Evaluation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Localized Pancreatic Cancer:...

Overall survival (OS) is considered the reference-standard endpoint for assessing treatment efficacy in oncology but requires prolonged follow-up evaluation. This study assessed progression-free survival (PFS) as a surrogate endpoint for OS in patients with localized pancreatic ductal adenocarcinoma (PDAC).

This retrospective international multicenter study included patients with a diagnosis of localized PDAC who were treated with at least one cycle of (m)FOLFIRINOX (2012-2022). Surrogacy between PFS and OS was assessed at the individual level using the Kendall rank correlation coefficient (Kendall's τ), with a τ of 0.8 considered the threshold for good surrogacy.

This study analyzed 1783 patients with a median age of 64.0 years, and 43.4% underwent surgical resection. The median OS was 22.2 months, and the median PFS was 12.8 months. Kendall's τ was 0.647 (95% confidence interval [CI], 0.626-0.668) overall and was higher for patients with lower baseline tumor burdens (primarily resectable [0.730], borderline resectable [0.640], locally advanced [0.601]), and more favorable pathologic responses (from 0.822 for ypT0 to 0.535 for ypT3-4, and from 0.755 for ypN0 to 0.541 for ypN2). The median post-progression survival was 6.7 months (interquartile range, 3.3-13.4 months).

Individual-level surrogacy between PFS and OS did not meet the prespecified threshold for good surrogacy due to considerable interpatient variability in post-progression survival, supporting the continued use of OS as the gold-standard efficacy endpoint in clinical trials. However, surrogacy was stronger among patients with lower pretreatment tumor burdens and more favorable pathologic responses, potentially facilitating perioperative treatment development through shorter follow-up periods in pancreatic cancer trials.