FDA approves Tukysa, frontline maintenance therapy for HER2-positive metastatic breast cancer

On October 7, 2026, FDA approved Tukysa (tucatinib) in combination with trastuzumab and pertuzumab for the maintenance treatment of adults with unresectable locally advanced or metastatic human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer following induction treatment.

The approval expands tucatinib into an earlier treatment setting for HER2-positive metastatic breast cancer. Until now, tucatinib was approved only after prior anti-HER2 treatment in the metastatic setting. The new indication adds tucatinib to maintenance therapy for patients whose disease has not progressed after initial treatment with trastuzumab, pertuzumab, and a taxane.

FDA's decision was supported by results from the phase 3 HER2CLIMB-05 trial, which enrolled patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases. Adding tucatinib to trastuzumab and pertuzumab reduced the risk of disease progression or death by 36% compared with trastuzumab and pertuzumab alone. Patients receiving the tucatinib regimen remained free from disease progression for a median of 24.9 months versus 16.3 months in the control group, extending median progression-free survival by more than eight months. Overall survival data are not yet mature.

The safety profile was generally consistent with previous tucatinib experience, although hepatotoxicity was more severe than previously reported. The prescribing information includes a boxed warning for hepatotoxicity and warnings for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function. The most common adverse reactions included diarrhea, musculoskeletal pain, hepatotoxicity, nausea, fatigue, rash, and vomiting. Serious hepatotoxicity occurred in 3.9% of patients, including one fatal case of drug-induced liver injury.

“The treatment landscape for HER2+ metastatic breast cancer has evolved dramatically over the past decade, but many patients still experience disease progression despite initial benefit from therapy," said principal investigator Erika Hamilton, MD, of Sarah Cannon Research Institute. "The HER2CLIMB-05 findings support TUKYSA plus trastuzumab and pertuzumab as a chemotherapy-free maintenance strategy that allows us to target HER2-positive tumors from multiple angles and can help prolong disease control.”

Sources: FDA. (2026 Oct 7). FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer; Pfizer. (2026 Oct 7). Pfizer’s TUKYSA Regimen Receives FDA Approval as Front-Line Maintenance Treatment for HER2+ Metastatic Breast Cancer