The US Food and Drug Administration (FDA) has approved tucatinib (Tukysa, Seagen Inc., a subsidiary of Pfizer) in combination with trastuzumab and pertuzumab for the maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction.

Efficacy was evaluated in 654 adult patients in HER2CLIMB-05 (NCT05132582), a randomised, double-blind, placebo-controlled trial. Eligible patients were required to have HER2-positive, unresectable locally advanced or metastatic breast cancer, with or without brain metastases, and no evidence of disease progression by investigator assessment after induction treatment with 4-8 cycles of trastuzumab, pertuzumab, and a taxane.

Patients received tucatinib 300 mg or placebo orally twice daily with trastuzumab and pertuzumab intravenously, or with a fixed-dose combination of trastuzumab, pertuzumab, and hyaluronidase administered subcutaneously. Patients with hormone receptor positive disease were permitted to continue endocrine therapy. Patients were treated until disease progression or unacceptable toxicity.

The primary efficacy outcome measure was Progression-Free Survival (PFS) by investigator assessment using RECIST v1.1. The Overall Survival (OS) was an additional efficacy outcome measure. Median PFS was 24.9 months (95 percent CI: 21.3, not reached) in the tucatinib arm and 16.3 months (95 percent CI: 12.6, 18.7) in the placebo arm (Hazard Ratio 0.64 [95 percent CI: 0.51, 0.80]; p-value <0.0001). At the time of PFS analysis, OS data were not mature.

The prescribing information includes a boxed warning for hepatotoxicity, as well as warnings and precautions for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function.

The recommended tucatinib dosage is 300 mg orally twice daily in combination with trastuzumab and pertuzumab until disease progression or unacceptable toxicity.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.