This is the report of a phase 2 study assessing safety and efficacy of pemigatinib, a selective, oral inhibitor of FGFR1,2,3, in patients with previously treated advanced cholangiocarcinoma with and without FGFR2 fusions/rearrangements. 146 patients were enrolled: 107 with FGFR2 fusions/rearrangements, 20 with other FGF/FGFR alterations, 18 with no FGF/FGFR alterations, 1 with an undetermined FGF/FGFR alteration. The most common adverse event (AE) was hyperphosphatemia in 60% of the patients. Grade ≥3 AEs were observed in 64% of patients, hypophosphatemia 12%, arthralgia 6%, stomatitis, hyponatremia, abdominal pain, fatigue 5% each. Serious AEs occurred in 45% of the patients, abdominal pain and pyrexia 5% each, cholangitis and pleural effusion 3% each. No toxic deaths were reported. In patients with FGFR2 fusions/rearrangements objective response rate was 35.5%, disease control rate 82%, median progression free survival 6.9 months (95%CI 6.2-9.6), median overall survival 21.1 months (95%CI 14.8-NE). These data demonstrate the potential benefit of pemigatinib in patients with cholangiocarcinoma and FGFR2 fusions/rearrangements and a phase 3 trial is ongoing in first-line vs standard-of-care gemcitabine plus cisplatin chemotherapy (FIGHT-302).

(Abou-Alfa GK et al. – Lancet Oncol, 20 March 2020)

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