Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial.

Authors

Jian Zhang, Quchang Ouyang, Qingyuan Zhang, Huihui Li, Xu Wang, Ying Wang, Yongmei Yin, Shusen Wang, Yuanting Gu, Tao Sun, Jingfen Wang, Xinhong Wu, Fanfan Li, Xi Chen, Man Li, Jin Yang, Hua Yang, Zhengkui Sun, Jianyun Nie, Xiaojia Wang, Jian Liu, Xianjun Tang, Hao Wang, Zhan Huang, Weimin Xie, Wenyan Chen, Fan Li, Yuee Teng, Shuqun Zhang, Ru Zeng, Wenhui Wang, Lixia Ma, Yongli Gao, Haijun Yu, Xiguang Cao, Yan Qing, Xiaoping Jin, Junyou Ge, Hongxia Wang, Xichun Hu

Published in

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Pages JCO2600602. Sep 11, 2026. Epub Sep 11, 2026.

Abstract

To evaluate the safety and efficacy of the novel human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate, trastuzumab botidotin, for the treatment of HER2-positive unresectable/metastatic breast cancer (BC).
In this phase III, open-label, multicenter trial (ClinicalTrials.gov identifier: NCT06968585), conducted at 57 centers in China, adult patients with HER2-positive, unresectable/metastatic BC who had received prior trastuzumab and a taxane were randomly assigned (1:1) to receive trastuzumab botidotin or trastuzumab emtansine. The primary end point was progression-free survival (PFS), assessed by blinded independent central review (BICR), using an intention-to-treat analysis. In a prespecified interim analysis of PFS per BICR, trastuzumab botidotin met the prespecified superiority boundary (P < .0001). We report here the prespecified final analysis of PFS.
Between July 18, 2023, and April 26, 2024, 365 patients were randomly assigned to trastuzumab botidotin (n = 182) or trastuzumab emtansine (n = 183). At data cutoff (median follow-up, 14.9 months), trastuzumab botidotin resulted in longer PFS than trastuzumab emtansine (median, 11.1 v 4.4 months; hazard ratio [HR], 0.39 [95% CI, 0.30 to 0.51]; nominal P < .0001). Benefit was consistent across subgroups, including those defined by prior lines of anti-HER2 therapy, prior pertuzumab or anti-HER2 tyrosine kinase inhibitors, and visceral metastases. The objective response rate was 76.9% (95% CI, 70.1 to 82.8) with trastuzumab botidotin and 53.0% (95% CI, 45.5 to 60.4) with trastuzumab emtansine. Overall survival data were immature (medians not reached in either group; HR, 0.62 [95% CI, 0.38 to 1.03]). Grade ≥3 treatment-emergent adverse events occurred in 127 (69.8%) and 116 (63.7%) patients in each group, respectively. Ocular treatment-related adverse events had a high incidence with trastuzumab botidotin; however, with a protocol-defined algorithm, most events generally recovered or resolved. Trastuzumab botidotin treatment had low incidences of pulmonary, hematologic, hepatic, and GI toxicities.
Among patients with HER2-positive advanced BC previously treated with trastuzumab and a taxane, trastuzumab botidotin resulted in significantly longer PFS than trastuzumab emtansine, with a distinct safety profile.

PMID:
42727044
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

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