D Ross Camidge1, Hye Ryun Kim1, Myung-Ju Ahn1, James Chih-Hsin Yang1, Ji-Youn Han1, Jong-Seok Lee1, Maximilian J Hochmair1, Jacky Yu-Chung Li1, Gee-Chen Chang1, Ki Hyeong Lee1, Cesare Gridelli1, Angelo Delmonte1, Rosario Garcia Campelo1, Dong-Wan Kim1, Alessandra Bearz1, Frank Griesinger1, Alessandro Morabito1, Enriqueta Felip1, Raffaele Califano1, Sharmistha Ghosh1, Alexander Spira1, Scott N Gettinger1, Marcello Tiseo1, Neeraj Gupta1, Jeff Haney1, David Kerstein1, Sanjay Popat1. 1. 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.).
Abstract
BACKGROUND: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received anALK inhibitor is unclear. METHODS: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously receivedALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred. RESULTS: A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted. CONCLUSIONS: Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501 .).
RCT Entities:
BACKGROUND:Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear. METHODS: In an open-label, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced ALK-positive NSCLC who had not previously received ALK inhibitors to receive brigatinib at a dose of 180 mg once daily (with a 7-day lead-in period at 90 mg) or crizotinib at a dose of 250 mg twice daily. The primary end point was progression-free survival as assessed by blinded independent central review. Secondary end points included the objective response rate and intracranial response. The first interim analysis was planned when approximately 50% of 198 expected events of disease progression or death had occurred. RESULTS: A total of 275 patients underwent randomization; 137 were assigned to brigatinib and 138 to crizotinib. At the first interim analysis (99 events), the median follow-up was 11.0 months in the brigatinib group and 9.3 months in the crizotinib group. The rate of progression-free survival was higher with brigatinib than with crizotinib (estimated 12-month progression-free survival, 67% [95% confidence interval {CI}, 56 to 75] vs. 43% [95% CI, 32 to 53]; hazard ratio for disease progression or death, 0.49 [95% CI, 0.33 to 0.74]; P<0.001 by the log-rank test). The confirmed objective response rate was 71% (95% CI, 62 to 78) with brigatinib and 60% (95% CI, 51 to 68) with crizotinib; the confirmed rate of intracranial response among patients with measurable lesions was 78% (95% CI, 52 to 94) and 29% (95% CI, 11 to 52), respectively. No new safety concerns were noted. CONCLUSIONS: Among patients with ALK-positive NSCLC who had not previously received an ALK inhibitor, progression-free survival was significantly longer among patients who received brigatinib than among those who received crizotinib. (Funded by Ariad Pharmaceuticals; ALTA-1L ClinicalTrials.gov number, NCT02737501 .).
Authors: Malinda Itchins; Brandon Lau; Amanda L Hudson; Helen Westman; Cathy Yi Xia; Sarah A Hayes; Viive M Howell; Michael Rodriguez; Wendy A Cooper; Heng Wei; Michael Buckland; Bob T Li; Mark Li; Vivek Rathi; Stephen B Fox; Anthony J Gill; Stephen J Clarke; Michael J Boyer; Nick Pavlakis Journal: Oncologist Date: 2020-07-02
Authors: Ethan S Srinivasan; Aaron C Tan; Carey K Anders; Ann Marie Pendergast; Dorothy A Sipkins; David M Ashley; Peter E Fecci; Mustafa Khasraw Journal: Mol Cancer Ther Date: 2021-01-05 Impact factor: 6.261