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Multicenter Study
. 2025 Sep 9:227:115670.
doi: 10.1016/j.ejca.2025.115670. Epub 2025 Jul 30.

Real-world efficacy of immune checkpoint inhibitors in microsatellite unstable/mismatch repair-deficient biliary tract cancer: An AGEO study

Iona Campo-Le-Brun  1 , Emma Grapinet  2 , Valerie Aurillac  2 , Antoine Hollebecque  3 , Pauline Parent  4 , Paul Girot  5 , David Tougeron  6 , Mélanie Gendreau  7 , Brice Chanez  8 , Eric Assenat  9 , Simon Pernot  10 , Emily Alouani  11 , Julien Taieb  12 , Sahir Javed  13 , Yann Touchefeu  14 , Gael Roth  15 , Marie Muller  16 , Jean-Baptiste Bachet  17 , Marie Lequoy  18 , Vincent Hautefeuille  19 , Meher Ben-Abdelghani  20 , Thérèse Masson  21 , Rosine Guimbaud  22 , Alice Boilève  23 , Marie Decraecker  24
Affiliations
Multicenter Study

Real-world efficacy of immune checkpoint inhibitors in microsatellite unstable/mismatch repair-deficient biliary tract cancer: An AGEO study

Iona Campo-Le-Brun et al. Eur J Cancer. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) significantly improve survival in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI) tumors. In 2022, ICIs were approved as first-line treatment with chemotherapy for advanced biliary tract cancers (BTCs). MSI/dMMR BTC represents a rare subtype, and its response to ICIs remains poorly understood. This multicenter real-world study aimed to describe clinical characteristics and outcomes of those patients.

Methods: We retrospectively included all patients with MSI/dMMR BTC treated at 23 French centers. Primary endpoint was overall survival (mOS) from the initiation of ICIs.

Results: Between 2012 and 2023, 48 patients with MSI/dMMR BTC were included with a median follow-up of 25.1 months. Thirty-seven (77 %) patients received ICIs: 10 (27 %) in first-line combined with chemotherapy, 4 (11 %) as first-line monotherapy and 23 (62 %) in later lines (20 as monotherapy, 3 as double immunotherapy). From the initiation of ICIs, mOS was 40.9 months (CI95 %: 16.39-NR) and median progression-free survival (mPFS) was 11.24 months (CI95 %: 6.44-NR). Overall response rate was 36 % and disease control rate was 75 %. Grade 3-4 adverse events occurred in 15 % and 50 % of patients treated with ICIs without chemotherapy or with chemotherapy, respectively. Among patients with available molecular profiling (69 %), co-alterations were identified in 16 (48 %) patients, most frequently in TP53 (12 %), CDKN2A/B (12 %), KRAS (12 %), GNAS (9 %), FGFR2/3 (6 %), SMAD4 (6 %), and IDH1 (6 %) genes.

Conclusion: This first real-world cohort study of patients with MSI/dMMR BTC demonstrated that ICI-based treatment offers a prolonged response and improved survival in this subgroup of BTC.

Keywords: Biliary tract neoplasms; Cholangiocarcinoma; DNA mismatch repair; Immune checkpoint inhibitors; Microsatellite instability.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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