奥希替尼治疗可切除突变型 NSCLC 的总生存期。
Overall Survival with Osimertinib in Resected -Mutated NSCLC.
机构信息
From the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa (M.T.), the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.) - both in Japan; the Section of Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, CT (R.S.H.); the Department of Medical Oncology, Peter MacCallum Cancer Centre, and the Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia (T.J.); the Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona (M.M.); Klinik für Pneumologie, Evangelische Lungenklinik Berlin Buch, Berlin (C.G.); Cancer Hospital, Chinese Academy of Medical Sciences, Beijing (J.W.), Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai (S.L.), and Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou (Y.-L.W.) - all in China; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.W.G.); the Department of Oncology, National Cheng Kung University, Tainan, Taiwan (W.-C.S.); the Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan (F.M.); the Department of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre (F.A.S.), and Oncology Research and Development, AstraZeneca (A.B.) - both in Toronto; the Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, South Korea (K.H.L.); Ho Chi Minh City Oncology Hospital, Binh Thanh District, Ho Chi Minh City, Vietnam (N.T.L.); the Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand (A.D.); the Department of Lung Cancer and Thoracic Tumors, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland (D.K.); and Oncology Biometrics (L.P.), and Oncology Research and Development (Y.R.), AstraZeneca, Cambridge, United Kingdom.
出版信息
N Engl J Med. 2023 Jul 13;389(2):137-147. doi: 10.1056/NEJMoa2304594. Epub 2023 Jun 4.
BACKGROUND
Among patients with resected, epidermal growth factor receptor ()-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival.
METHODS
In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety.
RESULTS
Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis.
CONCLUSIONS
Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, -mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).
背景
在接受手术切除、表皮生长因子受体 () 突变、IB 期至 IIIA 期非小细胞肺癌 (NSCLC) 治疗的患者中，与安慰剂相比，奥希替尼辅助治疗联合或不联合既往辅助化疗可显著延长无病生存期。我们报告了总体生存的计划最终分析结果。
方法
在这项 3 期、双盲试验中，我们以 1:1 的比例随机分配符合条件的患者接受奥希替尼 (80mg 每日一次) 或安慰剂治疗，直至观察到疾病复发、完成试验方案 (3 年) 或达到停药标准。主要终点是研究者评估的 II 期至 IIIA 期疾病患者的无病生存期。次要终点包括 IB 期至 IIIA 期疾病患者的无病生存期、总生存期和安全性。
结果
在接受随机分组的 682 名患者中，339 名患者接受奥希替尼治疗，343 名患者接受安慰剂治疗。在 II 期至 IIIA 期疾病患者中，奥希替尼组的 5 年总生存率为 85%，安慰剂组为 73%（总死亡风险比，0.49；95.03%置信区间 [CI]，0.33 至 0.73；P<0.001）。在总体人群（IB 期至 IIIA 期疾病患者）中，奥希替尼组的 5 年总生存率为 88%，安慰剂组为 78%（总死亡风险比，0.49；95.03%CI，0.34 至 0.70；P<0.001）。在之前公布的数据截止日期后（研究者认为该事件与试验方案无关，且患者完全康复）报告了 1 例新的与 2019 年冠状病毒病相关的肺炎严重不良事件。辅助奥希替尼的安全性与主要分析一致。
结论
在完全切除、表皮生长因子受体突变、IB 期至 IIIA 期 NSCLC 患者中，奥希替尼辅助治疗可显著提高总生存率。（由阿斯利康公司资助；ADAURA 临床试验.gov 编号，NCT02511106。）
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