507 Background: Cholangiocarcinoma (CCA), categorized as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA), is often diagnosed at an advanced or metastatic stage. Approximately, 10-15% of iCCA harbor mutations in isocitrate dehydrogenase 1 ( IDH1 ) gene. However, data on real-world clinical outcomes and treatment patterns remain scarce. This study aims to provide a better understanding of the management of patients (pts) with m IDH1 CCA. Methods: This retrospective study utilized Citizen Health data, a real-world dataset harmonized across 3000 healthcare institutions, to evaluate United States CCA pts’ basic characteristics, molecular testing data, and treatment patterns. Pts were followed from the date of initial pathologic diagnosis until death or censored at the last activity in the database. In addition to the descriptive analysis, time-to-event endpoints were estimated using Kaplan-Meier (KM). Results: 602 pts diagnosed with CCA from 2007 to 2025 were included; 59.8% were female, median (range) age was 59.5 (22.3-85.8) years; 157 pts (26.1%) had ECOG performance Status 0 and 236 pts (39.2%) of 1. Most pts had iCCA (61.0%) and advanced or metastatic disease (59.8%) at diagnosis. The majority of pts (n=499, 82.9%) underwent biomarker testing. For 395 pts (79.2%), the testing was tissue-based and, for 106 pts (21.2%), it was performed on liquid biopsy. The main method used was next-generation sequencing (NGS) for 275 pts (55.1%) and immunohistochemistry (IHC) for 194 pts (38.9%). Among pts evaluated for IDH1 alterations, 88 pts (18.6%) had m IDH1 CCA with 60 pts (68.2%) diagnosed with advanced/metastatic disease. 80 pts (90.9%) received first-line (1L) systemic therapy for any stage, including gemcitabine-cisplatin (GemCis) (n=26, 32.5%) or GemCis-durvalumab (n=21, 26.3%) and GemCis-nab-paclitaxel (n=12, 15.0%). In the 1L, median (m) PFS was 8.0 months (mo), mOS was 30.0 mo, and disease control rate (DCR) was 84%. 63 pts (71.6%) received second-line (2L) therapy, including ivosidenib monotherapy (n=22; 34.9%) or in combination (n=7, 11.1%). In the 2L, in pts who received ivo-containing regimens (n=29), mPFS was 6.1 mo, mOS was 25.1 mo, and DCR was 69%; while in pts who received other regimens (n=34), mPFS was 4.1 mo, mOS was 20.1 mo, and DCR was 56%. Conclusions: Most pts with CCA were diagnosed with advanced or metastatic disease and the majority of pts had access to biomarker testing. Pts with m IDH1 CCA received mainly GemCis or GemCis-durvalumab as 1L therapy and ivosidenib as 2L therapy as recommended by current guidelines. mOS was longer than expected in each line of treatment, potentially due to survivorship bias, self-selection bias, and a limited number of pts harboring IDH1 mutations. This real-world study corroborates the efficacy finding from ClarIDHy and supports ivosidenib as a valuable 2L treatment option for patients with m IDH1 CCA.
Shroff et al. (Sat,) studied this question.