On October 7, 2026, Tukysa (tucatinib) in combination with trastuzumab and pertuzumab was approved by the FDA for maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.

Approval was based on efficacy and safety evaluations reported in HER2CLIMB-05, a randomized, double-blind, placebo-controlled trial in 654 patients. Eligible participants had HER2-positive, unresectable locally advanced or metastatic breast cancer, with or without brain metastases, and no evidence of disease progression determined by investigator assessment following induction treatment with 4 to 8 cycles of trastuzumab, pertuzumab, and a taxane. Results of this trial were presented at the 2025 San Antonio Breast Cancer Symposium.

Patients received tucatinib 300 mg or placebo either orally twice daily with trastuzumab and pertuzumab given intravenously or subcutaneously with a fixed-dose combination of trastuzumab, pertuzumab, and hyaluronidase. Patients with hormone receptor–positive disease continued their endocrine therapy. Treatment was continued until disease progression or unacceptable toxicity.

The primary efficacy outcome measure was progression-free survival (PFS) by investigator assessment using RECIST v1.1. At the time of PFS analysis, overall survival data were not mature.

Median PFS

• 24.9 months in the tucatinib arm (95% CI, 21.3, not reached)
• 16.3 months in the placebo arm (95% CI, 12.6-18.7)
• Hazard ratio, 0.64; 95% CI, 0.51-0.80; P<.0001

The recommended tucatinib dosage is 300 mg orally twice daily; trastuzumab and pertuzumab should be dosed and administered per their respective prescribing information.

The prescribing information for Tukysa 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.

Source

US Food and Drug Administration. FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer. October 7, 2026. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tucatinib-trastuzumab-and-pertuzumab-maintenance-treatment-her2-positive-breast-cancer