The US Food and Drug Administration (FDA) has approved Pfizer’s TUKYSA (tucatinib), in combination with trastuzumab and pertuzumab, for the maintenance treatment of adults with unresectable, locally advanced or metastatic HER2-positive (HER2+) breast cancer following induction treatment.
The approval expands the use of TUKYSA into the frontline maintenance setting, providing a chemotherapy-free treatment option to delay disease progression.
The decision is based on results from the Phase 3 HER2CLIMB-05 trial, which evaluated TUKYSA plus trastuzumab and pertuzumab against placebo plus trastuzumab and pertuzumab as maintenance therapy in patients with HER2+ metastatic breast cancer following frontline induction treatment.
The primary analysis showed that the TUKYSA-based regimen reduced the risk of disease progression or death by 35.9% compared with the placebo regimen.
Median investigator-assessed progression-free survival (PFS) was 24.9 months in the TUKYSA arm, compared with 16.3 months in the placebo arm — an 8.6-month difference.
Aamir Malik, executive vice president and chief US commercial officer, Pfizer, said, “Since its first approval in 2020, TUKYSA has become an important treatment for patients with second-line HER2+ metastatic breast cancer. Today’s FDA approval marks the next chapter for TUKYSA, bringing it into the front-line maintenance setting and offering patients a chemotherapy-free option that can help delay disease progression after initial treatment.”
Erika Hamilton, principal investigator of HER2CLIMB-05 and chief development officer, Late Phase and director, Breast Cancer Research at Sarah Cannon Research Institute (SCRI), said while the treatment landscape for HER2+ metastatic breast cancer has evolved dramatically over the past decade, many patients still experience disease progression despite initial benefit from therapy.
“The HER2CLIMB-05 findings support TUKYSA plus trastuzumab and pertuzumab as a chemotherapy-free maintenance strategy that allows us to target HER2-positive tumours from multiple angles and can help prolong disease control,” she said.
Results from HER2CLIMB-05 were published in the Journal of Clinical Oncology and presented at the 2025 San Antonio Breast Cancer Symposium (SABCS).
TUKYSA (tucatinib) is an orally administered tyrosine kinase inhibitor of HER2. It is also approved in combination with trastuzumab and capecitabine for adults with HER2-positive, unresectable locally advanced or metastatic breast cancer, including patients with brain metastases who have received one or more prior anti-HER2 treatments in the metastatic setting.
