van Cutsem, Eric; Buyse, Marc; Burzykowski, Tomasz.

In: Journal of the National Cancer Institute, Vol. 105, No. 21, 06.11.2013, p. 1600-1607.

Research output: Contribution to journalArticle

Oba, K, Paoletti, X, Alberts, SR, Bang, YJ, Benedetti, J, Bleiberg, H, Catalano, P, Lordick, F, Michiels, S, Morita, S, Ohashi, Y, Pignon, JP, 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, vol. 105, no. 21, pp. 1600-1607. https://doi.org/10.1093/jnci/djt270
Oba, Koji ; Paoletti, Xavier ; Alberts, Steven Robert ; Bang, Yung Jue ; Benedetti, Jacqueline ; Bleiberg, Harry ; Catalano, Paul ; Lordick, Florian ; Michiels, Stefan ; Morita, Satoshi ; Ohashi, Yasuo ; Pignon, Jean Pierre ; Rougier, Philippe ; Sasako, Mitsuru ; Sakamoto, Junichi ; Sargent, Daniel ; Shitara, Kohei ; Van Cutsem, Eric ; Buyse, Marc ; Burzykowski, Tomasz. / Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer : A meta-analysis. In: Journal of the National Cancer Institute. 2013 ; Vol. 105, No. 21. pp. 1600-1607.
@article{c5fc1f34b62c4a82a05b9e8761c28d1e,
title = "Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer: A meta-analysis",
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.",
author = "Koji Oba and Xavier Paoletti and Alberts, {Steven Robert} and Bang, {Yung Jue} and Jacqueline Benedetti and Harry Bleiberg and Paul Catalano and Florian Lordick and Stefan Michiels and Satoshi Morita and Yasuo Ohashi and Pignon, {Jean Pierre} and Philippe Rougier and Mitsuru Sasako and Junichi Sakamoto and Daniel Sargent and Kohei Shitara and {Van Cutsem}, Eric and Marc Buyse and Tomasz Burzykowski",
year = "2013",
month = "11",
day = "6",
doi = "10.1093/jnci/djt270",
language = "English (US)",
volume = "105",
pages = "1600--1607",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "21",

}

TY - JOUR

T1 - Disease-free survival as a surrogate for overall survival in adjuvant trials of gastric cancer

T2 - A meta-analysis

AU - Oba, Koji

AU - Paoletti, Xavier

AU - Alberts, Steven Robert

AU - Bang, Yung Jue

AU - Benedetti, Jacqueline

AU - Bleiberg, Harry

AU - Catalano, Paul

AU - Lordick, Florian

AU - Michiels, Stefan

AU - Morita, Satoshi

AU - Ohashi, Yasuo

AU - Pignon, Jean Pierre

AU - Rougier, Philippe

AU - Sasako, Mitsuru

AU - Sakamoto, Junichi

AU - Sargent, Daniel

AU - Shitara, Kohei

AU - Van Cutsem, Eric

AU - Buyse, Marc

AU - Burzykowski, Tomasz

PY - 2013/11/6

Y1 - 2013/11/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84890468324&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890468324&partnerID=8YFLogxK

U2 - 10.1093/jnci/djt270

DO - 10.1093/jnci/djt270

M3 - Article

VL - 105

SP - 1600

EP - 1607

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 21

ER -