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晚期非小细胞肺癌的抗血管生成治疗:III期随机试验的荟萃分析

Antiangiogenic Therapy in Advanced Non-small-cell Lung Cancer: A Meta-analysis of Phase III Randomized Trials.

作者信息

Raphael Jacques, Chan Kelvin, Karim Safiya, Kerbel Robert, Lam Henry, Santos Keemo Delos, Saluja Ronak, Verma Sunil

机构信息

Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.

Medical Oncology Division, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada.

出版信息

Clin Lung Cancer. 2017 Jul;18(4):345-353.e5. doi: 10.1016/j.cllc.2017.01.004. Epub 2017 Jan 12.

Abstract

We conducted a meta-analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non-small-cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology. and AT dose. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated. We divided the population into 2 subgroups based on the bevacizumab dose. Data of 19,098 patients from 25 phase III trials were analyzed. Compared with the standard of care, the addition of AT did not prolong OS (HR 0.98; 95% confidence interval [CI], 0.96-1.00; P = .1 and HR 0.97; 95% CI, 0.94-1.00; P = .06 for groups 1 and 2, respectively). However, there was a significant improvement in PFS with the addition of AT (HR 0.85; 95% CI, 0.79-0.91; P < .00001 and HR 0.81; 95% CI, 0.75-0.88; P < .00001 for groups 1 and 2, respectively) and overall RR (OR 1.61; 95% CI, 1.30-2.01; P < .0001 and OR 1.72; 95% CI, 1.39-2.14; P < .00001 for groups 1 and 2, respectively). This is the first meta-analysis including only all phase III trials with AT in NSCLC showing no significant effect on OS and an improvement in PFS and RR only. The role of AT in advanced NSCLC is still questionable; strong validated biomarkers are eagerly needed to predict which subgroup might benefit the most from such therapy.

摘要

我们进行了一项荟萃分析,以评估在晚期非小细胞肺癌(NSCLC)的标准治疗中添加任何抗血管生成疗法(AT)的疗效。检索了电子数据库Ovid PubMed、Cochrane对照试验中央注册库和Embase,以确定符合条件的试验。我们纳入了所有III期随机试验,包括任何治疗线数、治疗类型、组织学类型和AT剂量。计算了总生存期(OS)和无进展生存期(PFS)的合并风险比(HR),以及总缓解率(RR)的合并比值比(OR)。我们根据贝伐单抗剂量将人群分为2个亚组。分析了来自25项III期试验的19098例患者的数据。与标准治疗相比,添加AT并未延长OS(第1组和第2组的HR分别为0.98;95%置信区间[CI],0.96 - 1.00;P = 0.1和HR 0.97;95% CI,0.94 - 1.00;P = 0.06)。然而,添加AT后PFS有显著改善(第1组和第2组的HR分别为0.85;95% CI,0.79 - 0.91;P < 0.00001和HR 0.81;95% CI,0.75 - 0.88;P < 0.00001),总RR也有显著改善(第1组和第2组的OR分别为1.61;95% CI,1.30 - 2.01;P < 0.0001和OR 1.72;95% CI,1.39 - 2.14;P < 0.00001)。这是第一项仅纳入所有NSCLC中含AT的III期试验的荟萃分析,结果显示对OS无显著影响,仅PFS和RR有所改善。AT在晚期NSCLC中的作用仍存在疑问;迫切需要强有力的经过验证的生物标志物来预测哪些亚组可能从这种治疗中获益最大。

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