Real-world efficacy of immune checkpoint inhibitors in microsatellite unstable/mismatch repair-deficient biliary tract cancer: An AGEO study
Menée en France à partir de données portant sur 48 patients atteints d'un cancer des voies biliaires de stade avancé avec déficience du système de réparation des mésappariements de l'ADN ou haute instabilité des microsatellites (durée médiane de suivi : 25,1 mois), cette étude rétrospective analyse l'efficacité, du point de vue du taux de réponse globale, du taux de contôle de la maladie, de la survie sans progression, et la toxicité des inhibiteurs de points de contrôle immunitaire
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.
European Journal of Cancer , résumé, 2025