PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSION 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.

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单用吉非替尼与吉非替尼联合化疗治疗表皮生长因子受体突变的非小细胞肺癌：NEJ009 研究

目的 表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂联合细胞毒化疗对治疗 EGFR 突变的晚期非小细胞肺癌 (NSCLC) 非常有效；然而，与单独使用 EGFR-酪氨酸激酶抑制剂的标准疗法相比，这种组合的有效性和安全性知之甚少。方法 我们将 345 例新诊断的 EGFR 突变转移性 NSCLC 患者随机分配至吉非替尼联合卡铂加培美曲塞或吉非替尼单药组。根据分层顺序测试方法，将无进展生存期 (PFS)、PFS2 和总生存期 (OS) 作为主要终点进行顺序分析。次要终点是客观缓解率（ORR）、安全性和生活质量。结果 联合治疗组的 ORR 和 PFS 优于吉非替尼组（ORR，84% v 67% [P < .001]；PFS，20.9 v 11.9 个月；死亡或疾病进展的风险比，0.490 [P < .001] ])，尽管 PFS2 没有显着差异（20.9 个月对 18.0 个月；P = .092）。联合治疗组的中位 OS 也显着长于吉非替尼组（50.9 个月 vs 38.8 个月；死亡风险比，0.722；P = .021）。联合组≥ 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组（65.3% 对 31.0%）；生活质量没有差异。在联合组中观察到 1 例治疗相关死亡。结论与单独使用吉非替尼相比，