The US FDA has approved Pfizer's (NYSE: PFE) Tukysa (tucatinib) in combination with trastuzumab and pertuzumab for the maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer following induction treatment, as per a press release. The approval moves tucatinib into the front-line setting, extending its use beyond the second-line indication it has held since 2020, and offers a chemotherapy-free oral maintenance option, Pfizer said.
Tucatinib is an orally administered, reversible ATP-competitive tyrosine kinase inhibitor with substantially greater selectivity for HER2 than for EGFR, and it is given alongside trastuzumab and pertuzumab, which act on the extracellular domain of HER2.
The Phase III HER2CLIMB-05 trial randomized patients with HER2-positive metastatic breast cancer who completed induction therapy with trastuzumab, pertuzumab, and a taxane with no evidence of progression. The tucatinib arm achieved a median progression-free survival of 24.9 months versus 16.3 months in the placebo arm (hazard ratio 0.64; p<0.0001), as reported previously. The approved label carries a boxed warning for severe and fatal hepatotoxicity, particularly after rechallenge, requiring liver function monitoring before and during treatment.
The approval comes amid a changing first-line treatment landscape for HER2-positive metastatic breast cancer, following the December 2025 US FDA approval of AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) plus pertuzumab. While that regimen is used as initial systemic treatment, Tukysa's new indication covers maintenance following chemotherapy-based induction, placing the two approaches at different points in the first-line treatment pathway.