Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.
Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer.
复制标题
乳腺癌治疗veliparib-钙铂治疗的自适应随机化。
DOI：
10.1056/nejmoa1513749
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发表时间：
2016-07-07
期刊：
影响因子：
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通讯作者：
I-SPY 2 Investigators
中科院分区：
文献类型：
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作者：
Rugo HS;Olopade OI;DeMichele A;Yau C;van 't Veer LJ;Buxton MB;Hogarth M;Hylton NM;Paoloni M;Perlmutter J;Symmans WF;Yee D;Chien AJ;Wallace AM;Kaplan HG;Boughey JC;Haddad TC;Albain KS;Liu MC;Isaacs C;Khan QJ;Lang JE;Viscusi RK;Pusztai L;Moulder SL;Chui SY;Kemmer KA;Elias AD;Edmiston KK;Euhus DM;Haley BB;Nanda R;Northfelt DW;Tripathy D;Wood WC;Ewing C;Schwab R;Lyandres J;Davis SE;Hirst GL;Sanil A;Berry DA;Esserman LJ;I-SPY 2 Investigators
I-SPY 2是一项II期常设多中心平台试验，旨在筛选与标准新辅助化疗联合治疗乳腺癌的多种实验方案。目标是使实验方案与有反应的患者亚型相匹配。我们报告了维利帕尼（一种聚（ADP-核糖）聚合酶（PARP）抑制剂）与卡铂（VC）联合治疗的结果。符合条件的女性患有≥2.5 cm的II/III期乳腺癌，根据HER 2、受体状态（HR）和MammaPrint分为8种生物标志物亚型。与标准治疗（对照）相比，患者在亚型内适应性随机分配至性能更好的方案。方案在10个特征内进行评价，这些特征是前瞻性定义的亚型组合。对于HER 2阴性肿瘤，考虑VC加标准治疗，因此在3个特征中进行评价。I-SPY 2的主要终点是病理完全缓解（pCR）。治疗期间的MR体积变化告知患者将实现pCR的可能性。如果方案在随后的3期新辅助治疗试验中具有高（贝叶斯）预测成功概率，则方案在毕业签名内毕业。VC在三阴性乳腺癌中毕业，3期成功的预测概率为88%。共有72例患者随机分配至VC组，44例患者随机分配至同期对照组。相应的pCR估计值（95%概率区间）分别为51%（35%-69%）和26%（11%-40%）。VC的较大毒性是可控的。I-SPY 2的设计有可能有效地识别正在评估的各种疗法的响应肿瘤亚型。VC添加到标准治疗中可以提高三阴性乳腺癌的pCR率。
I-SPY 2 is a phase 2 standing multicenter platform trial designed to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to matching experimental regimens with responding patient subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin (VC). Eligible women had ≥2.5 cm stage II/III breast cancer, categorized into 8 biomarker subtypes based on HER2, hormone-receptor status (HR) and MammaPrint. Patients are adaptively randomized within subtype to better performing regimens compared to standard therapy (control). Regimens are evaluated within 10 signatures, prospectively defined combinations of subtypes. VC plus standard therapy was considered for HER2-negative tumors and therefore evaluated in 3 signatures. The primary endpoint of I-SPY 2 is pathologic complete response (pCR). MR volume changes during treatment inform the likelihood that a patient will achieve pCR. Regimens graduate if and when they have a high (Bayesian) predictive probability of success in a subsequent phase 3 neoadjuvant trial within the graduating signature. VC graduated in triple-negative breast cancer with 88% predicted probability of phase 3 success. A total of 72 patients were randomized to VC and 44 to concurrent controls. Respective pCR estimates (95% probability intervals) were 51% (35%–69%) vs 26% (11%–40%). Greater toxicity of VC was manageable. The design of I-SPY 2 has the potential to efficiently identify responding tumor subtypes for the various therapies being evaluated. VC added to standard therapy improves pCR rates specifically in triple-negative breast cancer.