Futibatinib

Breast Feeding; Lactation; Milk, Human; Enzyme Inhibitors; Protein Kinase Inhibitors; Signal Transduction Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

In the open label clinical trials of futibatinib, adverse events were common and led to dose interruptions in 66%, dose reductions in 58%, and drug discontinuation in 5% of patients but only a small proportion of these were due to serum aminotransferase elevations. In preregistration trials in 103 patients with cholangiocarcinoma, ALT elevations arose in 50% and to above 5 times ULN in 7%. The elevations were typically self-limited and resolved rapidly with or without dose adjustments. No patients developed clinically apparent liver injury or jaundice. Publications on the efficacy and safety of futibatinib rarely mentioned serum ALT elevations or hepatotoxicity. Since its approval, there have been no reports clinically apparent liver injury attributed to futibatinib. However, the total clinical experience with its use has been limited and the frequency of serum aminotransferase elevations during therapy suggest that clinically significant liver injury may occur.

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Futibatinib is an anticancer agent with demonstrated anti-tumour activity in mouse and rat xenograft models of human tumours with activating FGFR genetic alterations. Futibatinib is not expected to affect cell lines with no FGFR genomic aberrations. It suppresses the growth of tumours in a dose-dependent manner.

Fibroblast Growth Factor receptor (FGFR) pathway play a key role in cell proliferation, differentiation, migration, and survival. Notably, FGFR genomic aberrations and aberrant FGFR signalling pathways are observed in some cancers, as constitutive FGFR signalling can support the proliferation and survival of malignant cells. Futibatinib is a selective, irreversible inhibitor of FGFR 1, 2, 3, and 4 with IC₅₀ values of less than 4 nM. It binds to the FGFR kinase domain by forming a covalent bond with cysteine in the ATP-binding pocket. Upon binding to FGFR, futibatinib blocks FGFR phosphorylation and downstream signalling pathways, such as the RAS-dependent mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3KCA)/Akt/mTOR, phospholipase Cγ (PLCγ), and JAK/STAT. Futibatinib ultimately decreases cell viability in cancer cell lines with FGFR alterations, including FGFR fusions or rearrangements, amplifications, and mutations.