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

BackgroundPancreatic 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 microen...

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Main Authors: Aisha Al-Khinji, Noora Al-Korbi, Sheikha Al-Kuwari, Abdullatif Al-Hor, Dhafer Malouche
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1569884/full
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author Aisha Al-Khinji
Aisha Al-Khinji
Noora Al-Korbi
Sheikha Al-Kuwari
Abdullatif Al-Hor
Dhafer Malouche
Dhafer Malouche
author_facet Aisha Al-Khinji
Aisha Al-Khinji
Noora Al-Korbi
Sheikha Al-Kuwari
Abdullatif Al-Hor
Dhafer Malouche
Dhafer Malouche
author_sort Aisha Al-Khinji
collection DOAJ
description BackgroundPancreatic 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.MethodsWe 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.ResultsFifty-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.ConclusionICIs 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.
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spelling doaj-art-d93a766af62840babff3080504c827ae2025-08-20T02:55:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.15698841569884Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomesAisha Al-Khinji0Aisha Al-Khinji1Noora Al-Korbi2Sheikha Al-Kuwari3Abdullatif Al-Hor4Dhafer Malouche5Dhafer Malouche6College of Medicine, Qatar University, Doha, QatarClinical Translational Science Research Group, Qatar University (QU) Health, Qatar University, Doha, QatarCollege of Medicine, Qatar University, Doha, QatarCollege of Medicine, Qatar University, Doha, QatarCollege of Medicine, Qatar University, Doha, QatarClinical Translational Science Research Group, Qatar University (QU) Health, Qatar University, Doha, QatarDepartment of Mathematics and Statistics, College of Arts and Sciences, Qatar University, Doha, QatarBackgroundPancreatic 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.MethodsWe 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.ResultsFifty-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.ConclusionICIs 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.https://www.frontiersin.org/articles/10.3389/fonc.2025.1569884/fullpancreatic ductal adenocarcinoma (PDAC)immune checkpoint inhibitors (ICIs)tumor mutational burdencombination therapysurvival outcomes
spellingShingle Aisha Al-Khinji
Aisha Al-Khinji
Noora Al-Korbi
Sheikha Al-Kuwari
Abdullatif Al-Hor
Dhafer Malouche
Dhafer Malouche
Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomes
Frontiers in Oncology
pancreatic ductal adenocarcinoma (PDAC)
immune checkpoint inhibitors (ICIs)
tumor mutational burden
combination therapy
survival outcomes
title Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomes
title_full Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomes
title_fullStr Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomes
title_full_unstemmed Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomes
title_short Immune checkpoint inhibitors in pancreatic adenocarcinoma: a systematic review and meta analysis of clinical outcomes
title_sort immune checkpoint inhibitors in pancreatic adenocarcinoma a systematic review and meta analysis of clinical outcomes
topic pancreatic ductal adenocarcinoma (PDAC)
immune checkpoint inhibitors (ICIs)
tumor mutational burden
combination therapy
survival outcomes
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1569884/full
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