FDA approves TUKYSA regimen as front-line maintenance treatment for HER2-positive metastatic breast cancer

Pfizer has received U.S. Food and Drug Administration approval for TUKYSA, also known as tucatinib, in combination with trastuzumab and pertuzumab as maintenance treatment for adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction therapy.

The decision expands the use of TUKYSA into the front-line metastatic setting and provides a chemotherapy-free maintenance option for eligible patients.

Approval was supported by results from the Phase III HER2CLIMB-05 study.

The trial compared TUKYSA plus trastuzumab and pertuzumab with placebo plus trastuzumab and pertuzumab following induction treatment.

The primary analysis showed that the TUKYSA regimen reduced the risk of disease progression or death by 35.9% compared with the control group.

The hazard ratio was 0.64, with a 95% confidence interval of 0.51 to 0.80 and a two-sided p value below 0.0001.

Median investigator-assessed progression-free survival reached 24.9 months in the TUKYSA group compared with 16.3 months in the placebo group.

This represented an 8.6 month improvement in the time patients lived without their disease worsening.

Aamir Malik, Executive Vice President and Chief U.S. Commercial Officer at Pfizer, said the approval moves TUKYSA into an earlier stage of metastatic breast cancer treatment.

He said the regimen offers patients a chemotherapy-free maintenance approach after initial treatment.

Erika Hamilton, MD, Principal Investigator of HER2CLIMB-05 and Chief Development Officer of Late Phase and Director of Breast Cancer Research at Sarah Cannon Research Institute, said the findings support targeting HER2-positive disease through multiple mechanisms while extending disease control.

The safety and tolerability profile of TUKYSA was generally consistent with its established profile, although increased severity of hepatotoxicity was observed.

Pfizer said most hepatotoxicity events were asymptomatic and reversible following dose modification or treatment discontinuation.

The most frequently reported adverse events, occurring in at least 20% of patients, included diarrhoea, musculoskeletal pain, hepatotoxicity, nausea, fatigue, rash and vomiting.

Serious adverse reactions occurring in at least 1% of patients included hepatotoxicity, which was reported in 3.9% of patients.

One patient experienced a fatal case of drug-induced liver injury.

Results from HER2CLIMB-05 were previously published in the Journal of Clinical Oncology and presented at the 2025 San Antonio Breast Cancer Symposium.

TUKYSA was initially approved in 2020 and has previously been used in later-line HER2-positive metastatic breast cancer.

The expanded indication now allows the treatment to be used as part of a front-line maintenance regimen following induction therapy.

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