Front Immunol. 2026 Jul 10;17:1855859. doi: 10.3389/fimmu.2026.1855859. eCollection 2026.
ABSTRACT
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Immune checkpoint inhibitor (ICI) monotherapy has shown limited efficacy in PDAC, whereas the potential clinical value of first-line ICI-based combination regimens remains unclear. Through a systematic review and meta-analysis, this study aimed to evaluate the efficacy and safety of first-line ICI-based combination regimens in advanced PDAC.
METHODS: PubMed, Embase, The Cochrane Library, Scopus, Web of Science, CNKI, Wanfang Data, VIP, and CBM were searched up to April 4, 2026, to identify clinical studies evaluating first-line ICI-based combination therapy for advanced PDAC. Study screening and data extraction were performed in accordance with PRISMA guidelines.
RESULTS: Eight clinical trials involving 379 patients were included. In RCT-only analyses, ICI-based combination regimens showed favorable but statistically non-definitive trends for OS (HR = 0.83, 95% CI: 0.65-1.06) and PFS (HR = 0.75, 95% CI: 0.53-1.05), while ORR was improved (OR = 2.19, 95% CI: 1.32-3.64). Single-arm pooled analysis showed a median PFS of 6.2 months and an ORR of 38.0%. In terms of safety, combination therapy increased the risk of specific Grade 3 or higher adverse events, but the overall incidence was clinically manageable.
CONCLUSION: First-line ICI-based combination regimens showed encouraging antitumor activity in advanced PDAC, particularly for radiological response. However, definitive survival benefits were not established in RCT-only analyses, and further large-scale randomized trials are needed.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261440306, identifier CRD420261440306.
PMID:42500667 | PMC:PMC13396027 | DOI:10.3389/fimmu.2026.1855859
