Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial.
Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial.
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分子亚型分析和基因组分析拓展了难治性转移性三阴性乳腺癌的精准医疗：FUTURE 试验
DOI：
10.1038/s41422-020-0375-9
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发表时间：
2021-03
期刊：
影响因子：
44.1
通讯作者：
Shao ZM
中科院分区：
文献类型：
--
作者：
Jiang YZ;Liu Y;Xiao Y;Hu X;Jiang L;Zuo WJ;Ma D;Ding J;Zhu X;Zou J;Verschraegen C;Stover DG;Kaklamani V;Wang ZH;Shao ZM
三阴性乳腺癌(TNBC)是一种高度异质性的疾病，分子分型可能会提高诊断的准确性和靶向治疗。我们先前的研究根据假定的治疗靶点将TNBCs分为四种亚型。在这里，我们进行了未来试验(ClinicalTrials.gov标识符：NCT03805399)，这是一项基于Ib/II期亚型和基因组生物标记物指导的伞式试验，以评估这些靶点的疗效。难治性转移性TNBC患者按TNBC亚型和基因组生物标志物进行分层，分为7组：(A)吡罗替尼联合卡培他滨，(B)雄激素受体抑制剂联合CDK4/6抑制剂，(C)抗PD-1联合NAB-紫杉醇，(D)PARP抑制剂，(E)和(F)抗VEGFR，或(G)mTOR抑制剂联合NAB-紫杉醇。主要终点为客观有效率(ORR)。我们招募了69名难治性转移性TNBC患者，中位数为之前的三个治疗路线(范围1-8)。在69例意向治疗(ITT)患者中，有20例(29.0%，95%可信区间：18.7%-41.2%)获得了客观有效。我们的结果显示，免疫治疗(ARM C)在ITT人群中获得了最高的ORR(52.6%，95%CI：28.9%-75.6%)。ARM E显示良好的ORR(26.1%，95%CI：10.2%-48.4%)，但有更多的高级别(≥3)不良事件。TOP2A和CD8免疫组织化学评分的体细胞突变有可能预测免疫调节亚型TNBC的免疫治疗反应。总之，Ib/II期未来试验为TNBC的治疗提出了一个新的概念，证明了基于亚型的靶向治疗难治性转移性TNBC的临床益处。
Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, and molecular subtyping may result in improved diagnostic precision and targeted therapies. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we conducted the FUTURE trial (ClinicalTrials.gov identifier: NCT03805399), a phase Ib/II subtyping-based and genomic biomarker-guided umbrella trial, to evaluate the efficacy of these targets. Patients with refractory metastatic TNBC were enrolled and stratified by TNBC subtypes and genomic biomarkers, and assigned to one of these seven arms: (A) pyrotinib with capecitabine, (B) androgen receptor inhibitor with CDK4/6 inhibitor, (C) anti PD-1 with nab-paclitaxel, (D) PARP inhibitor included, (E) and (F) anti-VEGFR included, or (G) mTOR inhibitor with nab-paclitaxel. The primary end point was the objective response rate (ORR). We enrolled 69 refractory metastatic TNBC patients with a median of three previous lines of therapy (range, 1–8). Objective response was achieved in 20 (29.0%, 95% confidence interval (CI): 18.7%–41.2%) of the 69 intention-to-treat (ITT) patients. Our results showed that immunotherapy (arm C), in particular, achieved the highest ORR (52.6%, 95% CI: 28.9%–75.6%) in the ITT population. Arm E demonstrated favorable ORR (26.1%, 95% CI: 10.2%–48.4% in the ITT population) but with more high grade (≥ 3) adverse events. Somatic mutations ofTOP2Aand CD8 immunohistochemical score may have the potential to predict immunotherapy response in the immunomodulatory subtype of TNBC. In conclusion, the phase Ib/II FUTURE trial suggested a new concept for TNBC treatment, demonstrating the clinical benefit of subtyping-based targeted therapy for refractory metastatic TNBC.
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三阴性乳腺癌的基因组和转录组景观：亚型和治疗策略
影响因子：
50.3
作者：
Jiang, Yi-Zhou;Ma, Ding;Shao, Zhi-Ming
通讯作者：
Shao, Zhi-Ming
DOI：
10.1158/1078-0432.ccr-13-3473
发表时间：
2015-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Herbst RS;Gandara DR;Hirsch FR;Redman MW;LeBlanc M;Mack PC;Schwartz LH;Vokes E;Ramalingam SS;Bradley JD;Sparks D;Zhou Y;Miwa C;Miller VA;Yelensky R;Li Y;Allen JD;Sigal EV;Wholley D;Sigman CC;Blumenthal GM;Malik S;Kelloff GJ;Abrams JS;Blanke CD;Papadimitrakopoulou VA
通讯作者：
Papadimitrakopoulou VA
影响因子：
45.3
作者：
Fong, Peter C.;Yap, Timothy A.;Kaye, Stan B.
通讯作者：
Kaye, Stan B.
影响因子：
45.3
作者：
Bardia, Aditya;Mayer, Ingrid A.;Vahdat, Linda T.
通讯作者：
Vahdat, Linda T.
影响因子：
168.9
作者：
Denkert, Carsten;Liedtke, Cornelia;von Minckwitz, Gunter
通讯作者：
von Minckwitz, Gunter