Real-world outcomes to frontline standard of care gemcitabine/cisplatin plus durvalumab in IDH1 mutated advanced cholangiocarcinoma in the US.

Cholangiocarcinoma (CCA) is a rare but increasing biliary tract cancer, which is often diagnosed at advanced stages with poor 5-year survival. While chemotherapy (gemcitabine [Gem]-cisplatin [Cis]) combined with immunotherapy (durvalumab [Durva] / pembrolizumab) is the current first-line (1L) standard of care (SOC) treatment, IDH1 mutations (mIDH)—found in ∼13% of intrahepatic cases—offer a target for specialized therapy. Real-world data are essential to benchmark effectiveness of current 1L SOC in this population.

This non-interventional, retrospective study uses data from two electronic medical records in the US (ConcertAI and Ontada) for adult patients with advanced CCA diagnosed from 2015 to 2025 and tested for mIDH1. The study assesses the effectiveness in terms of real-world overall response to treatment (rwORR), progression-free survival (PFS), and overall survival (OS) of 1L Gem/Cis+Durva in mIDH1 CCA. Time to event outcomes are estimated using the Kaplan-Meier method.

The study included 333 patients, of whom 112 had mIDH1. In the mIDH1 population, 62 (55%) were treated with Gem/Cis+Durva in 1L. In the Gem/Cis+Durva mIDH1 group, 79% were female and the median age at start of 1L was 65.1 years (range 38–80), with 56.5% of patients with ECOG of 0 or 1 and 89% had an intrahepatic site. The median number of cycles was 4.4 (2.7-7.4) and the median follow-up was 11.7 months (7.6-19.1) since the start of 1L treatment. rwORR to 1L Gem/Cis+Durva was 27.4% and the disease control rate was 51.6%. 34% of patients were deceased at the end of study period. The median OS from start of 1L treatment was 18.4 months (95% CI, 13.3–NR) and median PFS was 4.9 months (95% CI, 3.5–6.3). The estimated 24-month overall survival rate was 35.0% (95% CI, 16.0%–54.8%).

Results for rwORR are consistent with the TOPAZ-1 trial findings for Gem/Cis+Durva in CCA. While median OS in this mIDH1 CCA population was higher than historical 1L benchmarks, which are likely due to the high proportion of intrahepatic disease, these trends are supported by other real-world studies. This study serves as a benchmark for the effectiveness of front-line standard of care within the specific mIDH1 advanced CCA population.