奥希替尼治疗可切除突变型非小细胞肺癌。
Osimertinib in Resected -Mutated Non-Small-Cell Lung Cancer.
机构信息
From the Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, and Guangdong Academy of Medical Sciences, Guangzhou (Y.-L.W.), the Thoracic Surgery Department, National Cancer Center-National Clinical Research Center for Cancer-Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.H.), and the Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai (S.L.) - all in China; the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa (M.T.), and the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.) - both in Japan; the Department of Medical Oncology, Austin Health, Melbourne, VIC, Australia (T.J.); the Department of Respiratory Diseases, Evangelische Lungenklinik, Berlin (C.G.); the Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona (M.M.), and the Department of Oncology, Hospital Universitario Fundación Jiménez Díaz, Madrid (M.D.); the David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J.W.G.); the Center of Innovative Technologies and Oncology, N.N. Blokhin Russian Cancer Center, Russian Academy of Medical Sciences, Moscow (K.L.); the Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine (S.-W.K.), and the Precision Medicine Lung Cancer Center, Konkuk University Medical Center (K.-Y.L.) - both in Seoul, South Korea; the Department of Thoracic Surgery, Cho Ray Hospital, Ho Chi Minh City, Vietnam (H.-V.V.); the Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand (C.A.); the Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-J.Y.); the Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan (F.M.), and Medical Oncology 2, Istituto Oncologico Veneto, IRCCS, Padua (L.B.) - both in Italy; the Department of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre and the University of Toronto, Toronto (F.A.S.); Late Oncology Statistics, AstraZeneca, Gaithersburg, MD (L.Z.); Late Oncology Statistics (R.H.) and Oncology Research and Development (A.A., Y.R.), AstraZeneca, Cambridge, United Kingdom; and Section of Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, CT (R.S.H.).
出版信息
N Engl J Med. 2020 Oct 29;383(18):1711-1723. doi: 10.1056/NEJMoa2027071. Epub 2020 Sep 19.
BACKGROUND
Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor () mutation-positive advanced non-small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown.
METHODS
In this double-blind, phase 3 trial, we randomly assigned patients with completely resected mutation-positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety.
RESULTS
A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P<0.001). In the overall population, 89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33). Overall survival data were immature; 29 patients died (9 in the osimertinib group and 20 in the placebo group). No new safety concerns were noted.
CONCLUSIONS
In patients with stage IB to IIIA mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).
背景
奥希替尼是标准治疗方法，用于治疗未经治疗的表皮生长因子受体（EGFR）突变阳性的晚期非小细胞肺癌（NSCLC）。奥希替尼作为辅助治疗的疗效和安全性尚不清楚。
方法
在这项双盲、III 期临床试验中，我们将完全切除的 EGFR 突变阳性 NSCLC 患者以 1:1 的比例随机分配，接受奥希替尼（80mg 每日一次）或安慰剂治疗 3 年。主要终点是 II 期至 IIIA 期疾病（研究者评估）患者的无病生存期。次要终点包括 IB 期至 IIIA 期疾病患者的总体人群无病生存期、总生存期和安全性。
结果
共有 682 名患者接受了随机分组（奥希替尼组 339 例，安慰剂组 343 例）。在 24 个月时，奥希替尼组 II 期至 IIIA 期疾病患者的 90%（95%置信区间[CI]，84 至 93）和安慰剂组的 44%（95%CI，37 至 51）存活且无疾病（疾病复发或死亡的总体风险比，0.17；99.06%CI，0.11 至 0.26；P<0.001）。在总体人群中，奥希替尼组 89%（95%CI，85 至 92）和安慰剂组 52%（95%CI，46 至 58）的患者在 24 个月时存活且无疾病（疾病复发或死亡的总体风险比，0.20；99.12%CI，0.14 至 0.30；P<0.001）。在 24 个月时，奥希替尼组 98%（95%CI，95 至 99）和安慰剂组 85%（95%CI，80 至 89）的患者存活且无中枢神经系统疾病（疾病复发或死亡的总体风险比，0.18；95%CI，0.10 至 0.33）。总生存数据不成熟；29 名患者死亡（奥希替尼组 9 例，安慰剂组 20 例）。未发现新的安全性问题。
结论
在 IB 期至 IIIA 期 EGFR 突变阳性 NSCLC 患者中，接受奥希替尼治疗的患者无病生存期明显长于接受安慰剂治疗的患者。（由阿斯利康公司资助；ADAURA 临床试验.gov 编号，NCT02511106。）
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