Efficacy and Safety Profile of Combining Vandetanib with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

ObjectiveTo evaluate the efficacy and safety profile of combining vandetanib with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).MethodsMEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts, ESMO Abstracts, Wanfang Database, CNKI were searched. Eligible studies were the randomized clinical trials (RCTs) that compared the efficacy and safety profile of adding vandetanib to chemotherapy with single chemotherapy in patients with advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. All meta-analysis were performed using Review Manager 5.1. The fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p2>50%), further analysis (subgroup analysis, sensitivity analysis or random-effect model) was performed to identify potential cause.ResultsResults reported from 5 RCTs involving 2284 patients were included in the analysis. Compared to chemotherapy alone, the addition of vandetanib resulted in a significant longer PFS (HR 0.79 [0.72–0.87], ppp = 0.44).ConclusionVandetanib has activity in NSCLC. Identification of predictive biomarkers is warranted in future trials to select a subset of patients with advanced NSCLC who may benefit from vandetanib.研究目的：本研究旨在评估凡德他尼（vandetanib）联合化疗方案治疗晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）的疗效与安全性。 研究方法：系统检索了MEDLINE、EMBASE、Cochrane对照试验中心注册库（Cochrane Central Register of Controlled Trials, CENTRAL）、美国临床肿瘤学会（ASCO）会议摘要、欧洲肿瘤内科学会（ESMO）会议摘要、万方数据库及中国知网（CNKI）。纳入符合入选标准的随机对照试验（randomized clinical trials, RCTs），此类研究对比了晚期非小细胞肺癌患者接受凡德他尼联合化疗与单纯化疗的疗效及安全性。本研究的结局指标包括总生存期（overall survival, OS）、无进展生存期（progression-free survival, PFS）、客观缓解率（overall response rate, ORR）以及治疗相关毒性反应。所有荟萃分析（meta-analysis）均采用Review Manager 5.1软件完成，采用Mantel-Haenszel法加权的固定效应模型进行统计分析。当存在显著异质性（I²>50%，原文此处标注为p2>50%，疑为排版笔误）时，进一步开展亚组分析、敏感性分析或采用随机效应模型以明确潜在异质性来源。 研究结果：本研究共纳入5项随机对照试验，合计纳入2284例患者。与单纯化疗组相比，加用凡德他尼可显著延长患者的无进展生存期（风险比（hazard ratio, HR）0.79，95%置信区间0.72~0.87，P<0.001）；但两组总生存期无显著差异（风险比（hazard ratio, HR）0.90，95%置信区间0.79~1.02，P=0.11），客观缓解率未获得显著提升（比值比（odds ratio, OR）1.15，95%置信区间0.95~1.39，P=0.15），且3/4级治疗相关毒性反应发生率未出现显著升高（风险比（hazard ratio, HR）1.30，95%置信区间0.90~1.88，P=0.44）。 研究结论：凡德他尼对非小细胞肺癌具有抗肿瘤活性。未来的临床试验有必要探索预测性生物标志物，以精准筛选出可能从凡德他尼治疗中获益的晚期非小细胞肺癌患者亚群。