吉非替尼/吉非替尼联合化疗治疗具有EGFR突变的NSCLC(JCO IF:)NSCLC(JCO IF:)

        1、PURPOSE 目的。Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non–small-cell lung cancer (NSCLC) with EGFR mutations; however, little is known about the efficacy and safety of this combination compared with that of standard therapy with EGFR- tyrosine kinase inhibitors alone.表皮生长因子受体（EGFR）酪氨酸激酶抑制剂与细胞毒性化学疗法联合使用对于治疗具有EGFR突变的晚期非小细胞肺癌（NSCLC）非常有效；然而，与仅使用EGFR-酪氨酸激酶抑制剂的标准疗法相比，该组合的疗效和安全性知之甚少。

　　2、METHODS 方法。We randomly assigned 345 patients with newly diagnosed metastatic NSCLC with EGFR mutations to gefitinib combined with carboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially analyzed as primary end points according to a hierarchical sequential testing method. Secondary end points were objective response rate (ORR), safety, and quality of life.我们将345名新诊断为EGFR突变的转移性NSCLC患者随机分配给吉非替尼联合卡铂加培美曲塞组或吉非替尼单药治疗组。根据分级顺序测试方法，将无进展生存期（PFS），PFS2和总体生存期（OS）作为主要终点进行了顺序分析。次要终点是客观反应率（ORR），安全性和生活质量。
　　
　　3、RESULTS 结果。The combination group demonstrated a better ORR and PFS than the gefitinib group (ORR, 84% v 67% [P , .001]; PFS, 20.9 v 11.9 months; hazard ratio for death or disease progression, 0.490 [P , .001]), although PFS2 was not significantly different (20.9 v 18.0 months; P = .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9 v 38.8 months; hazard ratio for death, 0.722; P = .021). The rate of grade $ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3% v 31.0%); there were no differences in quality of life. One treatment-related death was observed in the combination group.尽管PFS2差异不显着，但联合治疗组的ORR和PFS优于吉非替尼单药治疗组。联合治疗组的中位OS也显着长于吉非替尼单药治疗组。联合治疗组$ 3级治疗相关不良事件（如血液学毒性）的发生率高于吉非替尼单药治疗组；生活质量没有差异。在联合组中观察到1例与治疗有关的死亡。
　　
　　4、CONCLUSION 结论。Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.与单独的吉非替尼相比，吉非替尼联合卡铂加培美曲塞可以可接受的毒性改善未经治疗的晚期NSCLC EGFR突变患者的PFS，但其OS获益尚待进一步验证。
　　
　　注：SCI 19  November 2019
　　
　　Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non–Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor
　　
　　Accepted on October 8, 2019 and published at jco.org on November 4, 2019:DOI https://doi.org/10.1200/JCO.19.01488
　　
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