FGFR2+ cholangiocarcinoma: pemigatinib active as second-line treatment

More than one-third of patients with previously treated locally advanced or metastatic cholangiocarcinoma (CCA) with an FGFR2 rearrangement or fusion had durable objective responses to treatment with pemigatinib, a selective oral inhibitor of FGFR1, 2, and 3, according to findings from an open-label, single-arm phase 2 clinical trial

Results from FIGHT-202, a phase 2 study of pemigatinib as a second-line treatment for patients with advanced/metastatic or surgically unresectable CCA, were presented by Prof. Antoine Hollebecque (Gustave Roussy Cancer Center, France). Eligible patients had locally advanced or metastatic CCA despite at least 1 line of prior therapy and had their FGF/FGFR status centrally confirmed. Adequate renal function was required.

A total of 1,206 patients were screened to find 127 with FGFR2 alterations; 107 patients with FGFR2 fusions/rearrangements (cohort A), 20 patients with other FGF/FGFR genetic alterations (cohort B). An additional 18 patients were enrolled with no FGF/FGFR alterations (cohort C). Among the 107 patients in cohort A, there were 92 fusions and 15 rearrangements discovered. A total of 56 unique fusion partners were identified, the most common of which was BICC1, which occurred in 29%. Median age of the entire 146 patients enrolled was 59 years, but those in cohort A tended to be younger, said Prof. Hollebecque, with 77% being younger than 65 years, compared with 50% in cohort B and 39% in cohort C. Some 58% of patients were women (61% in cohort A), and 61% were enrolled in North America, 24% in Western Europe, and 15% in the rest of the world.

Patients in the 3 cohorts were treated with oral pemigatinib (13.5 mg) using a 2 weeks on/1 week off schedule. The study was not designed to make statistical comparisons between the 3 cohorts. The primary endpoint was the confirmed ORR in cohort A by independent central review.

Results demonstrated an objective response rate (ORR) in cohort A of 35.5% and the median duration of response was 7.5 months. In contrast, there were no responses observed in cohort B or C. The higher ORR translated into a longer median progression-free survival (PFS) in cohort A. Median PFS was 6.9 months in cohort A compared with 2.1 months in cohort B and 1.7 months in cohort C.

Overall survival (OS) data were not yet mature at the time of data cut-off (March 22, 2019), but with a median follow-up of 15.4 months and a median duration of treatment of 7.2 months, the median OS was 21.1 months in cohort A, whereas median OS was only 6.7 months in cohort B after a median follow-up of 19.9 months, and only 4.0 months in cohort C after a median follow-up of 24.2 months.

In cohort A, the 35.5% ORR consisted of 3 (2.8%) complete responses, 35 (32.7%) partial responses, and 50 (46.7%) patients with stable disease, for a disease control rate of 82%. The ORR was consistent across subgroups, including when stratified by the number of prior lines of therapy and by FGFR2 rearrangement partner.

Adverse events (AEs) were manageable and consistent with the mechanism of action of pemigatinib. The most common AE was hyperphosphatemia, which occurred in 60% of patients but no grade ≥3 cases were encountered.

Based on the results of FIGHT-202, a phase 3 study evaluating first line pemigatinib compared with standard chemotherapy (gemcitabine plus cisplatin) in patients with CCA and FGFR2 fusions/rearrangements is ongoing.

1. Vogel A et al. ESMO Congress 2019. Abstract LBA40.

Posted on 26 November 201918 March 2021