Real-world outcomes and safety of FGFR inhibitors in intrahepatic cholangiocarcinoma: A TriNetX analysis.

Abstract

e16186 Background: Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive malignancy associated with poor prognosis and limited systemic treatment options. FGFR inhibitors are approved for previously treated iCCA harboring FGFR2 fusions or rearrangements; however, real-world effectiveness and early toxicity outside of clinical trials remain incompletely characterized. We evaluated real-world outcomes and safety of FGFR inhibitor therapy in routine clinical practice. Methods: Using TriNetX, a federated network of de-identified electronic health records from participating healthcare organizations, we identified adults (≥18 years) with iCCA (ICD-10 C22.1) who initiated pemigatinib or futibatinib on or after 04/01/2020 and had evidence of prior systemic anticancer therapy. Overall survival (OS) and time to next treatment (TTNT) were assessed using Kaplan–Meier methods, with censoring at the last recorded clinical encounter. Treatment-related safety outcomes including hyperphosphatemia, ocular toxicity, and gastrointestinal/mucositis toxicity were assessed from 0–90 days after the first FGFR inhibitor exposure; patients with the outcome prior to treatment were excluded. Exploratory subgroup analyses were performed by age ( < 65 vs ≥65 years) and sex. Results: The cohort included 237 patients (mean age 60.3±12.9 years; 57% female) with a median follow-up of 293 days (9.6 months). Common comorbidities included hypertension (43%), diabetes (25%), and chronic kidney disease (6%). There were 132 deaths, with a median OS of 364 days (12.0 months). Overall, 83 patients initiated subsequent systemic therapy, with a median TTNT of 521 days (17.1 months). Hyperphosphatemia was the most frequent early toxicity, with serum phosphate ≥4.5 mg/dL observed in 61.0% and ≥7 mg/dL in 14.4% of patients. Ocular toxicity and gastrointestinal/mucositis toxicity were identified in 9.4% and 11.8% of patients, respectively. OS and TTNT did not significantly differ by age group or sex in exploratory analyses. Conclusions: In this real-world cohort of patients with previously treated iCCA receiving FGFR inhibitors, median OS was 12 months and median TTNT was 17 months, with early toxicity predominantly characterized by hyperphosphatemia. These findings provide clinically relevant real-world context to pivotal FGFR inhibitor trials and may inform expectations regarding outcomes and toxicity monitoring in routine practice.