Trastuzumab rezetecan (SHR-A1811) more than doubled progression-free survival versus physician’s choice chemotherapy in patients with HER2-low advanced breast cancer in results from the Phase 3 HORIZON-Breast06 trial. Findings were presented at the European Society for Medical Oncology Congress 2026 and published simultaneously in JAMA. In chemotherapy-naïve patients, median PFS was 16.6 months with trastuzumab rezetecan versus 6.8 months with physician’s choice (hazard ratio 0.25; P<.001). The benefit held in the overall population as well (median PFS 16.4 vs 6.8 months; HR 0.27; P<.001), with subgroup analyses favoring the ADC across prespecified categories. Overall survival data remain immature, though results trended in favor of trastuzumab rezetecan. The program’s sponsor underscored the PFS separation across HR status, while commentators noted head-to-head comparisons against approved ADCs are still lacking.