Volume 33, No 5, May 2023

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 33 Issue 5, May 2023: 389-402   |  Open Access

ORIGINAL ARTICLES

Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial

Yin Liu^1,2,† , Xiu-Zhi Zhu^1,2,† , Yi Xiao^1,2,† , Song-Yang Wu^1,2,† , Wen-Jia Zuo^1,2 , Qiang Yu^1,2 , A-Yong Cao^1,2 , Jun-Jie Li^1,2 , Ke-Da Yu^1,2 , Guang-Yu Liu^1,2 , Jiong Wu^1,2 , Tao Sun³ , Jiu-Wei Cui⁴ , Zheng Lv⁴ , Hui-Ping Li⁵ , Xiao-Yu Zhu⁶ , Yi-Zhou Jiang^1,2,* , Zhong-Hua Wang^1,2,* , Zhi-Ming Shao^1,2,*

¹Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
²Key Laboratory of Breast Cancer in Shanghai, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
³Department of Medical Oncology, Cancer Hospital of China Medical University/Liaoning Cancer Hospital, Shenyang, Liaoning, China
⁴Department of Medical Oncology, First Hospital of Jilin University, Changchun, Jilin, China
⁵Department of Breast Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
⁶Jiangsu Hengrui Pharmaceuticals Co. Ltd, Shanghai, China
^†These authors contributed equally: Yin Liu, Xiu-Zhi Zhu, Yi Xiao, Song-Yang Wu
Correspondence: Yi-Zhou Jiang(yizhoujiang@fudan.edu.cn)Zhong-Hua Wang(zhonghuawang95@hotmail.com)Zhi-Ming Shao(zhimingshao@fudan.edu.cn)

Triple-negative breast cancer (TNBC) is a heterogeneous disease and lacks effective treatment. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we report the final results of FUTURE, a phase II umbrella trial designed to explore whether the subtyping-based strategy may improve the outcomes in metastatic TNBC patients. A total of 141 patients with a median of three previous lines of therapies in the metastatic setting were enrolled in seven parallel arms. Confirmed objective responses were achieved in 42 patients (29.8%; 95% confidence interval [CI], 22.4–38.1). The median values of progression-free survival and overall survival were 3.4 (95% CI: 2.7–4.2) and 10.7 (95% CI: 9.1–12.3) months, respectively. Given Bayesian predictive probability, efficacy boundaries were achieved in four arms. Furthermore, integrated genomic and clinicopathological profiling illustrated associations of clinical and genomic parameters with treatment efficacy, and the efficacy of novel antibody–drug conjugates was explored in preclinical TNBC models of subtypes for which treatment was futile. In general, the FUTURE strategy recruits patients efficiently and provides promising efficacy with manageable toxicities, outlining a direction for further clinical exploration.

https://doi.org/10.1038/s41422-023-00795-2

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