Background and objective: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been used for the first-line treatment of non-small cell lung cancer (NSCLC) and has shown good clinical effects. However, some patients fail to benefit from this treatment. The aim of this study is to analyze whether or not clinical-selected patients (Asian, adenocarcinoma histology, non-smoking) and EGFR mutation-selected patients benefit from EGFR-TKIs or chemotherapy. Our results could be used as basis to guide clinical therapy.
Methods: Randomized controlled trials evaluating the efficacy of EGFR-TKIs versus chemotherapy as first-line treatments of NSCLC were obtained from electronic databases, namely, PubMed, Embase, American Society of Clinical Oncology (ASCO), European Society for Medical Oncology, and China Biology Medicine disc. Assessment, data collection, and statistical analysis were performed according to Cochrane Handbook 5.1.0.
Results: A total of 14 randomized controlled trials with 5,000 patients were included in this study. Compared with the chemotherapy group, EGFR-TKI therapy group in EGFR mutation-selected NSCLC patients showed a higher response rate (RR=2.31; 95%CI: 1.88-2.84) and more significant improvement in progression free survival (PFS; HR=0.39; 95%CI: 0.30-0.49); by contrast, no significant difference was observed in overall survival (OS; HR=0.99; 95%CI: 0.84-1.16). The response rate of clinical-selected patients treated with EGFR-TKI significantly increased (RR=1.30; 95%CI: 1.15-1.47) compared with that of the patients treated with chemotherapy; PFS (HR=0.93; 95%CI: 0.58-1.49) and OS (HR=0.91; 95%CI: 0.81-1.02) of the two groups did not significantly differ. Likewise, the PFS and the OS of the unselected patients in the EGFR-TKI treatment group and the chemotherapy group did not significantly differ, although the OS of the former was shorter than that of the latter.
Conclusions: EGFR mutation-selected patients received more benefits from EGFR-TKI first-line treatment than other treatments. First-line EGFR-TKI treatment was recommended for clinically selected patients who were unsuitable for themotherapy. By comparison, first-line EGFR-TKI treatment was not a suitable choice for unselected patients.
背景与目的 表皮因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor, EGFR-TKI）应用于非小细胞肺癌（non-small cell lung cancer, NSCLC）一线治疗取得较好的临床疗效，然而EGFR-TKI一线用药选择仍面临很多问题。本研究应用循证医学的方法对NSCLC患者临床特征及基因突变情况对一线EGFR-TKIs治疗及化疗获益进行分析，以便指导临床用药。方法 用计算机检索Pubmed、Embase、American Society of Clinical Oncology（ASCO）、European Society for Medical Oncology（ESCO）及生物医学数据库等数据库，寻找出EGFR-TKI与化疗相比一线治疗NSCLC的疗效的随机对照研究（randomized controlled trials, RCT）。对纳入RCT进行资料提取和质量评价，采用Review Manager 5.2软件分析、对比NSCLC患者在TKI治疗中的疗效。结果 纳入的14项研究，共5,000例患者。Meta分析结果显示，EGFR基因突变的NSCLC患者，EGFR-TKIs治疗与化疗相比有较好的近期有效率（RR=2.31; 95%CI: 1.88-2.84）和延长无疾病进展时间（progression free survival, PFS）（HR=0.39; 95%CI: 0.30-0.49），总生存时间（overall survival, OS）上两者无明显差异（HR=0.99; 95%CI: 0.84-1.16）。临床选择（亚裔、腺癌、不吸烟）NSCLC患者，EGFR-TKIs一线治疗与化疗相比也有较好的近期有效率（RR=1.30; 95%CI: 1.15-1.47），PFS和OS无差异（HR=0.93; 95%CI: 0.58-1.49）（HR=0.91; 95%CI: 0.81-1.02）。未经选择的患者，一线EGFR-TKIs治疗有效率、PFS与化疗无差异，但OS劣于一线接受化疗患者。结论 EGFR突变的NSCLC患者一线EGFR-TKIs获益更多；对于不能耐受化疗的亚裔、腺癌、不吸烟患者，推荐一线EGFR-TKIs治疗；未经选择的NSCLC患者一线EGFR-TKIs治疗临床无获益，而且一线EGFR-TKI治疗的OS明显低于一线化疗。.