Yang Zuyao, Hackshaw Allan, Feng Qi, Fu Xiaohong, Zhang Yuelun, Mao Chen, Tang Jinling
Division of Epidemiology, the Jockey Club School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong, China.
The Hong Kong Branch of the Chinese Cochrane Centre, the Chinese University of Hong Kong, Hong Kong, China.
Int J Cancer. 2017 Jun 15;140(12):2805-2819. doi: 10.1002/ijc.30691. Epub 2017 Mar 27.
Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non-small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta-analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression-free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC. However, afatinib was more effective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.
吉非替尼、厄洛替尼和阿法替尼是三种广泛用于治疗晚期非小细胞肺癌（NSCLC）的表皮生长因子受体酪氨酸激酶抑制剂（EGFR TKIs），已证实具有疗效。我们进行了一项系统评价和荟萃分析，以综合现有关于EGFR TKIs在NSCLC中疗效和安全性直接比较的研究。纳入了八项随机试验和82项队列研究，共17621例患者进行分析。吉非替尼和厄洛替尼在无进展生存期（风险比[HR]，1.00；95%置信区间[CI]，0.95至1.04）、总生存期（HR，0.99；95%CI，0.93至1.06）、总缓解率（风险比[RR]，1.05；95%CI，1.00至1.11）和疾病控制率（RR，0.98；95%CI，0.96至1.01）方面显示出相当的效果，且这些效果在EGFR突变状态、种族、治疗线数和基线脑转移状态方面没有显著差异。吉非替尼与更多的3/4级肝功能障碍相关，但导致剂量减少、治疗中断、3/4级不良事件总数（RR，0.78；95%CI 0.65至0.94）以及一些特定不良事件（如皮疹和腹泻）的发生率较低。没有确凿证据表明阿法替尼在EGFR突变NSCLC的一线治疗中比吉非替尼或厄洛替尼具有更高的疗效。然而，在晚期鳞状细胞癌患者的二线治疗中，阿法替尼比厄洛替尼更有效。阿法替尼的3/4级不良事件发生率与厄洛替尼相当，但高于吉非替尼。
