Liu Yuanyuan, Zhang Yu, Feng Gangling, Niu Qiang, Xu Shangzhi, Yan Yizhong, Li Shugang, Jing Mingxia
Department of Public Health, School of Medicine, Shihezi University, Shihezi, Xinjiang 832002, P.R. China.
Key Laboratory of Xinjiang Endemic and Ethnic Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang 832002, P.R. China.
Exp Ther Med. 2017 Nov;14(5):4017-4032. doi: 10.3892/etm.2017.5094. Epub 2017 Sep 1.
The present network meta-analysis aimed to compare the effectiveness and adverse effects of gefitinib, erlotinib and icotinib in the treatment of patients with non-small cell lung cancer (NSCLC). Two reviewers searched the Cochrane, PubMed, Embase, ScienceDirect, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals and Wanfang databases for relevant studies. Studies were then screened and evaluated, and data was extracted. End-points evaluated for NSCLC included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), median survival time (MST) and adverse effects, including rash, diarrhea, nausea and vomiting, fatigue and abnormal liver function. For the analysis of incorporated studies, RevMan, SPSS, R and Stata software were used. A total of 43 studies with 7,168 patients were included in the network meta-analysis. No significant differences were observed in CR, PR, SD, PD, ORR or DCR between gefitinib, erlotinib and icotinib by using network meta analysis. Compared with gefitinib, erlotinib resulted in a higher rate of nausea and vomiting [adjusted odds ratio (OR)=2.0; 95% credible interval, 1.1-3.7]. However, no significant differences were observed in the rates of rash, diarrhea, fatigue or abnormal liver function using network meta-analysis. Compared with erlotinib, gefitinib resulted in a lower SD rate [OR=0.86; 95% confidence interval (CI): 0.75-0.99; P=0.04], and lower rates of rash (OR=0.45; 95% CI, 0.36-0.55; P<0.00001), diarrhea (OR=0.75; 95% CI, 0.61-0.92; P=0.005), nausea and vomiting (OR=0.47; 95% CI, 0.27-0.84; P=0.01) and fatigue (OR=0.43; 95% CI, 0.24-0.76; P=0.004) through meta-analysis of two congruent drugs. However, gefitinib resulted in a higher rate of rash compared with icotinib (OR=1.57; 95% CI, 1.18-2.09; P=0.002). Otherwise, no significant differences were observed in CR, PR, PD, ORR, DCR and abnormal liver function between gefitinib, erlotinib and icotinib through meta-analysis of two congruent drugs. The PFS rate for gefitinib, erlotinib and icotinib was 5.48, 5.15 and 5.81 months, respectively. The MST was 13.26, 13.52, 12.58 months for gefitinib, erlotinib and icotinib, respectively. Gefitinib and icotinib resulted in significantly higher PFS rates compared with erlotinib (P<0.05). Erlotinib resulted in a significantly longer MST compared with gefitinib and icotinib (P<0.05). In conclusion, gefitinib, erlotinib and icotinib had similar effectiveness for the treatment of patients with advanced NSCLC. However, gefitinib resulted in a lower frequency of fatigue, and nausea and vomiting, compared with the other two drugs. Icotinib resulted in a lower frequency of rash. Erlotinib resulted in a longer MST, but was also associated with a higher frequency of rash, and nausea and vomiting.
本网状Meta分析旨在比较吉非替尼、厄洛替尼和埃克替尼治疗非小细胞肺癌（NSCLC）患者的有效性和不良反应。两名研究者检索了Cochrane、PubMed、Embase、ScienceDirect、中国知网、维普中文科技期刊数据库和万方数据库中的相关研究。随后对研究进行筛选和评估，并提取数据。评估NSCLC的终点指标包括完全缓解（CR）、部分缓解（PR）、疾病稳定（SD）、疾病进展（PD）、总缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、中位生存时间（MST）以及不良反应，包括皮疹、腹泻、恶心、呕吐、疲劳和肝功能异常。对于纳入研究的分析，使用了RevMan、SPSS、R和Stata软件。网状Meta分析共纳入43项研究，涉及7168例患者。通过网状Meta分析，未观察到吉非替尼、厄洛替尼和埃克替尼在CR、PR、SD、PD、ORR或DCR方面存在显著差异。与吉非替尼相比，厄洛替尼导致恶心和呕吐的发生率更高[调整优势比（OR）=2.0；95%可信区间，1.1 - 3.7]。然而，通过网状Meta分析，在皮疹、腹泻、疲劳或肝功能异常的发生率方面未观察到显著差异。与厄洛替尼相比，吉非替尼导致疾病稳定率较低[OR = 0.86；95%置信区间（CI）：0.75 - 0.99；P = 0.04]，皮疹（OR = 0.45；95% CI，0.36 - 0.55；P < 0.00001）、腹泻（OR = 0.75；95% CI，0.61 - 0.92；P = 0.005）、恶心和呕吐（OR = 0.47；95% CI，0.27 - 0.84；P = 0.01）以及疲劳（OR = 0.43；95% CI，0.24 - 0.76；P = .004）的发生率较低。然而，与埃克替尼相比，吉非替尼导致皮疹发生率较高（OR = 1.57；95% CI，1.18 - 2.09；P = 0.002）。此外，通过对两种同类药物的Meta分析，未观察到吉非替尼、厄洛替尼和埃克替尼在CR、PR、PD、ORR、DCR和肝功能异常方面存在显著差异。吉非替尼、厄洛替尼和埃克替尼的PFS率分别为5.48、5.15和5.81个月。吉非替尼、厄洛替尼和埃克替尼的MST分别为13.26、13.52和12.58个月。与厄洛替尼相比，吉非替尼和埃克替尼导致PFS率显著更高（P < 0.05）。与吉非替尼和埃克替尼相比，厄洛替尼导致MST显著更长（P < 0.05）。总之，吉非替尼、厄洛替尼和埃克替尼在治疗晚期NSCLC患者方面具有相似的有效性。然而，与其他两种药物相比，吉非替尼导致疲劳、恶心和呕吐的频率较低。埃克替尼导致皮疹的频率较低。厄洛替尼导致MST更长，但也与皮疹、恶心和呕吐的频率较高相关。
