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布加替尼与克唑替尼治疗ALK阳性非小细胞肺癌的比较
Brigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer


D. Ross Camidge ... 肿瘤 呼吸系统疾病 • 2018.11.22
相关阅读
• 布加替尼治疗ALK 阳性非小细胞肺癌

摘要


背景

布加替尼(brigatinib)是新一代间变性淋巴瘤激酶(ALK)抑制剂,对克唑替尼难治性ALK阳性非小细胞肺癌(NSCLC)患者有较强疗效。对于既往未接受过ALK抑制剂治疗的晚期ALK阳性NSCLC患者,布加替尼与克唑替尼相比疗效尚不清楚。

 

方法

在一项开放标签、3期试验中,我们以1∶1的比例,将既往未接受过ALK抑制剂治疗的晚期ALK阳性NSCLC患者随机分组,分别接受布加替尼每日1次、每次180 mg(包括7日的90 mg导入期)治疗,或者克唑替尼每日2次、每次250 mg治疗。主要终点为通过盲法、独立集中审查判定的无进展生存期。次要终点包括客观缓解率和颅内缓解。计划在198起预期疾病进展或死亡事件发生约50%后,进行第一次期中分析。

 

结果

共275例患者被随机分组;137例被分配至布加替尼组,138例被分配至克唑替尼组。第一次期中分析时(99起事件),布加替尼组和克唑替尼组的中位随访时间分别为11.0个月和9.3个月。布加替尼组的无进展生存率高于克唑替尼组(估计12个月无进展生存率,67% [95%置信区间{CI},56~75])vs. 43% [95% CI,32~53];疾病进展或死亡的风险比,0.49 [95% CI,0.33~0.74];时序检验P<0.001)。布加替尼组和克唑替尼组中经证实的客观缓解率分别为71%(95% CI,62~78)和60%(95% CI,51~68);在有可测量病变的患者中,经证实的颅内缓解率分别为78%(95% CI,52~94)和29%(95% CI,11~52)。未发现新的安全性问题。

 

结论

在既往未接受过ALK抑制剂治疗的ALK阳性NSCLC患者中,接受布加替尼治疗患者的无进展生存期显著超过接受克唑替尼治疗的患者(由阿瑞雅德制药[Ariad Pharmaceuticals]资助;ALTA-1L在ClinicalTrials.gov注册号NCT02737501)。





作者信息

D. Ross Camidge, M.D., Ph.D., Hye Ryun Kim, M.D., Ph.D., Myung-Ju Ahn, M.D., Ph.D., James Chih-Hsin Yang, M.D., Ph.D., Ji-Youn Han, M.D., Ph.D., Jong-Seok Lee, M.D., Maximilian J. Hochmair, M.D., Jacky Yu-Chung Li, M.B., B.S., Gee-Chen Chang, M.D., Ph.D., Ki Hyeong Lee, M.D., Ph.D., Cesare Gridelli, M.D., Angelo Delmonte, M.D., Ph.D., Rosario Garcia Campelo, M.D., Dong-Wan Kim, M.D., Ph.D., Alessandra Bearz, M.D., Frank Griesinger, M.D., Ph.D., Alessandro Morabito, M.D., Enriqueta Felip, M.D., Ph.D., Raffaele Califano, M.D., Sharmistha Ghosh, M.B., Ch.B., Alexander Spira, M.D., Ph.D., Scott N. Gettinger, M.D., Marcello Tiseo, M.D., Ph.D., Neeraj Gupta, Ph.D., F.C.P., Jeff Haney, M.A., David Kerstein, M.D., and Sanjay Popat, M.B., B.S., Ph.D.
From the University of Colorado Cancer Center, Aurora (D.R.C.); Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine (H.R.K.), Samsung Medical Center (M.-J.A.), and Seoul National University Hospital (D.-W.K.), Seoul, National Cancer Center, Goyang (J.-Y.H.), Seoul National University Bundang Hospital, Seongnam (J.-S.L.), and Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju (K.H.L.) — all in South Korea; National Taiwan University Hospital (J.C.-H.Y.) and the Faculty of Medicine, School of Medicine, National Yang-Ming University (G.-C.C.), Taipei, and the Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung (G.-C.C.) — all in Taiwan; the Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital, Vienna (M.J.H.); Queen Elizabeth Hospital, Kowloon, Hong Kong (J.Y.-C.L.); Azienda Ospedaliera S. Giuseppe Moscati, Avellino (C.G.), the Scientific Institute of Romagna for the Study and Treatment of Cancer, Meldola (A.D.), Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS Struttura Operativa Complessa Oncologia Medica A, Aviano (A.B.), Thoracic Medical Oncology, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples (A.M.), and the Medical Oncology Unit, University Hospital of Parma, Parma (M.T.) — all in Italy; Complejo Hospitalario Universitario de A Coruña, Coruña (R.G.C.), and Vall d’Hebron University Hospital, Barcelona (E.F.) — both in Spain; the Department of Hematology and Oncology, University Department of Internal Medicine–Oncology, Pius-Hospital Medical Campus, University of Oldenburg, Oldenburg, Germany (F.G.); the Department of Medical Oncology, Christie NHS Foundation Trust, and Division of Cancer Sciences, University of Manchester, Manchester (R.C.), and Guy’s and St. Thomas’ NHS Foundation Trust (S.G.) and Royal Marsden Hospital and the National Heart and Lung Institute, Imperial College London (S.P.), London — all in the United Kingdom; Virginia Cancer Specialists Research Institute and US Oncology Research, The Woodlands, TX (A.S.); Yale Cancer Center, New Haven, CT (S.N.G.); and Millennium Pharmaceuticals, Cambridge, MA (N.G., J.H., D.K.). Address reprint requests to Dr. Camidge at the University of Colorado Cancer Center, Anschutz Cancer Pavilion, Rm. 5327, 1665 North Aurora Ct., Aurora, CO 80045, or at ross.camidge@ucdenver.edu.

 

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