Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomes

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with poor outcomes despite therapeutic advancements. Immune checkpoint inhibitors (ICIs) have transformed cancer care, but their efficacy in PDAC is limited due to the tumor’s immunosuppressive microenvironment. This systematic review and meta-analysis evaluates clinical outcomes of ICI therapy in PDAC, using data from 54 studies comprising 2,364 patients. Objective response rates (ORR) ranged from 0% to 67%. ICI-based combinations showed a modest ORR benefit (OR = 1.10; 95% CI: 1.02–1.18) and improved overall survival (OS) when combined with chemotherapy (HR = 0.82; 95% CI: 0.78–0.87). However, combinations with radiotherapy were associated with increased mortality (HR = 1.18; 95% CI: 1.04–1.34). Progression-free survival (PFS) improved in select subgroups, particularly in patients with high tumor mutational burden or mismatch repair deficiency. The study also evaluates methodological aspects such as risk of bias using RoB 2.0 and ROBINS-I, and heterogeneity using I². The findings emphasize the limited yet evolving role of ICIs in PDAC, advocating for biomarker-driven patient selection and novel combination strategies.