Tucatinib: HER2 Inhibitor for Metastatic Breast Cancer
Tucatinib is a highly selective, small-molecule tyrosine kinase inhibitor targeting HER2 (ErbB2). Unlike other HER2-directed kinase inhibitors, tucatinib has minimal activity against the EGFR (HER1) receptor, which significantly reduces the incidence of skin and gastrointestinal toxicity.
The drug is used in combination with trastuzumab and capecitabine and has demonstrated notable efficacy in patients with brain metastases — a common and difficult-to-treat complication of HER2-positive breast cancer. On Unifarm, you can find details regarding original medications (such as Tukysa) containing this active ingredient.
Indications
- HER2-Positive Metastatic Breast Cancer: Treatment of adult patients with unresectable locally advanced or metastatic HER2-positive breast cancer (including patients with brain metastases) who have received one or more prior anti-HER2-based regimens in the metastatic setting.
- HER2-Positive Metastatic Colorectal Cancer: Treatment of adult patients with unresectable or metastatic HER2-positive colorectal cancer that has progressed following prior treatment (in combination with trastuzumab).
Dosage and administration
Available as tablets for oral administration.
Standard Regimen:
- Recommended Dose: 300 mg (two 150 mg tablets) taken orally twice daily approximately 12 hours apart.
- Administration: Swallow tablets whole with water. May be taken with or without food. Do not crush or break tablets.
- Combination: Used in combination with trastuzumab and capecitabine (breast cancer) or with trastuzumab (colorectal cancer).
Dose reductions to 250 mg, 200 mg, or 150 mg twice daily may be required for toxicity management. Regular hepatic function monitoring is essential. For moderate hepatic impairment (Child-Pugh B), the starting dose is reduced to 200 mg twice daily.
- Hypersensitivity to tucatinib or any component of the product.
- Pregnancy and breastfeeding (can cause fetal harm).
- Severe hepatic impairment (Child-Pugh C).
- Concomitant use with strong CYP3A inducers or strong CYP2C8 inhibitors (dose adjustment or avoidance required).
Tucatinib is typically used in combination regimens; therefore, adverse effects may be attributable to the entire treatment protocol. Common adverse reactions include:
- Gastrointestinal: Diarrhea (very common, can be severe), nausea, vomiting, stomatitis.
- Hepatic: Elevated transaminases (ALT, AST) and bilirubin — hepatotoxicity requiring regular monitoring.
- Dermatologic: Palmar-plantar erythrodysesthesia (related to capecitabine), rash.
- Hematologic: Anemia, neutropenia, thrombocytopenia.
- General: Fatigue, decreased appetite, weight loss.
- Musculoskeletal: Arthralgia, myalgia.
- Infections: Increased susceptibility to infections.
