Title: 1390P Evaluation of event-free survival as a trial-level surrogate for overall survival for patients with gastric and gastroesophageal junction adenocarcinoma in neoadjuvant/adjuvant settings
Abstract: Overall survival (OS) is the standard endpoint in oncology trials but often requires prolonged follow-up. Event-free survival (EFS) is a well-accepted endpoint in early-stage oncology trials and a common surrogate endpoint for OS in neoadjuvant and adjuvant cancer therapy. This study aims to evaluate the trial-level association between EFS and OS for patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma in neoadjuvant/adjuvant settings. A systematic literature review was conducted in December 2020 to identify randomized clinical trials (RCTs) of a neoadjuvant therapy (± an adjuvant therapy) in gastric or GEJ adenocarcinoma. Full-text articles with no publication date restriction and conference abstracts from 2018 were reviewed. Though the terminology used for EFS varied, the definitions for events were similar across studies, including disease progression, local or distant recurrence, and death. Treatment effects on EFS and OS were measured as hazard ratios (HRs) between a pair of randomized arms. A weighted linear regression of log(HR) of OS on log(HR) of EFS was performed. The coefficient of determination (R2) and the associated 95% confidence interval (CI) were used to measure the association between the treatment effects on EFS and OS. Sensitivity analyses (SAs) were conducted to assess the association in the RCTs that included a mixed population of patients with esophageal, gastric or GEJ adenocarcinoma, evaluated both neoadjuvant and adjuvant chemotherapy, or measured EFS and OS from neoadjuvant therapy initiation. The study included 18 comparisons from 17 RCTs. The primary analysis indicated that 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). In the SAs, R2 ranged from 0.76 to 0.89. The strongest association was observed in a subgroup of RCTs that measured EFS and OS from neoadjuvant therapy initiation (R2 = 0.89, 95% CI, 0.66-0.98). The findings suggest that EFS is a good surrogate for OS in gastric or GEJ adenocarcinoma in neoadjuvant/adjuvant settings.