Abstract 827: Correlation among early surrogate endpoints and survival in borderline-resectable pancreatic cancer: A trial-level meta-analysis

Abstract Background: Multiple endpoints are used as surrogates for overall survival (OS) in clinical trials for borderline resectable pancreatic cancer (BRPC), including the R0 resection rate. However, consensus is lacking regarding the validity of this and other surrogate endpoints. This study aims to assess the relationship between common surrogate endpoints and median OS (mOS). Methods: We conducted a systematic review of PubMed and Web of Science to identify clinical trials investigating neoadjuvant treatment (surgery, chemotherapy, or radiation therapy) of BRPC. Eligible trials reported on OS and at least one surrogate endpoint (resection rate [RR], R0 resection rate [R0], 1-year OS [1yOS], and 2-year OS [2yOS]). We estimated the correlation of OS with each of the surrogate endpoints using both Spearman and Pearson coefficients (r). The confidence intervals (CI) of coefficients were estimated by 2, 000 times of bootstrapping resampling. Weighted linear regressions with calculation of R-squared were utilized to estimate correlations adjusted for the sample size in each cohort. Results: We identified 25 eligible clinical trials with 32 treatment cohorts. The range of mOS was 11 to 41 months, and the median mOS was 23.3 months. R0 and 2yOS were significantly correlated with mOS by the Spearman coefficient (r=0.51 [95% CI: 0.01-0.79] and r=0.74 [0.19-0.95], respectively) but RR and 1yOS were not. All early endpoints (RR, R0, 1yOS and 2yOS) were significantly correlated with mOS by the Pearson coefficient (r=0.49 [0.01-0.79], 0.58 [0.28-0.78], 0.75 [0.12-0.91] and 0.79 [0.43-0.92], respectively). Weighted liner regression revealed that RR, R0, 1yOS and 2yOS were significantly correlated with mOS (R-squared= 0.20, 0.32, 0.43 and 0.57, respectively with p < 0.05 for all). Conclusions: This study demonstrated significant correlations between early surrogate endpoints and mOS in BRPC. However, the correlation between mOS and resection-related endpoints (RR and R0) was modest. These findings provide important context for selection and interpretation of surrogate endpoints in studies of BRPC. Citation Format: Chanbormey Leatheng, Alexander Khamechand, Gabriel A. Brooks, Hirotaka Miyashita. Correlation among early surrogate endpoints and survival in borderline-resectable pancreatic cancer: A trial-level meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 827.