Cholangiocarcinoma (CCA), a rare and aggressive cancer of the bile ducts, is notoriously difficult to treat, especially in its advanced stages. Among the subset of patients with CCA and alterations in the IDH1 gene, targeted therapies such as ivosidenib offer new hope. Ivosidenib, an oral IDH1 inhibitor, was approved by the FDA after the pivotal ClarIDHy trial demonstrated the benefit of ivosidenib in progression-free survival (PFS), median overall survival, and objective response rate. However, real-world data on the efficacy and safety of ivosidenib have been limited. This study explored the real-world outcomes of ivosidenib in US veterans with IDH1-mutated CCA, providing valuable insights into the use of ivosidenib outside of clinical trial settings.
This study, conducted by researchers from the US Veterans Affairs (VA) health system, retrospectively analyzed data from the VA Corporate Data Warehouse (CDW). Demographic, clinical, and molecular data were obtained from the CDW, the VA Informatics and Computing Infrastructure Integrated Veteran Care Consolidated Data Sets, the VA National Precision Oncology Program database, and electronic medical records. Best response and date of progression were assessed based on review of clinical notes and radiology reports.
This study included 1094 veterans diagnosed with CCA who underwent molecular testing from August 25, 2021 (date of ivosidenib approval) to December 1, 2024. Of those patients, 82 (7.5%) had an IDH1 mutation. Among these patients, 33 (45%) received ivosidenib. The median age of patients who received ivosidenib was 71 years, with most patients (94%) starting at the standard dose of 500 mg daily. The rest of the patients began treatment at a reduced dose of 250 mg daily. Of all of the patients receiving ivosidenib, 6% achieved a partial response, and 30% had stable disease. More than half of the patients (58%) experienced progressive disease.
The median PFS for all patients treated with ivosidenib was 4.0 months, and the median overall survival was 10.5 months. The median overall survival from diagnosis was significantly longer in patients with advanced-stage CCA who received ivosidenib (25.3 months) compared with those who did not receive the drug (8.7 months) (hazard ratio, 0.43; 95% confidence interval, 0.24-0.76). This suggests that ivosidenib may contribute to extended survival in patients with IDH1-mutated advanced-stage CCA.
The safety profile of ivosidenib in this real-world cohort was consistent with clinical trial data. Only 9% of patients required dose reductions, interruptions, or discontinuation due to treatment-related toxicities.
This study highlights the potential of ivosidenib as a safe and effective option for patients with advanced IDH1-mutated CCA. As the real-world results largely mirror those of the ClarIDHy trial, these findings provide hope for improving outcomes in a challenging disease with limited therapeutic options.
Zhou KI, Baidya RN, Lin C, et al. Real world efficacy and safety of ivosidenib in US veterans with IDH1 mutated cholangiocarcinoma. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Poster 376.
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