Trastuzumab Rezetecan Extends Progression-Free Survival in ERBB2-Low Advanced Breast Cancer

Trastuzumab rezetecan substantially prolonged progression-free survival (PFS) compared with physician-choice chemotherapy in patients with ERBB2 (HER2)-low advanced breast cancer who had received no more than 1 prior line of chemotherapy for metastatic disease, according to results of the phase 3 HORIZON-Breast06 randomized clinical trial published in JAMA.

The open-label trial, sponsored by Jiangsu Hengrui Pharmaceuticals, enrolled 551 women at 73 hospitals in China and included hormone receptor (HR)-positive and HR-negative disease. Patients with HR-positive disease were required to have received prior endocrine therapy. The dual primary endpoint was PFS by blinded independent central review in chemotherapy-naive patients and the overall population.

Among patients who had not received chemotherapy for advanced disease, median PFS was 16.6 months with trastuzumab rezetecan and 6.8 months with chemotherapy, corresponding to a hazard ratio of 0.25. In the overall population, median PFS was 16.4 months and 6.8 months, respectively, with a hazard ratio of 0.27. In exploratory analyses, benefit was observed across HR groups. Median PFS was 16.4 months with the antibody-drug conjugate versus 6.7 months with chemotherapy in HR-positive disease and 16.5 months versus 6.8 months in HR-negative disease. The objective response rate was 75.5% with trastuzumab rezetecan and 41.2% with chemotherapy.

Toxicity, particularly hematologic, was higher with trastuzumab rezetecan. Grade 3 or higher treatment-related adverse events occurred in 84.1% of patients receiving trastuzumab rezetecan and 67.9% receiving chemotherapy. Serious treatment-related events occurred in 37.7% and 13.7%, respectively, and interstitial lung disease was reported in 2.5% of patients receiving trastuzumab rezetecan. The investigators reported that hematologic toxicity frequently led to dose modification but was generally manageable with proactive management.

Overall survival data were immature at the analysis, and follow-up is ongoing. The investigators said the hazard ratio of 0.25 indicated a marked improvement over chemotherapy. They added that heterogeneous control regimens and evolving treatment standards warranted further validation against contemporary comparators, and they called for multinational trials to confirm generalizability.

Source: Fan Y, Liu Y, Wang Y, et al. Trastuzumab rezetecan in ERBB2-low advanced breast cancer: the HORIZON-Breast06 randomized clinical trial. JAMA. Published online October 23, 2026. doi:10.1001/jama.2026.21372