SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1569884
This article is part of the Research TopicImmune Checkpoints Regulatory Mechanisms and Immunotherapy Strategies in Gastrointestinal TumorsView all 10 articles
Immune Checkpoint Inhibitors in Pancreatic Adenocarcinoma: A Systematic Review and Meta-Analysis of Clinical Outcomes
Provisionally accepted
- 1College of Medicine, Qatar University, Doha, Qatar
- 2Clinical Translational Science, QU Health, Qatar University, Doha, Qatar
- 3Department of Math and Statistics, College of Art and Science, Qatar University, Doha, Qatar
- 4Qatar University, Doha, Qatar
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Background: 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.We systematically reviewed and meta-analyzed clinical outcomes of ICI therapy in PDAC using studies from PubMed, CINAHL, Cochrane Library, and Google Scholar, published up to February 28, 2024. Eligible studies reported objective response rate (ORR), progression-free survival (PFS), or overall survival (OS). Risk of bias was assessed using RoB 2.0 and ROBINS-I.Random-effects models estimated pooled effect sizes.Results: Fifty-four studies (n = 2, 364) were included. 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 OS when combined with chemotherapy (HR = 0.82; 95% CI: 0.78-0.87). However, ICIs plus radiotherapy were associated with increased mortality (HR = 1.18; 95% CI: 1.04-1.34). PFS improved in select subgroups, particularly in patients with high tumor mutational burden or mismatch repair deficiency.ICIs combined with chemotherapy may modestly improve survival in PDAC.Outcomes remain heterogeneous and limited, underscoring the need for better biomarker-driven patient selection and more effective combination strategies.
Keywords: Pancreatic ductal adenocarcinoma (PDAC), Immune checkpoint inhibitors (ICIs), Tumor mutational burden, combination therapy, Survival outcomes
Received: 02 Feb 2025; Accepted: 10 Jul 2025.
Copyright: © 2025 Al-Khinji, Malouche, Al Korbi, Al Kuwari and Al Hor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Aisha Al-Khinji, College of Medicine, Qatar University, Doha, Qatar
Dhafer Malouche, Department of Math and Statistics, College of Art and Science, Qatar University, Doha, Qatar
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