What question did this study set out to answer?

This research aims to characterize the prevalence and treatment patterns of IDH1 mutations in biliary tract cancer patients.

January 14, 2026

Isocitrate dehydrogenase 1 mutations in biliary tract cancer patients in Spanish RETUD registry.

Key Points

This research aims to characterize the prevalence and treatment patterns of IDH1 mutations in biliary tract cancer patients.
Evaluated a real-world cohort of biliary tract cancer patients from the Spanish RETUD registry.
Determined IDH1 status using next-generation sequencing, immunohistochemistry, and pyrosequencing.
Collected data on demographics, clinical characteristics, and treatment outcomes.
16.4% of patients had pathogenic IDH1 mutations, with R132C being the most common mutation.
Median progression-free survival for patients with IDH1 mutations was 8.3 months.
Patients with IDH1 mutations treated with anti-IDH1 therapy had longer survival trends.

Abstract

500 Background: Isocitrate dehydrogenase 1 mutations (IDH1mut) define a distinct molecular subtype of biliary tract cancer (BTC). We characterized the epidemiology of a cohort of BTC patients (pt) harboring pathogenic IDH1mut, treatment patterns and efficacy outcomes (EO). Methods: We evaluated a real-world pt cohort from the Spanish RETUD registry, diagnosed with BTC between January 1st, 2017, and May 30th, 2025. IDH1 status was assessed by next-generation sequencing (NGS), polymerase chain reaction (PCR), immunohistochemistry (IHQ), or pyrosequencing (PSQ). Data included demographic and clinical characteristics, molecular profile, therapeutic procedures, and EO (objective response rate ORR, overall survival OS and progression-free survival PFS). PFS and OS were estimated using the Kaplan-Meier method. Results: IDH1 status was determined in 445 pt from 31 centers. Among them, 73 (16.4%) presented pathogenic IDH1mut, with R132C mutation present in 53.4%. For IDH1mut pt, median (m) age at diagnosis (dx) was 64.5 years (y), 65.7% were women and the most frequent tumor location at dx was intrahepatic (91.8%). Among all pt with intrahepatic tumors, 24.2% harbored an IDH1mut. Metastatic disease occurred in 77.8% of all patients (78.1% in IDH1mut). Surgery was performed in 33.0% (21.9% IDH1mut) and locoregional therapy in 11.2% (9.6% IDH1mut). Systemic treatment was administered to 98.7% (100.0% IDH1mut), and 20.0% received immunotherapy. Among IDH1mut pt, 27.4% received anti-IDH1 therapy. Most frequent schemes for first and second line were CISGEM (71.6%) and FOLFOX (41.2%) respectively. With a m (min, max) follow-up time of 16.7 (0.9, 81.2) months (mo), mOS in IDH1mut vs IDH1 wild type (wt) were 20.2 mo (95% CI 17.8-28.6) and 18.4 mo (95% CI 16.5–20.4) (p=0.270). mOS in IDH1mut pt not treated with anti-IDH1 therapies was 20.0 mo (95% CI 17.1-28.6) compared to 18.4 mo (95% CI 16.5-20.4) in IDH1wt pt (p=0.450) and 26.1 mo (95% CI 17.8-54.0) in IDH1mut treated pt (p=0.530). First line mPFS and ORR were 8.3 mo (95% CI 7.7-9.5) and 22.4% in IDH1mut vs 6.1 mo (95% CI 5.4-7.3) and 28.9% in IDH1wt, respectively. A total of 49 (67.1%) IDH1mut patients presented co-expression with other biomarkers, 8 of them ESCAT-I. The most frequent co-mutations were CDKN2A (20.4%), CDKN2B (16.3%) and ARID1A (16.3%). Mutations of genes involved in RAS/MAPK signaling pathway like KRAS, BRAF and ERBB2 were less frequent in IDH1mut pt than in IDH1wt pt (10.2% vs 23.8%, 6.1% vs 6.7% and 4.1% vs 9.2% respectively). Regarding TP53/RB pathway, frequency was lower in IDH1mut pt for TP53 (10.2% vs 36.5%) and MDM2 (4.1% vs 4.4%) but not for CDKN2A/B (36.7% vs 34.2%). Conclusions: This analysis provides insights into the characterization of real-world IDH1 BTC pt. Patients receiving anti-IDH1 therapies showed a trend towards improved survival.

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