Pemigatinib in the real-world management of advanced intrahepatic FGFR2-positive cholangiocarcinoma

Abstract

Introduction. Cholangiocarcinoma (CC) is one of the most aggressive malignant tumors of the hepatobiliary tract with a poor prognosis, especially at the late stages. The targeted therapy with pemigatinib, a selective FGFR2 inhibitor, can be administered in a proportion (10–15%) of patients with intrahepatic cholangiocarcinoma (CC) harboring FGFR2 rearrangements/fusions. Aim. To evaluate the efficacy and safety of pemigatinib in second-line and subsequent lines of therapy for chemoresistant intrahepatic cholangiocarcinoma (CC) with FGFR2 rearrangements/fusions in real-world clinical practice. Mat erials and methods. The retrospective study included 68 patients with locally advanced/metastatic CC and confirmed FGFR2 alterations. The patients received pemigatinib in a standard regimen. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were assessed. Prognostic factors were analyzed using Cox regression and subgroup analysis. R esults. The majority of patients were female (70.6%). The patients received pemigatinib as second-line (39.7%), third-line (42.6%), and as subsequent (17.7%) lines of treatment. The ORR was 28%, with no complete responses recorded. The median PFS was 10.3 months (95% CI 8.2–16.7). The median OS was 16.1 months (95% CI 12.0–21.0), with a significantly higher OS in patients who achieved an objective response: 42.5 vs. 11.9 months (p < 0.0001). AEs were reported in 91.7% of patients, severe AEs (grade ≥3) in 19% of patients (most commonly hyperphosphatemia, arthralgia, and diarrhea). Dose reductions were required by 34.5% of patients; no toxicity events led to discontinuations. AEs did not impact OS (p = 0.45). C onclusion. Pemigatinib demonstrates high efficacy and acceptable safety in patients with FGFR2-altered CC in real-world clinical practice. Achieving an objective response is a robust favorable prognostic factor. An ECOG score of 2–3 and the use of pemigatinib as third-line and subsequent lines of treatment are independently associated with poor prognosis, confirming the need for early molecular genetic testing (NGS) and timely initiation of targeted therapy.