Real-world survival outcomes with ivosidenib in Chinese patients with IDH1-mutated intrahepatic cholangiocarcinoma.

Abstract

e16227 Background: The phase III ClarIDHy trial led to FDA approval of ivosidenib as a therapeutic option for locally advanced or metastatic cholangiocarcinoma (CCA) patients with isocitrate dehydrogenase 1 (IDH1) mutations. However, data regarding its efficacy and safety in Chinese population remains limited. Methods: We retrospectively analyzed survival outcomes of patients with locally advanced or metastatic IDH1-mutated intrahepatic cholangiocarcinoma (iCCA) treated with ivosidenib in clinical practice at our center from January 2019 to January 2025. Ivosidenib was administered at a standard dose of 500mg once daily in 28-days cycles. Molecular profiling was performed using next-generation sequencing. Results: As of January 20, 2025, five patients were included in the study. The cohort comprised predominantly men (60%) with a median age of 69 years (range: 54-78). At baseline, the overall Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of patients is 1-2, with 80% of patients having a score of 2. All patients were diagnosed with metastatic iCCA, with liver and lymph node metastases being most common (60% each). The IDH1 mutation type identified in all 5 patients was R132C missense mutation, and 3 patients reported traceable molecular analysis, highlighting TP53, ALK and ARID1A as the most common co-altered genes in these patients. Ivosidenib was administered as first-line therapy in 1 patient (20%), second-line therapy in 3 patients (60%) and third-line therapy in 1 patient (20%). At the data cutoff, two patients (40%) were long-term survivors (alive≥1 year) and their survival follow-up is ongoing. The median progression-free survival (PFS) from initiation of treatment with ivosidenib was 5.1 months (range: 2.0-28.5), and the median overall survival (OS) was 9.5 months (range: 3.2-30.5), regardless of the treatment line. One patient (20%) achieved a partial response (PR), while four patients (80%) maintained stable disease (SD) as their best response. Treatment-emergent adverse events (AEs) were reported in one patient, all of which were grade 1, including diarrhea, rash, and oral mucositis. Conclusions: This preliminary data suggested the clinical benefit of ivosidenib for metastatic IDH1-mutated iCCA in the Chinese population. Further multi-center studies with larger cohorts are warranted to validate these findings and explore the broader applicability of ivosidenib in this patient population. Start of ivosidenib regardless of treatment line. Patient ID Extent of disease Setting Best response Survival PFS (months) OS (months) IDH1 mutation Concomitant genetic alterations 1 IV II L PR Yes 4.6 15.3 R132C TP53 2 IV III L SD Yes 28.5 30.5 R132C ALK, ARID1A 3 IV I L SD No 2 3.2 R132C NA 4 IV II L SD No 5.1 9.5 R132C TP53 5 IV II L SD No 4.1 4.1 R132C NA