On October 7, the U.S. Food and Drug Administration (FDA) approved tucatinib (Tukysa), a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab and pertuzumab for the maintenance treatment of adult patients with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.
HER2CLIMB-05
Efficacy was evaluated in 654 adult patients in HER2CLIMB-05 (ClinicalTrials.gov identifier NCT05132582), a randomized, 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 four to eight cycles of trastuzumab, pertuzumab, and a taxane. Patients received tucatinib at 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 by investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1; overall survival was an additional efficacy outcome measure. Median progression-free survival was 24.9 months (95% confidence interval [CI] = 21.3 months to not reached) in the tucatinib arm and 16.3 months (95% CI = 12.6–18.7 months) in the placebo arm (hazard ratio = 0.64, 95% CI = 0.51–0.80, P < .0001). At the time of the progression-free survival analysis, overall survival 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.
Recommended Dosage
The recommended tucatinib dosage is 300 mg orally twice daily in combination with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. Refer to the prescribing information of the combination agents for dosing and administration information.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
