TUKYSA

What it is

TUKYSA contains tucatinib, a tyrosine kinase inhibitor of HER2. TUKYSA is available as film-coated tablets containing either 50 mg or 150 mg of tucatinib.

Approved indications

— Treatment of adult patients with RAS wild-type HER2 positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan based chemotherapy, in combination with trastuzumab. — Treatment of patients with advanced unresectable 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, in combination with trastuzumab and capecitabine.

Dosing overview

TUKYSA tablets should be swallowed whole, and not chewed, crushed, or split prior to swallowing. TUKYSA should be taken approximately 12 hours apart, at the same times every day, and can be taken with or without a meal.

Key safety warnings

TUKYSA can cause severe diarrhoea, leading to dehydration, hypotension, acute kidney injury and death. In the HER2CLIMB trial, 81% of patients who received TUKYSA experienced diarrhoea, including 12% with Grade 3 diarrhoea and 0.5% with Grade 4 diarrhoea. Both patients who developed Grade 4 diarrhoea subsequently died, with diarrhoea as a contributor to death. TUKYSA can cause severe hepatotoxicity. ALT, AST, and bilirubin should be assessed prior to starting TUKYSA, every three weeks during treatment, and as clinically indicated. Based on findings from animal studies and its mechanism of action, TUKYSA may cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of tucatinib to pregnant rats and rabbits during organogenesis caused embryo-fetal mortality, reduced fetal weight and fetal abnormalities at maternal exposures ≥1.3 times the human exposure (AUC) at the recommended dose. Females of reproductive potential should use effective contraception during treatment with TUKYSA and for at least 1 week after the last dose.

Contraindications

TUKYSA is contraindicated in patients with hypersensitivity to tucatinib or to any of the excipients.

Regulatory history

TUKYSA tucatinib 50 mg and 150 mg film-coated tablets were first listed on the Australian Register of Therapeutic Goods on 13 August 2020. In March 2021, the PBAC did not recommend TUKYSA for the treatment of HER2-positive metastatic breast cancer, including patients with brain metastases, in combination with trastuzumab and capecitabine. TUKYSA is subject to additional monitoring in Australia to allow quick identification of new safety information.