Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study
Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study
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DOI：
10.1200/jco.19.01488
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发表时间：
2020-01-10
影响因子：
45.3
通讯作者：
Akai, M.
中科院分区：
文献类型：
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作者：
Hosomi, Yukio;Morita, Satoshi;Akai, M.
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治疗伴有EGFR突变的晚期非小细胞肺癌(NSCLC)疗效显著，但与单纯使用EGFR酪氨酸激酶抑制剂的标准治疗相比，其疗效和安全性尚不清楚。根据分层序贯检验方法，以无进展生存期(PFS)、无进展生存期(PFS2)和总生存期(OS)为主要终点进行序贯分析。次要终点是客观有效率(ORR)、安全性和生活质量。结果联合用药组的客观有效率和有效率均优于吉非替尼组(ORR，84%vs67%；PFS，20.9vs11.9个月；死亡或疾病进展风险比，0.490[Ptt；.001])，但Pfs2无显著差异(20.9vs18.0个月；P=.092)。联合组的中位OS也明显长于吉非替尼组(50.9vs38.8月；死亡风险比，0.722；P=.021)。联合组血液毒性等3级不良反应发生率高于吉非替尼组(65.3%vs31.0%)，生活质量差异无统计学意义。联合组观察到1例与治疗相关的死亡。结论与单用吉非替尼相比，吉非替尼联合卡铂和培美曲塞改善了未经治疗的晚期非小细胞肺癌患者的PFS，毒性可接受，尽管其对OS的益处有待进一步验证。(C)2019年美国临床肿瘤学会
PURPOSE Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced nonsmall-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. (C) 2019 by American Society of Clinical Oncology