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Published on: July 31, 2016
Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement:
Tanios S Bekaii-Saab1, Davide Melisi2, Hanneke Wilmink3
1Mayo Clinic, Phoenix, AZ.
Purpose:
Cholangiocarcinoma is a rare cancer associated with poor prognosis. Pemigatinib was the first FGFR1-3 inhibitor approved for second-line therapy and beyond, on the basis of the phase II FIGHT-202 trial. Here, we assess efficacy and safety of first-line pemigatinib.
Methods:
FIGHT-302 is a phase III, randomized, global trial evaluating pemigatinib as first-line therapy (ClinicalTrials.gov identifier: NCT03656536). Adults with advanced cholangiocarcinoma with FGFR2 rearrangement were randomized 1:1 to receive pemigatinib (13.5 mg once daily) or chemotherapy (1,000 mg/m2 gemcitabine plus 25 mg/m2 cisplatin once per day on days 1 and 8 of every 3-week cycle for ≤8 cycles) and were stratified by prior receipt of chemotherapy, geographic region, and tumor burden. Pemigatinib crossover was allowed for patients progressing on chemotherapy. The primary end point was progression-free survival (PFS). Secondary efficacy, safety, and exploratory end points were also analyzed.
Results:
Overall, 4,563 patients were prescreened, 196 were screened, and 167 randomly assigned to receive pemigatinib (n = 83) or chemotherapy (n = 84) before early closure of the study because of a change in standard of care. The median PFS was 8.3 months in the pemigatinib group versus 6.8 months in the chemotherapy group (hazard ratio, 0.58 [95% CI, 0.39 to 0.87]; nominal P = .0078); objective response rate was 47% versus 15%, and the median duration of response was 14.2 versus 6.3 months. Median overall survival was similar (24.4 v 25.0 months, respectively). In the crossover group (n = 42, second-line pemigatinib), the median PFS was 8.1 months. Safety was consistent with the known profile of pemigatinib.
Conclusion:
To our knowledge, this was the largest, first-line, randomized, phase III trial of a targeted therapy for advanced FGFR2-rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.
Insights
First-line pemigatinib significantly improved progression-free survival in advanced cholangiocarcinoma patients with FGFR2 rearrangements compared to chemotherapy. This targeted therapy showed improved response rates without new safety concerns.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Cholangiocarcinoma (CCA) is a rare cancer with a poor prognosis.
- Pemigatinib is an approved FGFR1-3 inhibitor for second-line CCA treatment.
- Limited data exists on pemigatinib as a first-line therapy for CCA.
Purpose of the Study:
- To evaluate the efficacy and safety of first-line pemigatinib in advanced cholangiocarcinoma (CCA) with FGFR2 rearrangements.
- To compare pemigatinib against standard chemotherapy in the first-line setting.
Main Methods:
- A phase 3, randomized, global trial (FIGHT-302) enrolled adults with advanced CCA and FGFR2 rearrangements.
- Patients were randomized 1:1 to receive pemigatinib or chemotherapy (gemcitabine/cisplatin).
- Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and objective response rate (ORR).
Main Results:
- The study randomized 167 patients to pemigatinib (n=83) or chemotherapy (n=84).
- Median PFS was significantly longer with pemigatinib (8.3 months) versus chemotherapy (6.8 months) (HR, 0.58; P=0.0078).
- Objective response rate was higher with pemigatinib (47%) compared to chemotherapy (15%), with a longer duration of response.
Conclusions:
- First-line pemigatinib demonstrated superior progression-free survival compared to chemotherapy in patients with FGFR2-rearranged advanced cholangiocarcinoma.
- Pemigatinib showed a favorable safety profile consistent with previous findings.
- This trial represents the largest first-line randomized study of targeted therapy for this specific patient population.
