- Most patients with advanced cholangiocarcinoma (CCA) harbouring rearrangements or fusions of the fibroblast growth factor receptor 2 (FGFR2) gene had partial responses or stable disease with pemigatinib, a selective oral inhibitor of FGFR1, FGFR2, and FGFR3.
Why this matters
- Second-line chemotherapies for locally advanced or metastatic cholangiocarcinoma have shown limited efficacy, with a median overall survival of 6.2-7.2 months and objective response rates of 7.7%-9.5%.
- From 10% to 16% of patients with intrahepatic CCA harbor mutations or rearrangements of FGFR2 that are actionable.
- Pemigitinib is a selective, potent, oral inhibitor of FGFR1, FGFR2, and FGFR3 with potential antineoplastic activity and 6 clinical trials ongoing or recruiting.
- FIGHT-202 is a phase 2 open-label, single-group study evaluating the efficacy and safety of pemigatinib in patients with previously treated locally advanced or metastatic CCA and documented FGF/FGFR gene status.
- Most patients had ECOG status 0 or 1 and intrahepatic location of their CCA.
- 3 cohorts with:
- A. FGFR2 fusions/rearrangements (n=107).
- B. Other FGF/FGFR genetic alterations (n=20).
- C. No FGF/FGFR genetic alterations (n=18).
- All received 13.5 mg pemigatinib daily (2 weeks on, 1 week off).
- The primary endpoint was overall response rate (ORR). Secondary endpoints were duration of response, disease control rate (DCR), PFS, OS, and safety.
- Funding: Incyte Corporation.
- All patients in cohorts B and C discontinued treatment, whereas at data cutoff (March 22, 2019), 31 patients in cohort A still received treatment.
- There were no complete responses (CRs) or partial responses (PRs) in cohorts B and C; 3 CRs (2.8%) and 35 PRs (32.7%) in cohort A.
- Median duration of response in cohort A was 7.5 months; DCR 82%.
- Median PFS in cohort A was 6.9 months; in cohort B, 2.1 months; and in cohort C, 1.7 months.
- Median OS in cohort A was 21.1 months vs 6.7 months and 4.0 months in cohorts B and C, respectively.
- "I think we must applaud the investigators. It was a huge effort to collect more than 100 patients with rare genetic changes in a subgroup of patients with a rare disease. FGFR inhibition in patients with FGFR rearrangement is very promising," said Per Pfeiffer, MD, PhD, from Odense University Hospital, Denmark, who was not involved in the study.