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对艾乐替尼和克唑替尼用于未经治疗的ALK阳性非小细胞肺癌的比较研究
Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer


Solange Peters ... 肿瘤 • 2017.08.31
相关阅读
• 晚期非小细胞肺癌的精确诊断和治疗 • ASCO 2017报告——肺癌 • 克唑替尼一线治疗与化疗在ALK阳性肺癌中的疗效比较 • 克唑替尼与化疗在晚期ALK阳性肺癌中的疗效比较 • 色瑞替尼治疗ALK重排非小细胞肺癌的临床研究

摘要


背景

艾乐替尼(alectinib)是一种高度选择性的间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)抑制剂,该药在ALK阳性非小细胞肺癌(NSCLC)的治疗中已显示出全身及中枢神经系统(CNS)疗效。在既往未治疗的晚期ALK阳性NSCLC患者(包括无症状的CNS转移患者)中,我们对艾乐替尼与克唑替尼进行了比较研究。

 

方法

在一项随机、开放标签的3期试验中,我们随机分配303例既往未治疗的晚期ALK阳性NSCLC患者,分别接受艾乐替尼(600 mg,每日2次)或克唑替尼(250 mg,每日2次)治疗。主要终点是研究者评估的无进展生存期。次要终点是独立审查委员会评估的无进展生存期、至CNS进展的时间、客观有效率及总生存期。

 

结果

克唑替尼组和艾乐替尼组的中位随访期分别为17.6个月和18.6个月。在此期间,接受艾乐替尼治疗的152例患者中有62例(41%)出现疾病进展事件或者死亡,接受克唑替尼治疗的151例患者中则有102例(68%)。艾乐替尼组中研究者评估的无进展生存率显著高于克唑替尼组(12个月无事件生存率,艾乐替尼组为68.4% [95%置信区间{CI},61.0%~75.9%] vs.克唑替尼组为48.7% [95% CI,40.4%~56.9%];出现疾病进展或死亡的风险比为0.47 [95% CI,0.34~0.65];P<0.001);艾乐替尼组的中位无进展生存期尚未达到。独立审查委员会评估的无进展生存期的结果与主要终点的结果一致。艾乐替尼组共有18例患者(12%)出现CNS进展事件,克唑替尼组有68例患者(45%)出现CNS进展事件(原因特定风险比,0.16;95% CI,0.10~0.28;P<0.001)。艾乐替尼组有126例患者发生缓解(有效率,82.9%;95% CI,76%~88.5%),克唑替尼组有114例(有效率,75.5%;95% CI,67.8%~82.1%)(P=0.09)。艾乐替尼组3~5级不良事件的发生率较低(艾乐替尼组41% vs. 克唑替尼组50%)。

 

结论

与克唑替尼相比,艾乐替尼在ALK阳性NSCLC的初始治疗中显示出更好疗效和更低毒性(由霍夫曼-罗氏公司资助;ALEX在ClinicalTrials.gov注册号为NCT02075840)。





作者信息

Solange Peters, M.D., Ph.D., D. Ross Camidge, M.D., Ph.D., Alice T. Shaw, M.D., Ph.D., Shirish Gadgeel, M.D., Jin S. Ahn, M.D., Dong-Wan Kim, M.D., Ph.D., Sai-Hong I. Ou, M.D., Ph.D., Maurice Pérol, M.D., Rafal Dziadziuszko, M.D., Rafael Rosell, M.D., Ph.D., Ali Zeaiter, M.D., Emmanuel Mitry, M.D., Ph.D., Sophie Golding, M.Sc., Bogdana Balas, M.D., Johannes Noe, Ph.D., Peter N. Morcos, Pharm.D., and Tony Mok, M.D., for the ALEX Trial Investigators*
From Lausanne University Hospital, Lausanne (S.P.), and F. Hoffmann–La Roche, Basel (A.Z., E.M., S. Golding, B.B., J.N.) — both in Switzerland; University of Colorado, Denver (D.R.C.); Massachusetts General Hospital, Boston (A.T.S.); University of Michigan, Ann Arbor (S. Gadgeel); Samsung Medical Center, Sungkyunkwan University School of Medicine (J.S.A.), and Seoul National University Hospital (D.-W.K.) — both in Seoul, South Korea; Chao Family Comprehensive Cancer Center, University of California, Irvine, School of Medicine, Orange (S.-H.I.O.); Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France (M.P.); Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland (R.D.); Catalan Institute of Oncology, Barcelona (R.R.); Roche Innovation Center, New York (P.N.M.); and State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong (T.M.). Address reprint requests to Dr. Mok at the Department of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China, or at tony@clo.cuhk.edu.hk. *A complete list of the ALEX trial investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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