Sheng Zhixin, Zhang Yanxia
*Department of Hematology, Weifang People's Hospital, Weifang †Department of Oncology, Lin Yi People's Hospital, Linyi, Shandong, China.
Am J Clin Oncol. 2017 Aug;40(4):362-369. doi: 10.1097/COC.0000000000000179.
To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC) patients with wild-type (WT) EGFR tumors, we performed an indirect meta-analysis to assess the treatment effects of EGFR-TKIs in such patients.
We searched for randomized controlled trials in Medline, Embase, the Cochrane controlled trials register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Effect measures used were hazard ratios (HR) for progression-free survival (PFS) and overall survival.
Out of 2134 retrieved articles, 25 randomized controlled trials including more than 4467 patients were identified. This pooled analysis showed the inferior efficacy of TKI over chemotherapy among patients with WT EGFR NSCLC in terms of PFS (HR, 1.37; 95% confidence interval [CI]: 1.10, 1.72; P=0.006). When used as first-line treatment, TKIs have also fared worse than chemotherapy when compared with standard platinum doublet regimens in patients with WT EGFR in terms of PFS (HR, 2.15; 95% CI: 1.68, 2.76; P<0.001). And, the same inferior trend was found with TKIs in those trials of second-line/third-line treatment in terms of PFS (HR, 1.35; 95% CI: 1.13, 1.61; P<0.001). However, according to the pooled results, EGFR-TKIs still produced a reduction of 19% in the risk of progression over placebo in such WT EGFR patients ineligible for further chemotherapy (HR, 0.81; 95% CI: 0.68, 0.97; P=0.02). Furthermore, addition of EGFR-TKI to chemotherapy resulted in an improvement of PFS over chemotherapy alone (HR, 0.83; 95% CI: 0.71, 0.96; P=0.01).
Among patients with advanced NSCLC harboring WT EGFR, EGFR-TKIs were inferior to standard chemotherapy both for first-line treatment and for second-line/third-line treatment, but still superior to placebo in patients unfit for further chemotherapy. And, addition of EGFR-TKIs to chemotherapy could provide additive benefit over chemotherapy alone in such patients.
为了确定第一代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）在野生型（WT）EGFR肿瘤的晚期非小细胞肺癌（NSCLC）患者中的疗效，我们进行了一项间接荟萃分析，以评估EGFR-TKIs在此类患者中的治疗效果。
我们在Medline、Embase、Cochrane对照试验注册库、科学引文索引和美国临床肿瘤学会年会上检索随机对照试验。使用的效应指标为无进展生存期（PFS）和总生存期的风险比（HR）。
在检索到的2134篇文章中，确定了25项随机对照试验，纳入患者超过4467例。这项汇总分析显示，在PFS方面，WT EGFR NSCLC患者中TKI的疗效低于化疗（HR，1.37；95%置信区间[CI]：1.10，1.72；P = 0.006）。在WT EGFR患者中，与标准铂类双联方案相比，当作为一线治疗时，TKI在PFS方面也比化疗差（HR，2.15；95% CI：1.68，2.76；P < 0.001）。而且，在二线/三线治疗的试验中，TKI在PFS方面也有同样的劣势（HR，1.35；95% CI：1.13，1.61；P < 0.001）。然而，根据汇总结果，在不适合进一步化疗的此类WT EGFR患者中，EGFR-TKIs与安慰剂相比，疾病进展风险仍降低了19%（HR，0.81；95% CI：0.68，0.97；P = 0.02）。此外，在化疗中添加EGFR-TKI比单纯化疗改善了PFS（HR，0.83；95% CI：0.71，0.96；P = 0.01）。
在携带WT EGFR的晚期NSCLC患者中，EGFR-TKIs在一线治疗和二线/三线治疗中均劣于标准化疗，但在不适合进一步化疗的患者中仍优于安慰剂。而且，在化疗中添加EGFR-TKIs对此类患者可能比单纯化疗有额外益处。
