Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT): An MD Anderson Precision Medicine Study.
Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT): An MD Anderson Precision Medicine Study.
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DOI：
10.1200/po.17.00002
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发表时间：
2017
影响因子：
4.6
通讯作者：
Kurzrock R
中科院分区：
文献类型：
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作者：
Tsimberidou AM;Hong DS;Ye Y;Cartwright C;Wheler JJ;Falchook GS;Naing A;Fu S;Piha-Paul S;Janku F;Meric-Bernstam F;Hwu P;Kee B;Kies MS;Broaddus R;Mendelsohn J;Hess KR;Kurzrock R
基因组分析越来越多地用于癌症的管理。我们之前已经报告了我们精准医疗计划的初步结果。在这里，我们介绍了637名额外的患者的反应和生存结果，这些患者被推荐参加I期试验，并在可用时接受匹配的靶向治疗（MTT）。接受肿瘤基因组分析的晚期癌症患者在可用时用MTT治疗。总体而言，1，436例患者中有1，179例（82.1%）有一个或多个改变（中位年龄，59.7岁;男性，41.2%）; 637例有一个或多个可操作的畸变，并接受MTT（n = 390）或非MTT（n = 247）治疗。MTT治疗的患者与未配对的患者相比，完全和部分缓解率更高（11% v5%; P = 0.0099），无失败生存期更长（FFS; 3.4 v2.9个月; P = 0.0015），总生存期更长（OS; 8.4 v7.3个月; P = 0.041）。两个月的里程碑分析显示，对于MTT患者，应答者与无应答者的FFS分别为7.6个月与4.3个月（P < .001），OS为23.4个月vs 8.5个月（P < .001），而对于非MTT患者，（应答者vs无应答者），FFS为6.6 vs 4.1个月（P = .001），OS为15.2 vs 7.5个月（P = .43）。磷脂酰肌醇3-激酶（PI 3 K）和丝裂原活化蛋白激酶通路改变与PI 3 K/Akt/哺乳动物雷帕霉素靶点轴抑制剂单独匹配的患者表现出与不匹配患者相当的结局。我们的研究结果支持使用基因组匹配。亚组分析表明，匹配的患者谁窝藏PI 3 K和丝裂原活化蛋白激酶通路改变，只有PI 3 K通路抑制剂不会改善结果。我们已经启动了IMPACT 2，这是一项随机试验，旨在比较有和没有基因组选择的治疗。
Genomic profiling is increasingly used in the management of cancer. We have previously reported preliminary results of our precision medicine program. Here, we present response and survival outcomes for 637 additional patients who were referred for phase I trials and were treated with matched targeted therapy (MTT) when available. Patients with advanced cancer who underwent tumor genomic analyses were treated with MTT when available. Overall, 1,179 (82.1%) of 1,436 patients had one or more alterations (median age, 59.7 years; men, 41.2%); 637 had one or more actionable aberrations and were treated with MTT (n = 390) or non-MTT (n = 247). Patients who were treated with MTT had higher rates of complete and partial response (11% v 5%; P = .0099), longer failure-free survival (FFS; 3.4 v 2.9 months; P = .0015), and longer overall survival (OS; 8.4 v 7.3 months; P = .041) than did unmatched patients. Two-month landmark analyses showed that, for MTT patients, FFS for responders versus nonresponders was 7.6 versus 4.3 months (P < .001) and OS was 23.4 versus 8.5 months (P < .001), whereas for non-MTT patients (responders v nonresponders), FFS was 6.6 versus 4.1 months (P = .001) and OS was 15.2 versus 7.5 months (P = .43). Patients with phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase pathway alterations matched to PI3K/Akt/mammalian target of rapamycin axis inhibitors alone demonstrated outcomes comparable to unmatched patients. Our results support the use of genomic matching. Subset analyses indicate that matching patients who harbor a PI3K and mitogen-activated protein kinase pathway alteration to only a PI3K pathway inhibitor does not improve outcome. We have initiated IMPACT2, a randomized trial to compare treatment with and without genomic selection.