FDA Approves Tucatinib Plus Trastuzumab and Pertuzumab for Maintenance Treatment of HER2-Positive Advanced Breast Cancer
Clinical Summary:
- Regulatory Update: The FDA approved tucatinib in combination with trastuzumab and pertuzumab for maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.
- Key Outcomes: In HER2CLIMB-05, adding tucatinib to trastuzumab and pertuzumab significantly prolonged progression-free survival (PFS) compared with placebo plus trastuzumab and pertuzumab, reducing the risk of disease progression or death by 36%. Overall survival data were immature at the time of the PFS analysis.
- Clinical Relevance: The approval introduces tucatinib into the maintenance setting following first-line induction therapy, providing an additional HER2-targeted strategy for extending disease control in patients with advanced HER2-positive breast cancer, including those with brain metastases.
Based on results from the HER2CLIMB-05 trial, the US Food and Drug Administration (FDA) has approved tucatinib (Tukysa; Seagen) in combination with trastuzumab and pertuzumab for maintenance treatment of adult patients with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment.
In this double-blind, placebo-controlled trial, 654 patients with no evidence of disease progression following 4 to 8 cycles of induction treatment with trastuzumab, pertuzumab, and a taxane were randomized to receive either 300 mg of tucatinib or placebo twice daily in combination with intravenous trastuzumab and pertuzumab until disease progression or unacceptable toxicity. Trastuzumab and pertuzumab could alternatively be administered as a fixed-dose subcutaneous combination with hyaluronidase. Patients with hormone receptor–positive disease were permitted to continue endocrine therapy.
The primary end point was investigator-assessed progression-free survival (PFS), as assessed via RECIST version 1.1. A key secondary end point was overall survival (OS).
At analysis, median PFS was 24.9 months in the tucatinib plus trastuzumab and pertuzumab arm and 16.3 months in the placebo plus trastuzumab and pertuzumab arm. The addition of tucatinib reduced the risk of disease progression or death by 36% (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.51 to 0.80; P < .0001). OS data were not mature at the time of the PFS analysis.
The recommended tucatinib dose is 300 mg orally twice daily in combination with trastuzumab and pertuzumab until disease progression or unacceptable toxicity.
The prescribing information for tucatinib includes a boxed warning for hepatotoxicity. Additional warnings and precautions include 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. Accessed on: October 7, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tucatinib-trastuzumab-and-pertuzumab-maintenance-treatment-her2-positive-breast-cancer
