Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea3Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
JAMA. 2014 Apr 9;311(14):1430-7. doi: 10.1001/jama.2014.3314.
Current guidelines recommend both epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic chemotherapy drugs as standard treatment options for patients with wild-type (WT) EGFR who were previously treated for non-small cell lung cancer (NSCLC). However, it is not clear that EGFR TKIs are as efficacious as chemotherapy in patients with WT EGFR.
To determine the association between first-generation EGFR TKI vs chemotherapy and survival in advanced NSCLC patients with WT EGFR.
PubMed, EMBASE, Cochrane database, and meeting abstracts of the American Society of Clinical Oncology and European Society of Medical Oncology through December 2013.
Eligible studies were randomized controlled trials comparing EGFR TKI with conventional chemotherapy in patients with advanced NSCLC. Out of 1947 retrieved articles, 11 trials incorporating 1605 patients with WT EGFR were included.
Two reviewers extracted trial characteristics and outcomes. The risk of bias was evaluated using the Cochrane tool. All measures were pooled using random-effects models and 95% CIs were calculated.
The primary outcome was progression-free survival (PFS), measured as hazard ratios (HRs). The secondary outcomes were objective response rate and overall survival, expressed as relative risks and HRs, respectively.
Among patients with WT EGFR tumors, chemotherapy was associated with improvement of PFS, compared with TKI (HR for TKI, 1.41; 95% CI, 1.10-1.81). No statistically significant subgroup difference was identified in terms of line of treatment (first-line vs second- or later-line), experimental drug, dominant ethnicity, or EGFR mutation analysis method. Trials using more sensitive platforms than direct sequencing were associated with a significant PFS benefit with chemotherapy (HR for TKI, 1.84; 95% CI, 1.35-2.52). The association of chemotherapy with improvement in PFS was also significant in second- or later-line trials (HR, 1.34; 95% CI, 1.09-1.65). The objective response rate was higher with chemotherapy (92/549, 16.8%, vs 39/540, 7.2%, for TKI; relative risk for TKI, 1.11; 95% CI, 1.02-1.21); however, no statistically significant difference was observed with respect to overall survival (HR for TKI, 1.08; 95% CI, 0.96-1.22).
Among patients with advanced NSCLC harboring WT EGFR, conventional chemotherapy, compared with first-generation EGFR TKI, was associated with improvement in PFS but not overall survival.
目前的指南建议表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）和细胞毒性化疗药物作为先前治疗过非小细胞肺癌（NSCLC）的野生型（WT）EGFR 患者的标准治疗选择。然而，目前尚不清楚 EGFR TKI 在 WT EGFR 患者中的疗效是否与化疗相当。
确定第一代 EGFR TKI 与化疗在 WT EGFR 晚期 NSCLC 患者中的生存相关性。
通过 PubMed、EMBASE、Cochrane 数据库以及美国临床肿瘤学会和欧洲肿瘤内科学会的会议摘要，检索截至 2013 年 12 月的文献。
纳入比较 EGFR TKI 与常规化疗治疗晚期 NSCLC 患者的随机对照试验。在检索到的 1947 篇文章中，有 11 项试验纳入了 1605 例 WT EGFR 患者。
两位评审员提取试验特征和结局。使用 Cochrane 工具评估偏倚风险。使用随机效应模型汇总所有指标，并计算 95%置信区间。
主要结局是无进展生存期（PFS），以风险比（HR）表示。次要结局是客观缓解率和总生存期，分别用相对风险和 HR 表示。
在 WT EGFR 肿瘤患者中，与 TKI 相比，化疗可改善 PFS（TKI 的 HR，1.41；95%CI，1.10-1.81）。在治疗线数（一线 vs 二线或以后线）、实验药物、主要种族或 EGFR 突变分析方法方面，未发现有统计学意义的亚组差异。与直接测序相比，使用更敏感平台的试验与化疗的 PFS 获益显著相关（TKI 的 HR，1.84；95%CI，1.35-2.52）。在二线或以后线的试验中，化疗也与 PFS 改善显著相关（HR，1.34；95%CI，1.09-1.65）。与 TKI 相比，化疗的客观缓解率更高（92/549，16.8% vs 39/540，7.2%；TKI 的相对风险，1.11；95%CI，1.02-1.21），但总生存期无统计学差异（TKI 的 HR，1.08；95%CI，0.96-1.22）。
在携带 WT EGFR 的晚期 NSCLC 患者中，与第一代 EGFR TKI 相比，常规化疗与 PFS 改善相关，但与总生存期无关。
