A median progression-free survival of 16.4 months set against just 6.8 months for standard chemotherapy. That is the striking margin delivered by trastuzumab rezetecan in HER2-low advanced breast cancer, according to phase 3 results presented at the European Society for Medical Oncology 2026 annual meeting.
The HORIZON-Breast06 Trial Data
The antibody-drug conjugate reduced the risk of disease progression or death by 73%. The HORIZON-Breast06 trial enrolled 551 women across 73 centers in China and met its primary endpoints for the overall population and chemotherapy-naive patients.
Among those who had not previously received chemotherapy for metastatic disease, the median progression-free survival reached 16.6 months with trastuzumab rezetecan compared with 6.8 months for physician’s choice of chemotherapy.
Published Findings and Response Rates
Simultaneously published in the Journal of the American Medical Association (JAMA), the study showed an objective response rate of 75.5% for the ADC. Standard chemotherapy achieved 41.2%.
While overall survival data remain immature, a descriptive analysis indicated a 12-month survival rate of 90.6% for the trastuzumab rezetecan group. Patients receiving chemotherapy recorded an 81.4% rate over the same timeframe.
Managing Hematologic Toxicity and Lung Risks
The survival benefit of the ADC was accompanied by higher rates of hematologic toxicity. Grade 3 or higher treatment-related adverse events were reported in 84.1% of patients receiving trastuzumab rezetecan, compared with 67.9% in the chemotherapy arm. Neutropenia was the most frequent severe event, occurring in 65.2% of the ADC group.
Interstitial lung disease (ILD), a known safety concern for HER2-directed ADCs, was observed in 2.5% of patients treated with trastuzumab rezetecan. None of these cases were fatal. In an accompanying editorial, Maria Fernanda Mosele, MD, and Fabrice André, MD, PhD, noted that this ILD incidence is lower than the 12% to 15% rate typically reported with trastuzumab deruxtecan (T-DXd) in similar settings.
Regulatory Status and Sequencing Challenges
Trastuzumab rezetecan is currently approved in China for several HER2-driven cancers but remains investigational for HER2-low breast cancer and is not yet approved in the United States or the European Union. Because both trastuzumab rezetecan and T-DXd target HER2 and utilize topoisomerase I inhibitor payloads, researchers are investigating whether overlapping resistance mechanisms could limit their sequential use.
Barbara Pistilli, MD, of Gustave Roussy, noted that while the new ADC features a modified payload and potentially enhanced membrane permeability, it remains unclear if these pharmacological differences translate into superior clinical outcomes compared to currently approved agents. Because no head-to-head trials exist, clinicians currently lack evidence to guide the optimal integration or sequencing of these competing therapies.
How Does Trastuzumab Rezetecan Compare to T-DXd?
How does trastuzumab rezetecan compare to T-DXd?
While both are HER2-targeted ADCs with similar clinical benefit ranges, they possess different pharmacological properties. Editorialists at Gustave Roussy noted that while trastuzumab rezetecan may have a lower incidence of ILD, it appears to carry higher risks for hematologic and hepatic toxicities in indirect comparisons.
What was the role of the APEX-Breast01 trial?
Presented during the same session as the HORIZON-Breast06 results, the APEX-Breast01 trial evaluated rolditamig deuderuxtecan (TQB2102), a biparatopic HER2-targeted ADC. It showed a median progression-free survival of 16.4 months versus 5.5 months for chemotherapy in patients with HER2-low recurrent or metastatic breast cancer.
What is the current regulatory status of these drugs?
Trastuzumab rezetecan is approved in China for HER2-positive advanced breast cancer but is not approved in the United States or the European Union for HER2-low breast cancer. Both agents presented at the 2026 ESMO meeting are part of a rapidly expanding field of HER2-targeted therapies currently undergoing clinical evaluation.
- Amgen’s Imdelltra Combined with Imfinzi Extends Lung Cancer Survival in Trial
- Nuria Oliver to receive honorary doctorate from University of Jaén
- Health Service to Explore AI for Breast Cancer Screening (archyworldys.com)
- Mum Diagnosed with Rare FATWO Cancer After Doctors Dismissed Symptoms as Perimenopause (news-usa.today)