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奥希替尼或铂类-培美曲塞治疗EGFR T790M阳性肺癌的研究
Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer


Tony S. Mok ... 肿瘤 呼吸系统疾病 • 2017.02.16
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AURA3研究:从精准治疗向全程精准的迈进

 

周清

广东省人民医院广东省肺癌研究所,广东省医学科学院

 

表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)的发展史诠释了精准医学在肺癌诊疗实践中的价值。2009年,发表在《新英格兰医学杂志》的IPASS研究首次确立了第一代EGFR-TKI在EGFR突变型晚期非小细胞肺癌治疗中的地位,开创了肺癌精准医学步入临床实践的先河,被称为肺癌发展史上的里程碑。7年后,以Tony Mok、吴一龙教授为代表的研究团队设计开展的AUAR3研究1,将第三代EGFR-TKI奥希替尼(osimertinib)确立为EGFR突变患者出现耐药后T790M阳性之后的治疗新标准,研究结果再次发表于《新英格兰医学杂志》,标志着精准治疗向全程精准的迈进。

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摘要


背景

奥希替尼是一种表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI);该药物适用于EGFR-TKI敏感突变以及T790M耐药突变的非小细胞肺癌患者。在这些患者中,和铂类疗法联合培美曲塞相比,奥希替尼的疗效尚不清楚。

 

方法

在这项随机、国际性、开放标签的3期临床试验中,我们入组419例T790M阳性的晚期非小细胞肺癌患者;这些患者在一线EGFR-TKI治疗后出现疾病进展。我们将这些患者按照2∶1的比例分组,接受口服奥希替尼(剂量为80 mg,每日一次)治疗,或静脉给予培美曲塞(500 mg/m2)联合卡铂(目标曲线下面积为5[AUC 5])或顺铂(75 mg/m2)(每3周一次,最多6个周期);我们允许培美曲塞维持治疗。所有患者在接受一线EGFR-TKI治疗期间出现疾病进展。主要终点是研究者判定的无进展生存期。

 

结果

奥希替尼组的中位无进展生存期较铂类联合培美曲塞组显著延长(10.1个月对4.4个月;风险比0.30;95%置信区间[CI],0.23~0.41;P<0.001)。奥希替尼组的客观缓解率(71%;95% CI,65~76)显著优于铂类联合培美曲塞组(31%;95% CI,24~40)(客观缓解的比值比为5.39;95% CI,3.47~8.48;P<0.001)。在144例出现中枢神经系统(CNS)转移的患者中,接受奥希替尼治疗的患者的中位无进展生存期较铂类联合培美曲塞治疗的患者显著延长(8.5个月对4.2个月;风险比0.32;95% CI,0.21~0.49)。奥希替尼组中出现三级或更高级别不良事件的患者比例(23%)也低于铂类联合培美曲塞组(47%)。

 

结论

对于T790M阳性的晚期非小细胞肺癌患者(包括出现CNS转移的患者),其中一线EGFR-TKI治疗期间出现疾病进展的患者中,奥希替尼的疗效显著优于铂类联合培美曲塞的疗效(由阿斯利康[AstraZeneca]公司资助;AURA3在ClinicalTrials.gov注册号为NCT02151981)。





作者信息

Tony S. Mok, M.D., Yi-Long Wu, M.D., Myung-Ju Ahn, M.D., Ph.D., Marina C. Garassino, M.D., Hye R. Kim, M.D., Ph.D., Suresh S. Ramalingam, M.B., B.S., Frances A. Shepherd, M.D., Yong He, M.D., Hiroaki Akamatsu, M.D., Willemijn S.M.E. Theelen, M.D., Chee K. Lee, M.B., B.S., Ph.D., Martin Sebastian, M.D., Alison Templeton, Ph.D., Helen Mann, M.Sc., Marcelo Marotti, M.D., Ph.D., Serban Ghiorghiu, M.D., and Vassiliki A. Papadimitrakopoulou, M.D., for the AURA3 Investigators*
From the State Key Laboratory in Oncology in South China, Sir Y.K. Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong (T.S.M.), the Division of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital, and Guangdong Academy of Medical Sciences, Guangzhou (Y.-L.W.), and the Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing (Y.H.) — all in China; the Department of Medicine, Division of Hematology–Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, (M.-J.A.), and the Yonsei Cancer Center, Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine (H.R.K.), Seoul, South Korea; the Thoracic Oncology Unit, Medical Oncology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan (M.C.G.); the Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta (S.S.R.); the Department of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto (F.A.S.); the Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan (H.A.); the Department of Thoracic Oncology, the Netherlands Cancer Institute, Plesmanlaan, Amsterdam (W.S.M.E.T.); the Clinical Research Unit, Division of Cancer Services, St. George Hospital, Kogarah, NSW, Australia (C.K.L.); the Department of Hematology–Oncology, Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany (M.S.); AstraZeneca, Cambridge, United Kingdom (A.T., H.M., M.M., S.G.); and the Department of Thoracic–Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (V.A.P.). Address reprint requests to Dr. Mok at the Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China, or at tony@clo.cuhk.edu.hk. *A complete list of the AURA3 Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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