复旦大学Zhi-Ming Shao和Zhong-Hua Wang共同合作，近期取得重要工作进展。他们研究报告了基于亚型的平台指导针对接受过多次治疗的转移性三阴性乳腺癌的精准医学，即FUTURE II期伞型临床试验。相关研究成果2023年3月27日在线发表于《细胞—研究》杂志上。

据介绍，三阴性乳腺癌（TNBC）是一种异质性疾病，缺乏有效治疗的方法。之前的研究将TNBC分为四种亚型，具有假定的治疗靶点。

研究人员报告了FUTURE的最终结果，这是一项II期伞式临床试验，旨在探索基于分型的策略是否可以改善转移性TNBC患者的预后。共有141名患者在转移性环境中接受了三种先前疗法的中位数，他们被纳入了七个平行组。42名患者（29.8%；95%置信区间[CI]，22.4–38.1）获得了确认的客观疗效。无进展生存期和总生存期的中位值分别为3.4个月（95%CI:2.7–4.2）和10.7个月（95%CI:9.1–12.3）。在给定贝叶斯预测概率的情况下，在四个组中达到了疗效边界。

此外，综合基因组和临床病理图谱显示了临床和基因组参数与治疗效果的相关性，并在治疗无效的亚型的临床前TNBC模型中探索了新型抗体-药物偶联物的疗效。

总的来说，FUTURE策略有效地招募患者，并提供有希望的疗效和可控的毒性，为进一步的临床探索指明了方向。

附：英文原文

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

Author: Liu, Yin, Zhu, Xiu-Zhi, Xiao, Yi, Wu, Song-Yang, Zuo, Wen-Jia, Yu, Qiang, Cao, A-Yong, Li, Jun-Jie, Yu, Ke-Da, Liu, Guang-Yu, Wu, Jiong, Sun, Tao, Cui, Jiu-Wei, Lv, Zheng, Li, Hui-Ping, Zhu, Xiao-Yu, Jiang, Yi-Zhou, Wang, Zhong-Hua, Shao, Zhi-Ming

Issue&Volume: 2023-03-27

Abstract: 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.

DOI: 10.1038/s41422-023-00795-2

Source: https://www.nature.com/articles/s41422-023-00795-2