Cholangiocarcinoma (CCA) is the most common primary malignancy of the bile duct. Standard first-line treatment for advanced or metastatic CCA is gemcitabine and cisplatin. Second-line treatments have shown limited efficacy, with median PFS ranged from 2.6 to 3.2 months, median OS from 6.2 to 7.2 months, and ORR from 7.7 to 9.5%. Several actionable oncogenes have been identified in CCA, including FGFR2 alterations. The phase 2 FIGHT-202 study was designed to evaluate the efficacy and safety of pemigatinib, a selective inhibitor of FGFR1, 2, and 3, in patients with previously treated advanced or metastatic CCA. The study enrolled 1206 patients and identified 127 patients with FGFR2 alterations. The objective response rate in the 107 patients with FGFR2 fusions (cohort A) was 35.5%, and the disease control rate was 82%. By contrast, no responses were observed in the 20 patients enrolled in cohort B (other FGF/FGFR genetic alterations) or 18 patients in cohort C (no FGF/FGFR alterations). Median PFS was 6.9 months in cohort A, 2.1 months in cohort B, and 1.7 months in cohort C. These results demonstrate pemigatinib could be a new treatment option for patients with previously treated advanced or metastatic CCA and FGFR2 fusions. A phase 3 study is ongoing to evaluate pemigatinib versus gemcitabine plus cisplatin in the first-line setting.
Source : Vogel A, Sahai V, Hollebecque A, et al. Presented at: 2019 ESMO Congress; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA40.