Wainberg Zev A, Xie Jipan, Valderrama Adriana, Yin Lei, Zhang Shujing, Shih Chie-Schin, Bhagia Pooja, Gu Qianqian, Shitara Kohei, Janjigian Yelena Y, Tabernero Josep
UCLA School of Medicine, Los Angeles, California.
Analysis Group, Inc., Los Angeles, California.
Clin Cancer Res. 2023 Apr 3;29(7):1360-1367. doi: 10.1158/1078-0432.CCR-22-2920.
This study assessed the trial-level association between event-free survival (EFS) and overall survival (OS) in gastric or gastroesophageal junction (GEJ) adenocarcinoma in the neoadjuvant ± adjuvant settings.
A systematic literature review was conducted to identify randomized controlled trials (RCT) that evaluated neoadjuvant therapies with or without adjuvant therapies for gastric or GEJ adenocarcinoma. A meta-analysis was performed using weighted linear regressions of the treatment effect of OS on the treatment effect of EFS. The coefficient of determination (R²) and associated 95% confidence interval (CI) were used to evaluate the association between treatment effects of EFS and OS. The threshold used for defining good trial-level surrogacy was a correlation coefficient (R) of 0.8 or R² of 0.65, based on prior literature. Sensitivity analyses were performed to assess the robustness of the association with divergent study designs, including study population, inclusion of adjuvant therapy, and definitions of EFS and OS.
The main analysis included 16 comparisons from 15 RCTs. The log(HR) of EFS was a significant predictor of log(HR) of OS, with an estimated coefficient of 0.72 (P < 0.001) and R² = 0.75 (95% CI, 0.49-0.95), indicating that EFS was a good surrogate outcome for OS. The results of the sensitivity analyses were consistent with the primary results, with R² ranging from 0.76 to 0.89.
This study suggests that EFS is a good surrogate for OS in gastric or GEJ adenocarcinoma in the neoadjuvant ± adjuvant setting.
本研究评估了在新辅助±辅助治疗背景下，胃癌或胃食管交界（GEJ）腺癌的无事件生存期（EFS）与总生存期（OS）之间的试验水平关联。
进行了一项系统文献综述，以确定评估胃癌或GEJ腺癌新辅助治疗（无论有无辅助治疗）的随机对照试验（RCT）。使用OS治疗效果对EFS治疗效果的加权线性回归进行荟萃分析。决定系数（R²）和相关的95%置信区间（CI）用于评估EFS和OS治疗效果之间的关联。根据先前文献，用于定义良好试验水平替代指标的阈值是相关系数（R）为0.8或R²为0.65。进行敏感性分析以评估与不同研究设计（包括研究人群、辅助治疗的纳入以及EFS和OS的定义）之间关联的稳健性。
主要分析纳入了15项RCT的16项比较。EFS的log(HR)是OS的log(HR)的显著预测因子，估计系数为0.72（P < 0.001），R² = 0.75（95% CI，0.49 - 0.95），表明EFS是OS的良好替代结局。敏感性分析结果与主要结果一致，R²范围为0.76至0.89。
本研究表明，在新辅助±辅助治疗背景下，EFS是胃癌或GEJ腺癌中OS的良好替代指标。
