Li Xuyuan, Wang Hongbiao, Lin Wenzhao, Xu Qini
Department of Internal Medicine, Cancer Hospital of Shantou University Medical College , Shantou, Guangdong , China.
Curr Med Res Opin. 2014 Nov;30(11):2295-304. doi: 10.1185/03007995.2014.909392. Epub 2014 Apr 30.
To compare the effects of adding targeted agents to standard second-line chemotherapy with a single agent (pemetrexed or docetaxel) in patients with advanced NSCLC, a meta-analysis of all relevant randomized controlled trials was performed and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were assessed.
The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and December 2013. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.
Fourteen trials with a total of 6922 patients were included in this meta-analysis. Compared with chemotherapy, combination therapy did not improve OS (HR = 0.95; 95% CI, 0.90-1.01; P = 0.081) but improved PFS (HR = 0.83; 95% CI, 0.78-0.87; P = 0.000). Survival outcomes did not differ significantly among trials. Combination therapy significantly increased ORR (RR = 1.83; 95% CI, 1.59-2.127; P = 0.000) and DCR (RR = 1.18; 95% CI, 1.13-1.23, P = 0.000). Sub-analysis indicated that adding targeted therapy to chemotherapy significantly prolonged OS in patients with non-squamous NSCLC (HR = 0.87; 95% CI, 0.87-0.97; P = 0.009). Patients treated with combination therapy had an increased incidence of grade 3 or greater diarrhea (RR = 1.96; 95% CI, 1.37-2.81; P = 0.000), neutropenia (RR = 1.27, 95% CI, 1.14-1.61; P = 0.000) and thrombocytopenia (RR = 4.21, 95% CI, 1.87-9.51; P = 0.001). This meta-analysis has the limitations of heterogeneity among the included trials and not using individual patient data.
In the second-line treatment of advanced NSCLC, the combination of targeted therapy and chemotherapy significantly increased response rates and progression-free survival, but did not improve overall survival and was more toxic.
为比较在晚期非小细胞肺癌（NSCLC）患者中，在标准二线化疗基础上加用靶向药物与单药（培美曲塞或多西他赛）治疗的效果，我们进行了一项对所有相关随机对照试验的荟萃分析，并评估了总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和疾病控制率（DCR）。
检索PubMed和Embase数据库以及Cochrane对照试验中心注册库，查找2000年1月至2013年12月期间报告随机对照试验的相关出版物。得出风险比（HRs）及其95%置信区间（CIs），或用于计算95% CIs的HRs的数据。
本荟萃分析纳入了14项试验，共6922例患者。与化疗相比，联合治疗未改善OS（HR = 0.95；95% CI，0.90 - 1.01；P = 0.081），但改善了PFS（HR = 0.83；95% CI，0.78 - 0.87；P = 0.000）。各试验间生存结果无显著差异。联合治疗显著提高了ORR（RR = 1.83；95% CI，1.59 - 2.127；P = 0.000）和DCR（RR = 1.18；95% CI，1.13 - 1.23，P = 0.000）。亚组分析表明，在化疗基础上加用靶向治疗可显著延长非鳞状NSCLC患者的OS（HR = 0.87；95% CI，0.87 - 0.97；P = 0.009）。接受联合治疗的患者3级或更高级别腹泻（RR = 1.96；95% CI，1.37 - 2.81；P = 0.000）、中性粒细胞减少（RR = 1.27，95% CI，1.14 - 1.61；P = 0.000）和血小板减少（RR = 4.21，95% CI，1.87 - 9.51；P = 0.001）的发生率增加。本荟萃分析存在纳入试验间异质性以及未使用个体患者数据的局限性。
在晚期NSCLC的二线治疗中，靶向治疗与化疗联合可显著提高缓解率和无进展生存期，但未改善总生存期且毒性更大。
