Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: Meta-analysis of phase III trials
Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: Meta-analysis of phase III trials
复制标题
DOI：
10.1016/j.lungcan.2011.04.008
复制
发表时间：
2011-12-01
期刊：
影响因子：
5.3
通讯作者：
Lopes, Gilberto de Lima, Jr.
中科院分区：
文献类型：
--
作者：
Ku, Geoffrey Y.;Haaland, Benjamin A.;Lopes, Gilberto de Lima, Jr.
背景：吉非替尼是一种口服酪氨酸激酶抑制剂，可抑制表皮生长因子受体（EGFR）。它已被证明是积极的晚期非小细胞肺癌（NSCLC）患者的肿瘤含有EGFR mutations.Methods：我们进行了荟萃分析的四个随机研究，比较吉非替尼与化疗一线治疗晚期NSCLC患者：IPASS，东北日本，西日本和第一信号研究。选择患者的基础上已知的EGFR突变或根据临床病理标准-非吸烟者腺癌-与EGFR突变的可能性增加。结果：近2000例患者参加了这四项试验。中位年龄范围为57至64岁。其中76%为女性，86%为非吸烟者。总体而言，吉非替尼与化疗相比毒性显著降低，生活质量改善。吉非替尼在EGFR突变阳性患者中也产生了更高的缓解率（72% vs. 38%，比值比4.04，p < 10（-15）），以及改善的无进展生存期（PFS;风险比0.45，p < 10（-16））。总生存期（OS）治疗组之间没有显着差异（p = 0.35）。结论：这项荟萃分析证实了每个单独的研究结果，并缩小了这些结果的置信区间。在已知EGFR突变或肿瘤可能携带突变的患者中，前期吉非替尼或化疗与相似的OS相关。吉非替尼与化疗相比，疲劳、骨髓抑制和恶心较少（但产生更多皮疹、腹泻和肺炎）。与接受化疗的患者相比，接受吉非替尼的患者生活质量有所改善，使其成为合适的一线选择。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Background: Gefitinib is an oral tyrosine kinase inhibitor against the epidermal growth factor receptor (EGFR). It has been shown to be active in patients with advanced non-small cell lung cancer (NSCLC) whose tumors contain EGFR mutations.Methods: We performed a meta-analysis of four randomized studies that compared gefitinib with chemotherapy in the first-line treatment of patients with advanced NSCLC: IPASS, North-East Japan, West Japan and first-SIGNAL studies. Patients were selected either on the basis of known EGFR mutations or based on clinicopathologic criteria - non-smokers with adenocarcinomas - associated with increased likelihood of EGFR mutations.Results: Nearly 2000 patients were enrolled on these four trials. Median ages ranged from 57 to 64 years. Seventy-six percent were women and 86% were non-smokers. Overall, gefitinib was associated with significantly less toxicity than chemotherapy and improved quality-of-life. Gefitinib also produced higher response rates in the EGFR mutation-positive patients (72% vs. 38%, odds ratio 4.04, p < 10(-15)), as well as improved progression-free survival (PFS; hazard ratio 0.45, p < 10(-16)). Overall survival (OS) was not significantly different between treatment groups (p = 0.35).Conclusions: This meta-analysis confirms the results of each individual study and narrows the confidence intervals of these results. In patients with known EGFR mutations or whose tumors are likely to harbor a mutation, upfront gefitinib or chemotherapy are associated with similar OS. Gefitinib is associated with less fatigue, myelosuppression and nausea than chemotherapy (but produces more skin rash, diarrhea and pneumonitis). Patients receiving gefitinib have improved quality-of-life compared to those receiving chemotherapy, making it an appropriate first-line choice. (C) 2011 Elsevier Ireland Ltd. All rights reserved.