FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer
Regulatory approval: On Oct 7, 2026, the FDA approved tucatinib (Tukysa) plus trastuzumab and pertuzumab as maintenance therapy for adults with unresectable locally advanced or metastatic HER2-positive breast cancer without progression after induction with trastuzumab/pertuzumab and a taxane. Approval was supported by HER2CLIMB-05 (N=654), showing investigator-assessed PFS improvement (median 24.9 vs 16.3 months; HR 0.64; p<0.0001). OS data were not mature at the time of PFS analysis.
FDA approval (Oct 7, 2026)
The FDA 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 therapy.
Supporting evidence: HER2CLIMB-05 (NCT05132582)
Approval was based on HER2CLIMB-05, a randomized, double-blind, placebo-controlled trial in 654 adults with HER2-positive unresectable locally advanced or metastatic breast cancer with or without brain metastases, who had no investigator-assessed progression after 4–8 cycles of induction trastuzumab + pertuzumab + a taxane.
Patients received tucatinib 300 mg orally twice daily or placebo, with trastuzumab and pertuzumab given intravenously or via a fixed-dose subcutaneous combination (trastuzumab/pertuzumab/hyaluronidase). Patients with hormone receptor–positive disease could continue endocrine therapy. Treatment continued until progression or unacceptable toxicity.
Efficacy
Primary endpoint: PFS by investigator assessment (RECIST v1.1).
- Median PFS: 24.9 months (95% CI, 21.3–not reached) with tucatinib vs 16.3 months (95% CI, 12.6–18.7) with placebo; HR 0.64 (95% CI, 0.51–0.80); p<0.0001.
- OS was an additional endpoint; data were not mature at the time of PFS analysis.
Safety and dosing highlights
Labeling includes a boxed warning for hepatotoxicity, and warnings/precautions for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function. Recommended dose: tucatinib 300 mg PO BID with trastuzumab and pertuzumab until progression or unacceptable toxicity.