Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study
| Autor: | Meric-Bernstam, Funda, Bahleda, Rastislav, Hierro, Cinta, Sanson, Marc, Bridgewater, John, Arkenau, Hendrik-Tobias, Tran, Ben, Kelley, Robin Kate, Park, Joon Oh, Javle, Milind, He, Yaohua, Benhadji, Karim A, Goyal, Lipika |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Maximum Tolerated Dose Fibroblast Growth Factor Prevention Clinical Trials and Supportive Activities Oncology and Carcinogenesis Evaluation of treatments and therapeutic interventions Antineoplastic Agents Middle Aged Disease-Free Survival Cholangiocarcinoma Pyrimidines Rare Diseases Bile Duct Neoplasms Clinical Research 6.1 Pharmaceuticals Breast Cancer Humans Pyrazoles Pyrroles Female Digestive Diseases Receptor Type 1 Cancer |
| Zdroj: | Cancer discovery, vol 12, iss 2 |
| Popis: | Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, was evaluated in a large multihistology phase I dose-expansion trial that enrolled 197 patients with advanced solid tumors. Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer) bearing both known and previously uncharacterized FGFR1-3 aberrations. The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients with acquired resistance to a prior FGFR inhibitor also experienced responses with futibatinib. Futibatinib demonstrated a manageable safety profile. The most common treatment-emergent adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy. SIGNIFICANCE: This phase I dose-expansion trial demonstrated clinical activity and tolerability of the irreversible FGFR1-4 inhibitor futibatinib across a broad spectrum of FGFR-aberrant tumors. These results formed the rationale for ongoing phase II/III futibatinib trials in cholangiocarcinoma, breast cancer, gastroesophageal cancer, and a genomically selected disease-agnostic population.This article is highlighted in the In This Issue feature, p. 275. |
| Databáze: | OpenAIRE |
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