Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial

被引:249
作者
Camidge, D. Ross [1 ]
Kim, Hye Ryun [2 ]
Ahn, Myung-Ju [3 ]
Yang, James C. H. [4 ]
Han, Ji-Youn [5 ]
Hochmair, Maximilian J. [6 ]
Lee, Ki Hyeong [7 ]
Delmonte, Angelo [8 ]
Garcia Campelo, Maria Rosario [9 ]
Kim, Dong-Wan [10 ]
Griesinger, Frank [11 ]
Felip, Enriqueta [12 ]
Califano, Raffaele [13 ,14 ]
Spira, Alexander [15 ]
Gettinger, Scott N. [16 ]
Tiseo, Marcello [17 ]
Lin, Huamao M. [18 ]
Gupta, Neeraj [19 ]
Hanley, Michael J. [19 ]
Ni, Quanhong [19 ]
Zhang, Pingkuan [19 ]
Popat, Sanjay [20 ]
机构
[1] Univ Colorado, Canc Ctr, Anschutz Canc Pavil,1665 North Aurora Ct, Aurora, CO 80045 USA
[2] Yonsei Univ, Div Med Oncol, Dept Internal Med, Yonsei Canc Ctr,Coll Med, Seoul, South Korea
[3] Samsung Med Ctr, Seoul, South Korea
[4] Natl Taiwan Univ Hosp, Taipei, Taiwan
[5] Natl Canc Ctr, Goyang, South Korea
[6] Krankenhaus Nord Klin Floridsdorf, Dept Resp & Crit Care Med, Vienna, Austria
[7] Chungbuk Natl Univ Hosp, Cheongju, South Korea
[8] IRCCS, Ist Sci Romagnolo Studio & Cura Tumori IRST, Meldola, Italy
[9] Complejo Hosp Univ A Coruna, Coruna, Spain
[10] Seoul Natl Univ Hosp, Seoul, South Korea
[11] Carl von Ossietzky Univ Oldenburg, Pius Hosp Oldenburg, Oldenburg, Germany
[12] Vall dHebron Univ Hosp, Barcelona, Spain
[13] Univ Manchester, Christie NHS Fdn Trust, Manchester, Lancs, England
[14] Univ Manchester, Div Canc Sci, Manchester, Lancs, England
[15] Virginia Canc Specialists & US Oncol Res, The Woodlands, TX USA
[16] Yale Canc Ctr, New Haven, CT USA
[17] Univ Hosp Parma, Parma, Italy
[18] Millennium Pharmaceut Inc, Cambridge, MA USA
[19] Royal Marsden Hosp, London, England
[20] Inst Canc Res, London, England
基金
新加坡国家研究基金会;
关键词
QUALITY-OF-LIFE; EML4-ALK FUSION GENE; KINASE INHIBITOR; CHEMOTHERAPY; ALECTINIB; EFFICACY; OUTCOMES; QLQ-C30; SAFETY; EGFR;
D O I
10.1200/JCO.20.00505
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PURPOSEBrigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501). We report results of the second prespecified interim analysis (150 events).METHODSPatients with ALK inhibitor-naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected.RESULTSTwo hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank P < .0001; median, 24.0 v 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 v 9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 [95% CI, 0.49 to 1.00]; log-rank P = .049). Brigatinib daily area under the plasma concentration-time curve was not a predictor of PFS (HR, 1.005 [95% CI, 0.98 to 1.031]; P = .69).CONCLUSIONBrigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC.
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页码:3592 / +
页数:13
相关论文
共 38 条
[1]   THE EUROPEAN-ORGANIZATION-FOR-RESEARCH-AND-TREATMENT-OF-CANCER QLQ-C30 - A QUALITY-OF-LIFE INSTRUMENT FOR USE IN INTERNATIONAL CLINICAL-TRIALS IN ONCOLOGY [J].
AARONSON, NK ;
AHMEDZAI, S ;
BERGMAN, B ;
BULLINGER, M ;
CULL, A ;
DUEZ, NJ ;
FILIBERTI, A ;
FLECHTNER, H ;
FLEISHMAN, SB ;
DEHAES, JCJM ;
KAASA, S ;
KLEE, M ;
OSOBA, D ;
RAZAVI, D ;
ROFE, PB ;
SCHRAUB, S ;
SNEEUW, K ;
SULLIVAN, M ;
TAKEDA, F .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (05) :365-376
[2]  
[Anonymous], 2018, AL PACK INS
[3]  
Bazhenova LA, 2017, ANN ONCOL, V28, P479
[4]   THE EORTC QLQ-LC13 - A MODULAR SUPPLEMENT TO THE EORTC CORE QUALITY-OF-LIFE QUESTIONNAIRE (QLQ-C30) FOR USE IN LUNG-CANCER CLINICAL-TRIALS [J].
BERGMAN, B ;
AARONSON, NK ;
AHMEDZAI, S ;
KAASA, S ;
SULLIVAN, M .
EUROPEAN JOURNAL OF CANCER, 1994, 30A (05) :635-642
[5]   Patient-Reported Outcomes and Quality of Life in PROFILE 1007: A Randomized Trial of Crizotinib Compared with Chemotherapy in Previously Treated Patients with ALK-Positive Advanced Non-Small-Cell Lung Cancer [J].
Blackhall, Fiona ;
Kim, Dong-Wan ;
Besse, Benjamin ;
Nokihara, Hiroshi ;
Han, Ji-Youn ;
Wilner, Keith D. ;
Reisman, Arlene ;
Iyer, Shrividya ;
Hirsh, Vera ;
Shaw, Alice T. .
JOURNAL OF THORACIC ONCOLOGY, 2014, 9 (11) :1625-1633
[6]  
Camidge DR, 2019, J THORAC ONCOL, V14, P2023
[7]   Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer [J].
Camidge, D. R. ;
Kim, H. R. ;
Ahn, M. -J. ;
Yang, J. C. -H. ;
Han, J. -Y. ;
Lee, J. -S. ;
Hochmair, M. J. ;
Li, J. Y. -C. ;
Chang, G. -C. ;
Lee, K. H. ;
Gridelli, C. ;
Delmonte, A. ;
Garcia Campelo, R. ;
Kim, D. -W. ;
Bearz, A. ;
Griesinger, F. ;
Morabito, A. ;
Felip, E. ;
Califano, R. ;
Ghosh, S. ;
Spira, A. ;
Gettinger, S. N. ;
Tiseo, M. ;
Gupta, N. ;
Haney, J. ;
Kerstein, D. ;
Popat, S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (21) :2027-2039
[8]   Management Strategies for Early-Onset Pulmonary Events Associated with Brigatinib [J].
Camidge, D. Ross ;
Pabani, Aliyah ;
Miller, Ronni M. ;
Rizvi, Naiyer A. ;
Bazhenova, Lyudmila .
JOURNAL OF THORACIC ONCOLOGY, 2019, 14 (09) :1547-1555
[9]   Exploratory Analysis of Brigatinib Activity in Patients With Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer and Brain Metastases in Two Clinical Trials [J].
Camidge, D. Ross ;
Kim, Dong-Wan ;
Tiseo, Marcello ;
Langer, Corey J. ;
Ahn, Myung-Ju ;
Shaw, Alice T. ;
Huber, Rudolf M. ;
Hochmair, Maximilian J. ;
Lee, Dae Ho ;
Bazhenova, Lyudmila A. ;
Gold, Kathryn A. ;
Ou, Sai-Hong Ignatius ;
West, Howard L. ;
Reichmann, William ;
Haney, Jeff ;
Clackson, Tim ;
Kerstein, David ;
Gettinger, Scott N. .
JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (26) :2693-+
[10]   Constructing inverse probability weights for marginal structural models [J].
Cole, Stephen R. ;
Hernan, Miguel A. .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2008, 168 (06) :656-664