TY - JOUR
T1 - Disease-free survival as a surrogate endpoint for overall survival in adults with resectable esophageal or gastroesophageal junction cancer
T2 - A correlation meta-analysis
AU - Ajani, Jaffer A.
AU - Leung, Lisa
AU - Singh, Prianka
AU - Kurt, Murat
AU - Kim, Inkyu
AU - Pourrahmat, Mir Masoud
AU - Kanters, Steve
N1 - Funding Information:
The authors received medical writing support for the preparation of this manuscript provided by Evidinno Outcomes Research Inc. (Vancouver, BC, Canada), funded by Bristol Myers Squibb.
Funding Information:
This study was funded by Bristol Myers Squibb .
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/7
Y1 - 2022/7
N2 - Objectives: To evaluate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) using aggregate-level data from resectable esophageal or gastroesophageal junction cancer (EC/GEJC) trials assessing therapies in (neo)adjuvant and perioperative settings. Methods: A systematic literature review was conducted to identify trials reporting OS and DFS, or compatible progression-free survival (PFS). Bivariate random-effects meta-analysis was used to estimate correlation between the treatment effects on DFS/PFS and OS, and weighted linear regression models assuming trial sample sizes as weights were used to estimate surrogacy equations. The primary analysis consisted of trials across all treatment settings, and secondary analysis consisted of trials only in the adjuvant setting. Leave-one-out cross-validation (LOOCV) was performed to measure the stability and predictive accuracy of the surrogacy equations while surrogate threshold effects (STE)—the minimum treatment effect on DFS/PFS that would translate into a positive OS benefit—were derived to measure their usefulness. Results: The primary analysis included 26 trials. The estimated correlation coefficient between the hazard ratio (HR) of DFS/PFS (HRDFS/PFS) and HR of OS (HROS) was 0.83 (95% confidence interval [CI]: 0.70–0.90). The estimated surrogacy equation was log(HROS) = 0.80 × log(HRDFS/PFS) with a corresponding STE of 0.82. Reported HROS was within the 95% prediction interval of the predicted HROS from the model for more than 95% of the trials in the LOOCV, indicating a valid model. Secondary analysis included 7 trials with an estimated correlation coefficient of 0.76 (95% CI: 0.18–0.95). Through LOOCV, the surrogacy equation in the adjuvant setting was deemed valid. Conclusions: Our meta-analysis suggests that HRDFS/PFS —where DFS/PFS is defined as time from resection to disease recurrence (local, locoregional, or distant) or death—is correlated to HROS, and a valid and useful surrogate predictor for HROS in the neoadjuvant, perioperative, or adjuvant settings.
AB - Objectives: To evaluate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) using aggregate-level data from resectable esophageal or gastroesophageal junction cancer (EC/GEJC) trials assessing therapies in (neo)adjuvant and perioperative settings. Methods: A systematic literature review was conducted to identify trials reporting OS and DFS, or compatible progression-free survival (PFS). Bivariate random-effects meta-analysis was used to estimate correlation between the treatment effects on DFS/PFS and OS, and weighted linear regression models assuming trial sample sizes as weights were used to estimate surrogacy equations. The primary analysis consisted of trials across all treatment settings, and secondary analysis consisted of trials only in the adjuvant setting. Leave-one-out cross-validation (LOOCV) was performed to measure the stability and predictive accuracy of the surrogacy equations while surrogate threshold effects (STE)—the minimum treatment effect on DFS/PFS that would translate into a positive OS benefit—were derived to measure their usefulness. Results: The primary analysis included 26 trials. The estimated correlation coefficient between the hazard ratio (HR) of DFS/PFS (HRDFS/PFS) and HR of OS (HROS) was 0.83 (95% confidence interval [CI]: 0.70–0.90). The estimated surrogacy equation was log(HROS) = 0.80 × log(HRDFS/PFS) with a corresponding STE of 0.82. Reported HROS was within the 95% prediction interval of the predicted HROS from the model for more than 95% of the trials in the LOOCV, indicating a valid model. Secondary analysis included 7 trials with an estimated correlation coefficient of 0.76 (95% CI: 0.18–0.95). Through LOOCV, the surrogacy equation in the adjuvant setting was deemed valid. Conclusions: Our meta-analysis suggests that HRDFS/PFS —where DFS/PFS is defined as time from resection to disease recurrence (local, locoregional, or distant) or death—is correlated to HROS, and a valid and useful surrogate predictor for HROS in the neoadjuvant, perioperative, or adjuvant settings.
KW - Disease-free survival
KW - Esophageal cancer
KW - Gastroesophageal junction cancer
KW - Meta-analysis
KW - Overall survival
KW - Surrogacy
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U2 - 10.1016/j.ejca.2022.04.027
DO - 10.1016/j.ejca.2022.04.027
M3 - Article
C2 - 35605522
AN - SCOPUS:85130831534
SN - 0959-8049
VL - 170
SP - 119
EP - 130
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -