Anbenitamab plus HB1801 for HER2-Positive Advanced Breast Cancer.

The combination of docetaxel, trastuzumab, and pertuzumab (THP) is an established first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. The efficacy and safety of anbenitamab, a HER2-targeted bispecific antibody, plus albumin-bound docetaxel (HB1801) in this context are unknown. In this phase 3, multicenter, open-label, randomized trial conducted in China, we randomly assigned patients with HER2-positive advanced breast cancer in a 1:1 ratio to receive either anbenitamab plus HB1801 or THP. The primary end point was progression-free survival, as assessed by blinded independent central review. Objective response was a secondary end point. A total of 885 patients were enrolled (445 were assigned to receive anbenitamab plus HB1801 and 440 to receive THP). At this prespecified interim analysis (with 401 events [disease progression or death] and a median follow-up of 21.0 months), the estimated 24-month progression-free survival was significantly higher with anbenitamab plus HB1801 than with THP (58.5% vs. 34.4%; hazard ratio for progression or death, 0.46; 95% confidence interval, 0.37 to 0.56; P<0.001). The percentage of patients with an objective response was 87.6% in the anbenitamab group and 73.4% in the THP group. Adverse events of grade 3 or higher occurred in 204 of 444 patients (45.9%) in the anbenitamab group and in 151 of 439 patients (34.4%) in the THP group. Neutropenia was the most common adverse event of grade 3 or higher in both groups (13.1% in the anbenitamab group and 8.4% in the THP group). Adverse events leading to death occurred in 2 patients in each group. Anbenitamab plus HB1801 led to significantly higher progression-free survival than THP among patients with HER2-positive advanced breast cancer. (Funded by Shanghai JMT-Bio Technology and others; HEALER ClinicalTrials.gov number, NCT05838066.).