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奥希替尼治疗切除术后的EGFR突变型非小细胞肺癌
Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer


Yi-Long Wu ... 肿瘤 • 2020.10.29
NEJM 动画解读

奥希替尼治疗非小细胞肺癌
相关阅读
• 奥希替尼在未经治疗的EGFR突变型晚期非小细胞肺癌中的应用 • 奥希替尼或铂类-培美曲塞治疗EGFR T790M阳性肺癌的研究

EGFR-TKI辅助治疗尘埃落定,三代药物点亮治愈之光

 

程颖

吉林省肿瘤医院

 

北京时间2020年9月20日,ADAURA研究的中枢神经系统(CNS)复发部位分析结果以Late Breaking Abstracts(LBA)形式在2020 ESMO年会公布,该研究的全文也正式在NEJM同步在线发表1。这也是继2015年AURA、2016年AURA3、2017年FLAURA和2019年FLAURA OS结果之后,奥希替尼第5次问鼎NEJM。奥希替尼在短短5年时间,迅速实现了从后线到一线,再到辅助治疗的多个角色转型,成为药物研发布局的成功典范。奥希替尼以46%的2年无病生存(DFS)率提高(90% vs. 44%;HR,0.17)的绝对优势大获全胜,也使得争议多年的靶向药物能否用于辅助治疗的问题尘埃落定。

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摘要


背景

奥希替尼是既往未经治疗的表皮生长因子受体(EGFR)突变阳性晚期非小细胞肺癌(NSCLC)的标准治疗。奥希替尼作为辅助治疗的疗效和安全性尚未明确。

 

方法

在此项双盲、3期试验中,我们以1∶1的比例将完全切除术后的EGFR突变阳性NSCLC患者随机分组,两组分别接受为期3年的奥希替尼(每日80 mg)或安慰剂治疗。主要终点是Ⅱ~ⅢA期肺癌(根据研究者的判定结果)患者的无病生存期。次要终点包括整个ⅠB~ⅢA期肺癌患者人群的无病生存期,以及总生存期和安全性。

 

结果

共计682例患者接受了随机分组(奥希替尼组339例,安慰剂组343例)。第24个月时,奥希替尼组90%(95%置信区间[CI],84~93)和安慰剂组44%(95% CI,37~51)的Ⅱ~ⅢA期肺癌患者无病生存(疾病复发或死亡的总风险比,0.17;99.06% CI,0.11~0.26;P<0.001)。在整个人群中,奥希替尼组89%(95% CI,85~92)和安慰剂组52%(95% CI,46~58)的患者在24个月时无病生存(疾病复发或死亡的总风险比,0.20;99.12% CI,0.14~0.30;P<0.001)。第24个月时,奥希替尼组98%(95% CI,95~99)和安慰剂组85%(95% CI,80~89)的患者生存且无中枢神经系统转移(疾病复发或死亡的总风险比,0.18;95% CI,0.10~0.33)。总生存期数据尚不成熟;29例患者死亡(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~ⅢA期EGFR突变阳性NSCLC患者中,奥希替尼组患者的无病生存期显著超过安慰剂组患者(由阿斯利康资助,ADAURA在ClinicalTrials.gov注册号为NCT02511106)。





作者信息

Yi-Long Wu, M.D., Masahiro Tsuboi, M.D., Jie He, M.D., Thomas John, Ph.D., Christian Grohe, M.D., Margarita Majem, M.D., Jonathan W. Goldman, M.D., Konstantin Laktionov, Ph.D., Sang-We Kim, M.D., Ph.D., Terufumi Kato, M.D., Huu-Vinh Vu, M.D., Ph.D., Shun Lu, M.D., Kye-Young Lee, M.D., Ph.D., Charuwan Akewanlop, M.D., Chong-Jen Yu, M.D., Ph.D., Filippo de Marinis, M.D., Laura Bonanno, M.D., Manuel Domine, M.D., Ph.D., Frances A. Shepherd, M.D., Lingmin Zeng, Ph.D., Rachel Hodge, M.Sc., Ajlan Atasoy, M.D., Yuri Rukazenkov, M.D., Ph.D., and Roy S. Herbst, M.D., Ph.D. for the ADAURA Investigators*
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.). Address reprint requests to Dr. Herbst at the Section of Medical Oncology, Yale School of Medicine and Yale Cancer Center, 333 Cedar St., P.O. Box 208028, New Haven, CT 06520, or at roy.herbst@yale.edu; or to Dr. Wu at the Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, and Guangdong Academy of Medical Sciences, Guangzhou, 510080, China, or at syylwu@live.cn; or to Dr. Tsuboi at the National Cancer Center Hospital East, 6 Chome-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577 Japan, or at mtsuboi@east.ncc.go.jp. *A complete list of the ADAURA investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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