Multinational phase 3 trial of trastuzumab duocarmazine for pretreated HER2-positive locally advanced or metastatic breast cancer

Trastuzumab duocarmazine (T-Duo) is a third-generation HER2-targeted antibody drug conjugate. The multinational phase 3 TULIP trial compared T-Duo versus physician’s choice (PC) for HER2-positive locally advanced or metastatic breast cancer with progression during or after 2 or more HER2-targeted therapies of after trastuzumab emtansine. The median PFS was 7.0 months with T-Duo versus 4.9 months with PC (HR 0.64; p=0.002). PFS benefit was maintained across most predefined subgroups. Grade ≥ 3 treatment-emergent adverse events occurred in 52% of patients with T-Duo and 48.2% with PC. Tolerability of T-Duo was affected by prevalent ocular toxicity, leading to a higher discontinuation rate in the T-Duo arm. The authors conclude that T-Duo significantly reduced the risk of progression in patients with advanced HER2-positive breast cancer who have progressed during or after previous HER2-targeted therapy.