Personalized medicine for patients with advanced cancer in the phase I program at MD Anderson: validation and landmark analyses.
Personalized medicine for patients with advanced cancer in the phase I program at MD Anderson: validation and landmark analyses.
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DOI：
10.1158/1078-0432.ccr-14-0603
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发表时间：
2014-09-15
期刊：
影响因子：
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通讯作者：
Berry D
中科院分区：
文献类型：
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作者：
Tsimberidou AM;Wen S;Hong DS;Wheler JJ;Falchook GS;Fu S;Piha-Paul S;Naing A;Janku F;Aldape K;Ye Y;Kurzrock R;Berry D
这项研究的目的是证实我们之前的结果，即与肿瘤分子改变匹配的靶向药物与晚期癌症患者的治疗相比，与不匹配的治疗结果相关。将2011年3月至2012年1月在德克萨斯大学MD安德森癌症中心进行的I期临床试验中转诊接受治疗的患者的结果在接受靶向治疗的患者和未接受靶向治疗的患者之间进行比较。结合先前发表的和验证队列患者数据，进行了为期两个月的总体和无进展生存(PFS)的里程碑式分析。在有1个改变的患者中，匹配治疗与非匹配治疗相比，客观有效率(12%vs.5%；P<；0.0001)、PFS(中位数3.9月vs.2.2个月；P=0.001)和生存期(中位数11.4个月vs.8.6个月；P=0.001)显著增加。在多因素分析中，匹配治疗是预测疗效(P<；0.015)和PFS(P<；0.004)的独立因素。配对治疗组的两个月里程碑分析显示，有效组的中位生存期为30.5月，无反应组为11.3个月(P=0.0001)；中位PFS为38.7月，无效组为5.9月(P<；0.0001)。非匹配治疗组分别为9.8个月和9.4个月(P=0.46)和8.5个月和4.2个月(P=0.18)。这一验证分析证实了我们之前的观察结果。在匹配治疗组中，2个月的里程碑式分析表明，有反应的人比无反应的人有更长的生存期和PFS。
The purpose of this study was to confirm our previous results that targeted agents matched with tumor molecular alterations were associated with improved outcomes compared to non-matched therapy in patients with advanced cancer. Outcomes of patients who were referred for treatment on phase I clinical trials at The University of Texas MD Anderson Cancer Center from 3/2011 to 1/2012 were compared between those who had received targeted therapy and those for whom no targeted therapy was available. Two-month landmark analyses for overall and progression-free survival (PFS) combining previously published and validation cohort patient data were performed. In patients with 1 alteration, matched therapy (n=143) compared with treatment without matching (n=236) was associated with a higher objective response rate (12% vs. 5%; P<0.0001), longer PFS (median, 3.9 vs. 2.2 months; P=0.001), and longer survival (median, 11.4 vs. 8.6 months; P=0.04). In multivariate analysis, matched therapy was an independent factor predicting response (P<0.015) and PFS (P<0.004). Two-month landmark analyses in the matched therapy group demonstrated that the median survival of responders was 30.5 months compared to 11.3 months for non-responders (P=0.01); and the median PFS was 38.7 months compared to 5.9 months, respectively (P<0.0001). The respective values in the non-matched therapy group were 9.8 and 9.4 months (P=0.46) and 8.5 and 4.2 months (P=0.18). This validation analysis confirms our previous observations. In the matched therapy group, 2-month landmark analyses demonstrated that responders have longer survival and PFS than non-responders.