Tucatinib

Tucatinib is a tyrosine kinase inhibitor (TKI) used in the treatment of HER2-positive metastatic breast cancer. Specifically, it is a highly selective and reversible inhibitor of the human epidermal growth factor receptor 2 (HER2) tyrosine kinase.

Mechanism of Action: Tucatinib works by binding to the ATP-binding pocket of the HER2 kinase, inhibiting its activity. This disrupts downstream signaling pathways involved in cell growth, proliferation, and survival. Its selectivity for HER2 over other kinases, such as EGFR, contributes to a potentially improved safety profile compared to less selective HER2 inhibitors.

Indications: Tucatinib is indicated, in combination with trastuzumab and capecitabine, for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer who have received prior anti-HER2-based regimens.

Administration: Tucatinib is administered orally, typically twice daily. It is usually given in combination with trastuzumab (an anti-HER2 monoclonal antibody) and capecitabine (a chemotherapy drug).

Adverse Effects: Common adverse effects associated with tucatinib include diarrhea, hand-foot syndrome (palmar-plantar erythrodysesthesia), fatigue, nausea, vomiting, stomatitis, decreased appetite, rash, and increased liver enzymes. Serious adverse effects may include hepatotoxicity.

Drug Interactions: Tucatinib is metabolized by CYP enzymes, and therefore may be subject to drug interactions with CYP inhibitors and inducers. Caution should be exercised when co-administering tucatinib with drugs that affect CYP enzyme activity.

Pharmacokinetics: Tucatinib is absorbed following oral administration and reaches peak plasma concentrations within a few hours. It is primarily metabolized by CYP3A4 and to a lesser extent by CYP2C8.