Markus Eckstein, Senior Physician/Pathologist and Clinician Scientist at the University Hospital Erlangen, shared a post by on X:
“New in The Lancet Oncology: HORIZON-Breast01, a phase 3 interim analysis (very uncommon).
Trastuzumab rezetecan (SHR-A1811), a HER2-directed antibody-drug conjugate with a topoisomerase I inhibitor payload, beat pyrotinib plus capecitabine in HER2-positive metastatic breast cancer after prior trastuzumab and a taxane.
The numbers (4.8 mg/kg, n=142 vs control n=145):
- Median PFS 30.6 months vs 8.3 months. HR 0.22 (95% CI 0.15–0.34), p<0.0001.
- 12-month PFS 84.7% vs 35.5%.
- ORR 81.7% vs 55.9%. Median duration of response 27.8 vs 10.9 months.
- OS still immature (median not reached), but 12-month OS 96.3% vs 88.4%, HR 0.31, p=0.0012.
Safety: mostly haematologic. Grade ≥3 TRAEs 70% vs 63%. Interstitial lung disease in 4 patients (3%), no grade 4 or 5 events, exposure-adjusted rate 2.5% per patient-year. That ILD signal is low for a HER2 ADC and worth watching.
Caveats worth stating plainly. Interim analysis, so the PFS estimate may still shift. All 287 patients were enrolled at 50 Chinese sites. No head-to-head against trastuzumab deruxtecan, the current global standard. Funded by Jiangsu Hengrui.
Bottom line: a potential practice-changing option in this setting, pending mature OS and broader populations.”
Title: Trastuzumab rezetecan versus pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer (HORIZON-Breast01): interim analysis of a multicentre, open-label, randomised, controlled, phase 3 trial
Authors: Herui Yao, Qingyuan Zhang, Huiping Li, Yongmei Yin, Shusen Wang, Quchang Ouyang, Tao Sun, Wei Li, Xiaojia Wang, Min Yan, Biyun Wang, Jing Cheng, Zhongsheng Tong, Wei Wei, Xinshuai Wang, Weimin Xie, Zhengkui Sun, Peng Yuan, Cuizhi Geng, Lu Gan, Xinghua Han, Wenfeng Li, Shoubing Zhou, Xi Yan, Jinnan Gao, Tienan Yi, Jingna Wu, Zhaofeng Niu, Fangmeng Fu, Jianyun Nie, Yongsheng Wang, Bing Zhao, Zhiyong Wu, Zhengqiu Zhu, Yaping Yang, Jianli Zhao, Zhen Sheng, Ying Zhang, Lin Cheng, Xiaoyu Zhu, Erwei Song
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