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Advancing precision immunotherapy in advanced pancreatic cancer: a systematic review and meta-analysis of first-line ICI-based combinations

In brief

First-line immunotherapy combos achieve 38% response rate in advanced pancreatic cancer

In a meta-analysis of eight trials (379 patients), ICI-based combination regimens produced an overall response rate of 38%, roughly twice the response seen with checkpoint inhibitor monotherapy, and a median progression-free survival of about 6 months. Survival trends favored the combos but did not reach statistical significance, and higher-grade toxicities were more common yet manageable; larger randomized trials are required to confirm a survival benefit.

Journal
Frontiers in immunology (Q1)
Published
10 July 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Xiaoqi Qi, Haoran Yang, Li Zhang, Peishi Yu, Can Cheng
PMID
42500667
DOI
10.3389/fimmu.2026.1855859

Why clinicians should know about it

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.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.