FDA Approves Tucatinib Combo as Maintenance in HER2+ Breast Cancer

The FDA has approved tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta) as maintenance therapy for adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction therapy, according to a release from the agency.¹

Supporting findings for the approval came from the phase 3 HER2CLIMB-05 trial (NCT05132582) assessing tucatinib or placebo in combination with trastuzumab/pertuzumab among 654 adults with locally advanced or metastatic breast cancer that is HER2 positive. Topline data showed that the median progression-free survival per RECIST v1.1 criteria and investigator assessment was 24.9 months (95% CI, 21.3-not reached [NR]) with the tucatinib triplet vs 16.3 months (95% CI, 12.6-18.7) in the placebo arm (HR, 0.64; 95% CI, 0.51-0.80; P <.0001). The data for overall survival (OS), an additional efficacy end point, were not mature at the time of the analysis.

The prescribing information for the regimen includes a boxed warning for hepatotoxicity, and warnings and precautions for diarrhea, embryo-fetal toxicity, and increased serum creatinine without affecting renal function.

The agency approved tucatinib at a dose of 300 mg orally twice daily plus trastuzumab and pertuzumab until progressive disease or unacceptable toxicity.

“The treatment landscape for [HER2-positive] metastatic breast cancer has evolved dramatically over the past decade, but many patients still experience disease progression despite initial benefit from therapy,” principal investigator Erika Hamilton, MD, chief development officer and late phase & director of Breast Cancer Research for Sarah Cannon Research Institute (SCRI), stated in a press release regarding the approval.² “The HER2CLIMB-05 findings support [tucatinib] 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.”

References

1. FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer. News release. FDA. October 7, 2026. Accessed October 7, 2026. https://tinyurl.com/5c64mdtd
2. Pfizer’s TUKYSA regimen receives FDA approval as front-line maintenance treatment for HER2+ metastatic breast cancer. News release. Pfizer. October 7, 2026. Accessed October 7, 2026. https://tinyurl.com/yc32r5yn