Multicenter phase 3 trial of trastuzumab rezetecan in ERBB2-low advanced breast cancer

Trastuzumab rezetecan has demonstrated encouraging antitumor activity in a phase 1 trial involving heavily pretreated patients with ERBB2-low metastatic breast cancer. The phase 3 HORIZON-Breast06 trial, at 73 centers in China, compared trastuzumab rezetecan versus physician’s choice of chemotherapy for adult patients who had received no more than one previous line of chemotherapy for ERBB2-low metastatic disease, with prior endocrine therapy required for hormone receptor-positive disease. Patients were randomized 1:1 to receive trastuzumab rezetecan 6.4 mg/kg every 2 weeks (n=277) or physician’s choice of chemotherapy (n=274). The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) in chemotherapy-naïve patients and the overall population. At the data cutoff, the median duration of follow-up was 15.5 months (IQR 9.7-21.5) months for all patients. Trastuzumab rezetecan significantly improved PFS compared with chemotherapy in the chemotherapy-naïve group (median 16.6 versus 6.8 months; HR 0.25; p<0.001) and in the overall population (median 16.4 versus 6.8 months; HR 0.27; p<0.001). The benefit was consistent in hormone receptor-negative and hormone receptor-positive disease. Grade 3 or greater treatment related adverse events occurred in 84.1% of patients with trastuzumab rezetecan and 67.9% of patients with chemotherapy. The authors conclude that trastuzumab rezetecan provided significant PFS benefit over physician’s choice of chemotherapy in patients with ERBB2-low advanced breast cancer, with benefit observed across all key subgroups (visual abstract).