From the Department of Medical Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (S.L.), the Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (X.D.), the Division of Thoracic Tumor Multimodality Treatment and Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu (M.H.), the Department of Radiotherapy, the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), the Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou (M. Chen) - all in China; the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.), the Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka (T.I.), and the Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka (T.T.) - all in Japan; the Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (M.-J.A.); the Department of Oncology, Hanoi Medical University (L.-V.Q.), and the Department of Oncology, Vietnam National Lung Hospital (D.-V.K.) - both in Hanoi; the Faculty of Medicine, Siriraj Hospital, Mahidol University (N.S.), the Division of Medical Oncology, Faculty of Medicine, Chulalongkorn University and the King Chulalongkorn Memorial Hospital (V.S.), and the Faculty of Medicine, Vajira Hospital, Navamindradhiraj University (Y.R.) - all in Bangkok, Thailand; the Division of Pulmonary Oncology and Interventional Bronchoscopy, Department of Thoracic Medicine, Linkou Chang Gung Memorial Hospital, Medical College of Chang Gung University, Taoyuan (C.-L.W.), and the Department of Oncology, National Taiwan University Hospital, and the National Taiwan University Cancer Center, Taipei (J.C.-H.Y.) - all in Taiwan; Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Málaga, Spain (M. Cobo); the Department of Internal Medicine, Division of Medical Oncology, Clinical Trial Unit, Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey (M.Ö.); Servicio Oncología, Hospital Bernardo Houssay, Mar del Plata, Buenos Aires (I.C.); Centro de Pesquisa Clínica, Centro Regional Integrado de Oncologia, Fortaleza, Brazil (E.C.); Biometrics, Late-Stage Development, Oncology Research and Development, AstraZeneca, Cambridge, United Kingdom (X.H., E.G.); Late-Stage Development, Oncology Research and Development, AstraZeneca, Baar, Switzerland (D.G.); Late-Stage Development, Oncology Research and Development, AstraZeneca, New York (T.G.); and the Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.).
N Engl J Med. 2024 Aug 15;391(7):585-597. doi: 10.1056/NEJMoa2402614. Epub 2024 Jun 2.
BACKGROUND: Osimertinib is a recommended treatment for advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor () mutation and as adjuvant treatment for resected -mutated NSCLC. EGFR tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III -mutated NSCLC. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with unresectable -mutated stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurred (as assessed by blinded independent central review) or the regimen was discontinued. The primary end point was progression-free survival as assessed by blinded independent central review. RESULTS: A total of 216 patients who had undergone chemoradiotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24; P<0.001). The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53). The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported in 48% and 38%, respectively. No new safety concerns emerged. CONCLUSIONS: Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III -mutated NSCLC. (Funded by AstraZeneca; LAURA ClinicalTrials.gov number, NCT03521154.).
背景：奥希替尼是一种推荐的治疗方法，适用于表皮生长因子受体（）突变的晚期非小细胞肺癌（NSCLC）患者，以及用于辅助治疗已切除的 -突变型 NSCLC。EGFR 酪氨酸激酶抑制剂在不可切除的 III 期 -突变型 NSCLC 中显示出初步疗效。
方法：在这项 III 期、双盲、安慰剂对照试验中，我们将未经治疗的 III 期 -突变型 NSCLC 患者随机分配，这些患者在放化疗期间或之后没有进展，接受奥希替尼或安慰剂治疗，直到疾病进展（通过盲法独立中心审查评估）或停止治疗。主要终点是盲法独立中心评估的无进展生存期。
结果：共有 216 名接受过放化疗的患者被随机分配接受奥希替尼（143 名患者）或安慰剂（73 名患者）治疗。与安慰剂相比，奥希替尼显著延长了无进展生存期：奥希替尼组的中位无进展生存期为 39.1 个月，安慰剂组为 5.6 个月，疾病进展或死亡的风险比为 0.16（95%置信区间[CI]，0.10 至 0.24；P<0.001）。奥希替尼组 12 个月时无进展且存活的患者比例为 74%（95%CI，65 至 80），安慰剂组为 22%（95%CI，13 至 32）。中期总生存数据（成熟度，20%）显示，奥希替尼组 84%的患者（95%CI，75 至 89）和安慰剂组 74%的患者（95%CI，57 至 85）存活 36 个月，死亡风险比为 0.81（95%CI，0.42 至 1.56；P=0.53）。奥希替尼组 3 级或以上不良反应发生率为 35%，安慰剂组为 12%；分别有 48%和 38%的患者出现放射性肺炎（多数为 1-2 级）。未出现新的安全问题。
结论：与安慰剂相比，奥希替尼可显著延长不可切除的 III 期 -突变型 NSCLC 患者的无进展生存期。（由阿斯利康资助；LAURA ClinicalTrials.gov 编号，NCT03521154。）
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