Final Results from the FIGHT-202 Trial of Pemigatinib in Metastatic CCA

Pemigatinib is an oral, selective fibroblast growth factor receptor (FGFR)1-3 inhibitor that was FDA-approved in April 2020 for the treatment of adults with previously treated, unresectable, locally advanced/metastatic cholangiocarcinoma (CCA) bearing an FGFR2 fusion or other rearrangement based on the FIGHT-202 trial. Final results of the FIGHT-202 trial (NCT02924376) were presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer 2022.

FIGHT-202, which is a single-arm, open-label, multicenter, phase 2 study, enrolled patients aged ≥18 years with locally advanced/metastatic or surgically unresectable CCA who progressed after ≥1 prior therapy, a documented FGF/FGFR status, ECOG performance status ≤2, and adequate hepatic/renal function. Eligible patients were assigned to 1 of 3 cohorts based on confirmed FGF/FGFR status: cohort A (FGFR2 gene rearrangements/fusions), cohort B (other FGF/FGFR gene alterations), or cohort C (no FGF/FGFR gene alterations). Patients received oral pemigatinib 13.5 mg daily (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary end point was centrally confirmed overall response rate (ORR) in cohort A; secondary end points were ORR (cohorts B and C), duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. For the post hoc analysis, case report forms were reviewed to determine disease history and exposure to prior lines of systemic cancer therapies in the advanced setting before receiving pemigatinib.

The final analysis included a total of 147 patients; of these, 108 were enrolled in cohort A, 20 in cohort B, and 17 in cohort C. Median age was 59 years (range, 26-78 years), 57.8% of patients were women, 70.7% were white, and 89.8% had intrahepatic CCA, including 99.1% of the patients in cohort A. Median duration of follow-up was 45.4 months (range, 19.9-53.7 months). In total, 105 (98.6%) patients discontinued treatment, most commonly due to disease progression (71.4%).

In cohort A, ORR was 37.0%, and DCR was 82.4%; median DOR was 9.1 months. Median PFS in cohort A was 7.0 months, and median OS was 17.5 months. Efficacy outcomes were lower in cohorts B and C. In cohort B, DCR was 40.0%, median PFS was 2.1 months, and median OS was 6.7 months. In cohort C, DCR was 17.6%, median PFS was 1.5 months, and median OS was 4.0 months.

The safety profile in the final analysis was similar to that of the primary analysis; no new safety signals were observed. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). The majority of TEAEs were grade 1 or 2 in severity; the most common grade ≥3 TEAE was hypophosphatemia (14.3%). Fatal TEAEs were reported in 4.1% of patients; none were deemed related to pemigatinib treatment. TEAEs led to treatment discontinuation in 10.2% of patients.

Based on results of the final analysis, the authors concluded that “pemigatinib continued to demonstrate durable response, prolonged OS, and a manageable safety profile in patients with advanced/metastatic CCA with FGFR2 fusions or rearrangements.”

Source: Vogel A, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated locally advanced or metastatic cholangiocarcinoma: final results from FIGHT-202. European Society for Medical Oncology World Congress on Gastrointestinal Cancer 2022. Abstract O-2.