Futibatinib confers benefit in FGFR-altered intrahepatic cholangiocarcinoma
Futibatinib demonstrated clinical benefit among previously treated patients with fibroblast growth factor receptor 2 fusion- or rearrangement-positive intrahepatic cholangiocarcinoma, according to results of a phase 2 study.
The findings of the multinational, open-label FOENIX-CCA2 study, published in The New England Journal of Medicine, also showed stable quality of life during treatment with futibatinib (Lytgobi, Taiho Oncology).
Background
Intrahepatic cholangiocarcinoma is a rare but increasingly common malignancy of the intrahepatic bile ducts and has a historically poor prognosis, Lipika Goyal, MD, gastrointestinal medical oncologist at Massachusetts General Hospital Cancer Center, told Healio.
Although surgery is the main curative option, about two-thirds of patients have disease regression, and the 5-year OS rate remains less than 8%.
“Given the limited treatment options following the failure of first-line treatment for cholangiocarcinoma, it is important to investigate novel treatment options for this group of patients based on our growing understanding for the underlying molecular biology of cancer," Goyal told Healio.
About 14% of patients with intrahepatic cholangiocarcinoma have fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements. Futibatinib, a FGFR1-4 inhibitor, has exhibited antitumor activity in patients with FGFR-altered tumors. The agent received FDA approval in September for adults with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma who harbor FGFR2 fusions or other rearrangements.
Methodology
In FOENIX-CCA2, Goyal and colleagues evaluated the efficacy and safety of futibatinib among 103 patients (median age, 58 years; range, 22-79; 56% women) with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma. All patients experienced disease progression after one of more prior lines of systemic therapy that did not include FGFR inhibitors, and 53% had received at least two previous lines of systemic therapy.
Patients received 20 mg futibatinib daily in a continuous regimen over a 21-day cycle. Treatment continued until imaging-based or clinical disease progression, unacceptable toxic effects or other causes for discontinuation.
Objective response as assessed by independent central review served as the primary endpoint, with duration of response, PFS, OS, safety and patient-reported outcomes as secondary endpoints.
Key findings
Results showed 43 patients (42%; 95% CI, 32-52) responded to futibatinib, including one complete response. Moreover, 85 patients (83%; 95% CI, 74-89) had disease control.
Researchers noted a median duration of response of 9.7 months (95% CI, 7.6-17).
Researchers reported median PFS of 9 months (95% CI, 6.9-13.1), with a 6-month PFS rate of 66% (95% CI, 56-75) and 12-month rate of 40% (95% CI, 29-51), and median OS of 21.7 months (95% CI, 14.5 to not reached), with a 12-month OS rate of 72% (95% CI, 62-80).
The most common grade 3 treatment-related adverse events included hyperphosphatemia (30%), increased aspartate aminotransferase level (7%), stomatitis (6%) and fatigue (6%).
Only 2% of patients permanently discontinued treatment due to treatment-related adverse events, and no deaths related to treatment occurred. In addition, patients maintained quality of life during treatment.
Clinical implications
The results have the potential to heavily impact treatment selection for this patient population, with futibatinib shown to be more effective than chemotherapy in some key areas, according to researchers.
“The current data from FOENIX‐CCA2 demonstrate that the paradigm of molecular targeting genomic drivers has the potential to substantially improve outcomes of cancer,” Goyal told Healio. “In addition, these data have encouraged us to continue to study futibatinib in patients whose tumors harbor other genomic abnormalities of FGFR, and a clinical trial program is underway.”
For more information:
Lipika Goyal, MD, can be reached at Stanford Cancer Center, 875 Blake Wilbur Drive, Palo Alto, CA 94304; email: lgoyal@stanford.edu.
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Goyal L, et al. N Engl J Med. 2023;doi:10.1056/NEJMoa2206834.
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