futibatinib(福巴替尼)的功效与副作用？

Author: Medicalhalo

Release time: 2025-10-19 11:44:20

Futibatinib is a highly selective, irreversible FGFR1-4 inhibitor that can be used to treat cholangiocarcinoma, gastric cancer, urothelial cancer, esophageal cancer, non-small cell lung cancer and other cancers. However, patients may experience adverse reactions such as constipation, diarrhea, hyperphosphatemia, and fatigue during medication.

Efficacy

The FGFR signaling pathway is deregulated in many human cancers, and FGFR is considered an effective target in deregulated tumors. Among 296 human kinases, futibatinib selectively inhibits FGFR1-4 with IC50 values of 1.4 ~ 3.7 nmol/L. Futibatinib covalently binds to the FGFR kinase domain, thereby inhibiting FGFR phosphorylation and thereby inhibiting downstream signaling in tumor cell lines with dysregulated FGFR. Futibatinib has potent and selective growth inhibition against several tumor cell lines (gastric, lung, multiple myeloma, bladder, endometrium, and breast) harboring various FGFR genomic abnormalities. In various FGFR-driven human tumor xenograft models, oral futibatinib resulted in significant dose-dependent tumor reduction, and tumor reduction was associated with sustained FGFR inhibition and was proportional to the administered dose.

Futibatinib has a lower frequency of resistant clones than reversible ATP-competitive FGFR inhibitors, and futibatinib inhibits several drug-resistant FGFR2 mutations (including the FGFR2 V565I/L gatekeeper mutation) and is more potent than any reversible FGFR inhibitor tested (IC50, 1.3 ~ 50.6 nmol/L).

These results demonstrate that futibatinib is a novel, orally available, potent, selective, irreversible inhibitor of FGFR1-4 with broad-spectrum anti-tumor activity in cell lines and xenograft models.

medicine

1. Common adverse reactions: those with an incidence rate of greater than or equal to 20% include methamine, dry eyes, musculoskeletal pain, constipation, fatigue, joint pain, ataxia, diarrhea, dry mouth, vomiting, hair loss, urinary tract infection, loss of appetite, stomatitis, abdominal pain, dry skin, nausea, and palmar and plantar red sensation syndrome.

2. Common laboratory abnormalities: decreased hemoglobin, increased glucose, increased alanine aminotransferase, increased calcium, decreased platelets, increased phosphate, increased creatinine, decreased sodium, decreased phosphate, decreased albumin, decreased neutrophils, increased alkaline phosphatase, decreased lymphocytes, increased aspartate aminotransferase, increased activated partial thromboplastin time, increased bilirubin, increased international normalized prothrombin ratio, increased creatine kinase, decreased blood sugar, decreased potassium content, etc.

A study enrolling 197 patients with advanced solid tumors showed that futibatinib achieved an objective response rate (ORR) of 13.7% in a variety of tumors harboring known and previously uncharacterized FGFR1-3 abnormalities (cholangiocarcinoma and gastric cancer, urothelial cancer, central nervous system cancer, head and neck cancer, and breast cancer). The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients who previously developed acquired resistance to FGFR inhibitors also experienced remission after treatment with futibatinib.

Futibatinib demonstrated a manageable safety profile. The most common treatment-related adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results form the basis for the ongoing Phase 2/3 trial of futibatinib and demonstrate the potential for early-stage trials of genomic selection to help identify molecular subpopulations that may benefit from targeted therapies.

Significance: This phase I dose-expansion trial demonstrates the clinical activity and tolerability of the irreversible FGFR1-4 inhibitor futibatinib in multiple tumors with abnormal FGFR. These results form the rationale for ongoing Phase 2/3 trials of futibatinib in cholangiocarcinoma, breast cancer, gastroesophageal cancer and genomically selected disease-unknown populations.