Work

Progression-free survival as a surrogate for overall survival in gastro-esophageal cancer trials with immunotherapy: A meta-analysis

Year: 2025

Type: review

Study designs: Systematic Review, Meta-Analysis

Abstract: Background Immune checkpoint inhibitors (ICIs)-based regimens are the first-line standard of care for most patients with advanced gastroesophageal adenocarcinoma (GEA) and esophageal squamous cell carcinoma (ESCC). The efficacy of these treatments often depend on PD-L1 expression levels. Overall survival (OS) has traditionally been the primary endpoint for evaluating treatment efficacy. Through a meta-analysis, we investigated whether progression-free survival (PFS) is a valid surrogate for OS in the ICIs-era, overall and across different PD-L1 subgroups. Methods A systematic literature review was conducted to identify eligible randomized controlled trials (RCTs) published by 30/06/2025. Trial-level surrogacy of PFS for OS was assessed using Spearman rank correlation coefficient (R) and weighted linear regression, calculating the coefficient of determination (R 2 ). Results Eighteen eligible RCTs were evaluated. Regarding GEA, the correlation between treatment effects on PFS and on OS was moderate in the overall population (R=0.82; R 2 =0.52) and in the CPS≥1 subgroup (R=0.81; R 2 =0.66), moderate yet non-significant in the CPS<1 subgroup (R=0.67; R 2 =0.51), and strong in the CPS≥5 subgroup (R=0.77; R 2 =0.85). In ESCC, the correlation in the overall population was weak (R=0.64; R 2 =0.47). No improvement of the correlation was found in the subgroup of patients with CPS≥10 (R=0.33; R 2 =0.16) or TPS≥1% (R=0.40, R 2 =0.005). Conclusions While the correlation between treatment effects on PFS and OS was weak in ESCC, it was moderate in PD-L1-low GEA, and good in PD-L1-high GEA. Therefore, PFS is an adequate co-primary endpoint in future trials investigating novel ICIs—based regimens in GEA, especially if the analyses are pre-planned in PD-L1-high subgroups.

Source: European Journal of Cancer

DOI: 10.1016/j.ejca.2025.116155