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

PURPOSE 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). METHODS 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. RESULTS 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. CONCLUSION 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.

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Journal
Journal of Clinical Oncology
Published
2026-09-11
DOI
https://doi.org/10.1200/jco-26-00602
Primary Topic
HER2/EGFR in Cancer Research
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article
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article

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

Haijun Yu, Jingfen Wang, Yongli Gao, Junyou Ge et al.
Journal of Clinical Oncology
HER2/EGFR in Cancer Research
article

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

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

Abstract

PURPOSE 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). METHODS 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. RESULTS 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. CONCLUSION 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.

Journal of Clinical Oncology
Target (United States) (US), Harbin Medical University (CN), Sun Yat-sen University (CN), Guangxi Medical University (CN), Dalian Medical University (CN), Anhui Medical University (CN), Tianjin Medical University Cancer Institute and Hospital (CN), Shantou University (CN), Wuhan University (CN), First Affiliated Hospital of Xiamen University (CN), Second People's Hospital of Yunnan Province (CN), Fudan University Shanghai Cancer Center (CN), Jiangxi Provincial Cancer Hospital (CN), Sun Yat-sen Memorial Hospital (CN), Linyi People's Hospital (CN), Jilin Province Tumor Hospital (CN), Zhejiang Cancer Hospital (CN), Shandong Tumor Hospital (CN), Second Affiliated Hospital of Dalian Medical University (CN), Third Affiliated Hospital of Harbin Medical University (CN), Yue Bei People's Hospital (CN), Weifang People's Hospital (CN), Third Hospital of Nanchang (CN), Hunan Cancer Hospital (CN), Sichuan Cancer Hospital (CN), Zhongnan Hospital of Wuhan University (CN), Second Hospital of Nanchang (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), Kelun Group (China) (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Second Affiliated Hospital of Xi'an Jiaotong University (CN), First Hospital of China Medical University (CN), Affiliated Hospital of Hebei University (CN), Sun Yat-sen University Cancer Center (CN), Fujian Provincial Cancer Hospital (CN), Second Affiliated Hospital of Anhui Medical University (CN), Chongqing Cancer Hospital (CN), First Affiliated Hospital of Zhengzhou University (CN), Hubei Cancer Hospital (CN), Liaoning Cancer Hospital & Institute (CN), Shandong First Medical University (CN), Pingjin Hospital (CN), Nanjing Medical University (CN), Chongqing Medical University (CN), China Medical University (CN)
Good health and well-being
Openalex Percentile: Top 14%
HER2/EGFR in Cancer Research
DOISourceOpenAlex
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