Tucatinib (also translated as Tukatinib; brand name: Tukysa, Everest)

Description
Product introduction:
Tucatinib (also translated as Tukatinib; brand name: Tukysa), produced by Everest, is a highly selective HER2-targeted inhibitor that can suppress the growth of HER2-overexpressing tumor cells.

In 2020, the U.S. FDA approved tucatinib in combination with trastuzumab and capecitabine for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have previously received one or more anti-HER2 therapies.

In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, thereby suppressing downstream MAPK and AKT signaling pathways and cell proliferation, demonstrating antitumor activity in HER2-expressing tumor cells. In vivo, tucatinib inhibits the growth of HER2-expressing tumors, and the combination of tucatinib and trastuzumab shows enhanced antitumor activity compared with either agent alone in both in vitro and in vivo models.

Indications:
Indicated in combination with trastuzumab and capecitabine for adult patients with HER2-positive breast cancer that is metastatic (including brain metastases) or unresectable, who have previously received one or more anti-HER2 therapies.

Dosage and administration:
The recommended dose is 300 mg orally twice daily in combination with trastuzumab and capecitabine, continued until disease progression or unacceptable toxicity.

Tukysa tablets should be swallowed whole; do not chew, crush, or split them. Do not take broken or incomplete tablets.

Doses should be taken approximately 12 hours apart. Tucatinib should be taken on an empty stomach.

When used in combination, the recommended dose of capecitabine is 1000 mg/m² twice daily, taken within 30 minutes after a meal. Tucatinib and capecitabine may be taken at the same time. Please refer to the full prescribing information for trastuzumab and capecitabine for additional details.

Adverse reactions:
Serious adverse effects include diarrhea, liver disease, pruritus, jaundice of the skin or eyes, dark urine, right upper abdominal pain, fatigue, decreased appetite, and easy bruising or bleeding.

Common adverse reactions include diarrhea, palmar-plantar erythrodysesthesia (hand-foot syndrome), pain, swelling or rash with blisters on palms or soles, oral ulcers, decreased appetite, abdominal pain, nausea, vomiting, fatigue, elevated liver function tests, headache, anemia, rash, and potential effects on fertility in both males and females.

Precautions:
Diarrhea: Tucatinib can cause severe diarrhea, potentially leading to dehydration, hypotension, acute kidney injury, and death. Diarrhea occurred in 81% of patients, including 12% grade 3 and 0.5% grade 4 cases. Antidiarrheal treatment should be administered as clinically indicated. Dose interruption, reduction, or permanent discontinuation may be required depending on severity.

Hepatotoxicity: Liver function tests (ALT, AST, and bilirubin) should be monitored every 3 weeks before and during treatment. Dose reduction or permanent discontinuation may be required depending on severity.

Embryo-fetal toxicity: Females of reproductive potential should use effective contraception during treatment. Male patients should also use effective contraception during treatment and for at least 1 week after the last dose.