Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial.
Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial.
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DOI：
10.1038/s41422-023-00795-2
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发表时间：
2023-05
期刊：
影响因子：
44.1
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
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
三阴性乳腺癌（TNBC）是一种异质性疾病，缺乏有效的治疗方法。我们之前的研究将 TNBC 分为四种亚型，并具有假定的治疗靶点。在此，我们报告 FUTURE 的最终结果，这是一项 II 期伞式试验，旨在探讨基于亚型分型的策略是否可以改善转移性 TNBC 患者的预后。共有 141 名转移性患者接受过 3 种既往治疗，分为 7 个平行组。 42 名患者获得了确认的客观缓解（29.8%；95% 置信区间 [CI]，22.4–38.1）。无进展生存期和总生存期的中位值分别为 3.4 (95% CI: 2.7–4.2) 和 10.7 (95% CI: 9.1–12.3) 个月。考虑到贝叶斯预测概率，四个组均达到了功效边界。此外，综合基因组和临床病理学分析说明了临床和基因组参数与治疗效果的关联，并且在治疗无效的亚型的临床前 TNBC 模型中探索了新型抗体-药物缀合物的功效。总的来说，FUTURE 策略能够有效地招募患者，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。
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.
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