广州医科大学附属第一医院何建行教授、梁文华副教授等对晚期表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）一线治疗的疗效和安全性进行了系统评价和网络荟萃分析。这一研究成果于2019年10月7日在线发表于《英国医学杂志》。

研究组在PubMed、Embase、Cochrane中央对照试验注册中心和ClnicalTrials.gov等知名数据库中检索2019年5月20日之前符合标准的文献。入选研究均比较了晚期EGFR突变NSCLC患者一线治疗中两种以上的疗法，且至少报告以下临床结果指标之一：无进展生存、总生存、客观缓解率和3级及以上不良反应。

18项符合条件的试验包括4628例患者和12种治疗方法：EGFR酪氨酸激酶抑制剂（TKIs），基于培美曲塞的化疗，培美曲塞游离化疗以及联合治疗。与吉非替尼+培美曲塞化疗的疗效相当，奥希替尼显示出最有利的无进展生存期（风险比为0.95），显著优于达克替尼（0.74）、阿法替尼（0.52）、厄洛替尼（0.48）、吉非替尼（0.44）、埃克替尼（0.39）、培美曲塞为基础的化疗（0.24）、培美曲塞游离化疗（0.16）、阿法替尼+西妥昔单抗（0.44）和吉非替尼+培美曲塞（0.65）。

奥希替尼和吉非替尼联合以培美曲塞为基础的化疗在提供最佳总体生存效益方面也大致相当（风险比为0.94）。但联合治疗引起的毒性更大，尤其是厄洛替尼+贝伐单抗，易导致3级以上的严重不良事件。不同的EGFR-TKIs显示出不同毒性谱。两种最常见的EGFR突变类型的亚组分析表明，在外显子19缺失的患者中，奥希替尼与最佳无进展生存相关，而在Leu858Arg突变患者中，吉非替尼+培美曲塞化疗与最佳无进展生存相关。

总之，与其他一线治疗相比，奥希替尼和吉非替尼+培美曲塞化疗可显著提高晚期EGFR突变的NSCLC患者的无进展生存期和总生存期。对于外显子19缺失和Leu858Arg突变的患者，奥希替尼和吉非替尼+培美曲塞化疗的无进展生存最优。

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何建行 教授，博士，博士研究生导师。广州医科大学附属第一医院胸外科主任。专业方向： 胸外科肺部肿瘤的早期诊断与治疗、晚期慢性阻塞性肺部疾病的治疗。（据广州医科大学附属第一医院）

梁文华 副教授，博士研究生导师。广州医科大学附属第一医院肿瘤科主任助理。专业方向： 肺癌及肺部结节的综合诊治，尤其基因检测、靶向治疗及免疫治疗、术后跟踪等。（据广州医科大学附属第一医院）

附：英文原文

Title: Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis

Author: Yi Zhao, Jingting Liu, Xiuyu Cai, Zhenkui Pan, Jun Liu, Weiqiang Yin, Hanzhang Chen, Zhanhong Xie, Hengrui Liang, Wei Wang, Zhihua Guo, Shen Zhao, Wenhua Liang, Jianxing He

Issue&Volume: 2019/10/07

Abstract: 

Objective To compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC).

Design Systematic review and network meta-analysis.

Data sources PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and several international conference databases, from inception to 20 May 2019.

Eligibility criteria for selecting studies Published and unpublished randomised controlled trials comparing two or more treatments in the first line setting for patients with advanced EGFR mutated NSCLC were included in a bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: progression free survival, overall survival, objective response rate, and adverse events of grade 3 or higher.

Results 18 eligible trials involved 4628 patients and 12 treatments: EGFR tyrosine kinase inhibitors (TKIs; osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed based chemotherapy, pemetrexed free chemotherapy, and combination treatments (afatinib plus cetuximab, erlotinib plus bevacizumab, gefitinib plus pemetrexed based chemotherapy, and gefitinib plus pemetrexed). Consistent with gefitinib plus pemetrexed based chemotherapy (hazard ratio 0.95, 95% credible interval 0.72 to 1.24), osimertinib showed the most favourable progression free survival, with significant differences versus dacomitinib (0.74, 0.55 to 1.00), afatinib (0.52, 0.40 to 0.68), erlotinib (0.48, 0.40 to 0.57), gefitinib (0.44, 0.37 to 0.52), icotinib (0.39, 0.24 to 0.62), pemetrexed based chemotherapy (0.24, 0.17 to 0.33), pemetrexed free chemotherapy (0.16, 0.13 to 0.20), afatinib plus cetuximab (0.44, 0.28 to 0.71), and gefitinib plus pemetrexed (0.65, 0.46 to 0.92). Osimertinib and gefitinib plus pemetrexed based chemotherapy were also consistent (0.94, 0.66 to 1.35) in providing the best overall survival benefit. Combination treatments caused more toxicity in general, especially erlotinib plus bevacizumab, which caused the most adverse events of grade 3 or higher. Different toxicity spectrums were revealed for individual EGFR-TKIs. Subgroup analyses by the two most common EGFR mutation types indicated that osimertinib was associated with the best progression free survival in patients with the exon 19 deletion, and gefitinib plus pemetrexed based chemotherapy was associated with the best progression free survival in patients with the Leu858Arg mutation.

Conclusions These results indicate that osimertinib and gefitinib plus pemetrexed based chemotherapy were associated with the best progression free survival and overall survival benefits for patients with advanced EGFR mutated NSCLC, compared with other first line treatments. The treatments resulting in the best progression free survival for patients with the exon 19 deletion and Leu858Arg mutations were osimertinib and gefitinib plus pemetrexed based chemotherapy, respectively.

DOI: 10.1136/bmj.l5460

Source: https://www.bmj.com/content/367/bmj.l5460