- The open-label, multinational, phase 2 FOENIX-CCA2 trial evaluated futibatinib for treatment of unresectable or metastatic intrahepatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements
- 42% of 103 patients had an objective response, median duration of response 9.7 months, and responses were consistent across pre-specified subgroups, including patients ≥65 years old and those with heavily pretreated disease
- At median follow-up of 17 months, median progression-free survival was 9 months and overall survival was 21.7 months
- The most common grade 3 adverse events were hyperphosphatemia (30% of patients), increased aspartate aminotransferase level (7%), stomatitis (6%) and fatigue (6%); treatment-related events led to permanent futibatinib discontinuation in only 2%
- On the basis of these results, futibatinib received accelerated FDA approval for treatment of advanced FGFR2 fusion/rearrangement positive intrahepatic cholangiocarcinoma
Fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements occur in up to 14% of patients with intrahepatic cholangiocarcinoma, a rare, aggressive cancer with poor prognosis. Two FGFR1–3 inhibitors, pemigatinib and infigratinib, are FDA-approved for this disease, but they bind reversibly to the FGFR kinase domain and resistance mutations often develop.
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Futibatinib is an irreversible inhibitor of FGFR1–4 and less susceptible to on-target resistance mutations. Lipika Goyal, MD, a physician–investigator at the Mass General Cancer Center, is part of a multinational team whose phase 2 trial led to accelerated FDA approval of futibatinib for patients with advanced FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma. Details appear in The New England Journal of Medicine.
The open-label FOENIX-CCA2 trial was sponsored by Taiho Oncology and Taiho Pharmaceutical. 103 adults were enrolled at 47 sites across 13 countries between April 16, 2018, and November 29, 2019. Eligibility criteria were unresectable or metastatic FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma, disease progression after systemic therapy (no previous FGFR inhibitor), adequate organ function and ECOG performance status 0 or 1.
Patients received oral futibatinib 20 mg/day in a continuous regimen. At data-cutoff on October 1, 2020, median follow-up was 17 months and median duration of treatment was nine months.
The efficacy results were:
- Objective response (primary endpoint)—42% of patients
- Complete response—1%
- Disease control—83%
- Median duration of response—9.7 months
- Median progression-free survival—9.0 months
- 12-month PFS rate—40%
- Median overall survival—21.7 months
- 12-month OS rate—72%
Responses were consistent across pre-specified subgroups, including patients ≥65 years old, those with heavily pretreated disease and those with co-occurring TP53 mutations.
56% of patients had a treatment-related grade 3 adverse event and 1% had a grade 4 AE (increased alanine aminotransferase level). The most common grade 3 AEs was hyperphosphatemia (30% of patients), defined as serum phosphate of 7mg/dL or more. The other most common grade 3 AEs were increased aspartate aminotransferase level (7%), stomatitis (6%) and fatigue (6%).
Serious events occurred in 10% of patients, but treatment-related AEs led to permanent discontinuation of futibatinib in only 2%.
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