Brigatinib versus Crizotinib in ALK Inhibitor–Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial

    Published:October 14, 2022DOI:
        D. Ross Camidge,a Hye-Ryun Kim,b Myung-Ju Ahn,c James CH Yang,d Ji-Youn Han,e Maximilian J Hochmair,f Ki Hyeong Lee,g Angelo Delmonte,h Maria Rosario Garcia Campelo,i Dong-Wan Kim,j Frank Griesinger,k Enriqueta Felip,l Raffaele Califano,m Alexander I. Spira,n Scott N. Gettinger,o Marcello Tiseo,p Huamao M. Lin,q Yuyin Liu,q Florin Vranceanu,q Huifeng Niu,q Pingkuan Zhang,q Sanjay Popatr
        a University of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO, USA 80045; [email protected]
        b Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
        c Samsung Medical Center, Seoul, South Korea
        d National Taiwan University Cancer Center, Taipei, Taiwan
        e National Cancer Center, Goyang, South Korea
        f Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Vienna, Austria
        g Chungbuk National University Hospital, Cheongju, South Korea
        h Scientific Institute of Romagna for the Study and Treatment of Cancer, Meldola, Italy
        i University Hospital A Coruña, CHUAC, A Coruña, Spain
        j Seoul National University Hospital, Seoul, South Korea
        k Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Germany
        l Vall d'Hebron University Hospital, Barcelona, Spain
        m The Christie NHS Foundation Trust, Manchester, England, United Kingdom
        n Virginia Cancer Specialists and US Oncology Research, The Woodlands, TX, USA
        o Yale Cancer Center, New Haven, CT, USA
        p University Hospital of Parma, Parma, Italy
        q Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA
        r Royal Marsden Hospital, 203 Fulham Road, Chelsea, London, England, United Kingdom SW3 6JJ; [email protected]
        Address for correspondence: D. Ross Camidge, Professor of Medicine/Oncology, University of Colorado Cancer Center, 1665 Aurora Court, Aurora, CO 80045, Phone: 720-848-0449, Fax: 720-848-0465, E-mail: [email protected]
        Following publication of our article, we discovered three errors in data reported in two manuscript figures. In Figure 1F, the 3-year probability of intracranial PFS in the brigatinib arm was incorrectly reported as 56% due to a rounding error and should instead be 57%. The data were correctly reported in the manuscript body. In addition, the number of patients at risk at 36 months in the brigatinib arm was incorrectly reported as 53 but should be 51. In Figure 2A, the p value for the HR for death, 0.305, was incorrectly reported in place of the log-rank p value, 0.3311. The log-rank p value was correctly reported in the manuscript body. Revised figures reflect the described corrections.
        These errors do not alter the conclusion of the manuscript that brigatinib continued to demonstrate superior efficacy over crizotinib as first-line treatment for patients with advanced ALK+ NSCLC, consistent with two interim analyses.

        Conflicts of interest

        - D Ross Camidge: Honoraria (AstraZeneca, Takeda, Arrys/Kyn, Genoptix, G1 Therapeutics (DSMB), Mersana Therapeutics, Roche/Genentech, Ignyta, Daiichi Sankyo (ILD adjudication committee), Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med, Orion, Clovis, Celgene, Novartis); research funding (ARIAD/Takeda)
        - Hye-Ryun Kim: Honoraria, consulting or advisory role (AstraZeneca, Roche, Boehringer Ingelheim)
        - Myung-Ju Ahn: Honoraria (AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis), consulting or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis)
        - James CH Yang: Honoraria or advisory role (Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceutical, Daiichi Sankyo, Takeda, AstraZeneca, Hansoh Pharmaceuticals)
        - Ji-Youn Han: Research funding (Roche)
        - Maximilian J Hochmair: Honoraria (AstraZeneca, BMS, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, Takeda), consulting or advisory role (Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Roche, Takeda)
        - Ki Hyeong Lee: Honoraria, advisory role (AstraZeneca, Eli Lilly, Boehringer Ingelheim)
        - Angelo Delmonte: Consulting/advisory role (AstraZeneca, Boehringer Ingelheim)
        - Maria Rosario Garcia Campelo: Consulting/advisory role (Takeda, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim, Pfizer, Janssen, Eli Lilly)
        - Dong-Wan Kim: Research funding (all to institution: Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge BioTherapeutics, GSK), travel/accommodations (Amgen, Daiichi Sankyo)
        - Frank Griesinger: Consulting or advisory role (ARIAD, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Siemens, Amgen, GSK, Janssen)
        - Enriqueta Felip: Consulting/advisory role (AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Guardant Health, MSD, Novartis, Pfizer, Roche, Takeda, Merck)
        - Raffaele Califano: Honoraria and consulting or advisory role (AstraZeneca, BMS, Roche, MSD, Boehringer Ingelheim, Takeda, Novartis)
        - Alexander Spira: Consulting/advisory role (ARIAD, AstraZeneca, Clovis Oncology, Roche, Amgen, Mirati, BMS, Merck)
        - Scott N Gettinger: Consulting or advisory role (ARIAD, BMS, Janssen), research funding (ARIAD, AstraZeneca/MedImmune, BMS, Boehringer Ingelheim, Incyte, Pfizer, Roche/Genentech)
        - Marcello Tiseo: Speakers bureau or advisory role (AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Roche)
        - Huamao M Lin: Employment (Takeda)
        - Yuyin Liu: Employment (Takeda)
        - Florin Vranceanu: Employment (Takeda)
        - Huifeng Niu: Employment (Takeda)
        - Pingkuan Zhang: Employment (Takeda)
        - Sanjay Popat: Advisory board (Amgen, AstraZeneca, Bayer, BeiGene, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Guardant Health, Janssen, Lilly, Merck KGaA, Novartis, Roche, Takeda; sub-investigator (Amgen, MSD [all to institution]); coordinating PI (Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics [all to institution]); local PI (AstraZeneca, GSK, Roche, Trizel [all to institution]); advisory role (ALK Positive UK, International Association for the Study of Lung Cancer, Lung Cancer Europe, Ruth Strauss Foundation); leadership role (British Thoracic Oncology Group, European Thoracic Oncology Platform); officer (European Society of Medical Oncology); member of Board of Directors (Mesothelioma Applied Research Foundation)

        Funding Statement

        This study was sponsored by ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

        Data Sharing Statement

        The data sets, including the redacted study protocol, redacted statistical analysis plan, and individual participant data supporting the results reported in this article, will be made available within three months from initial request, to researchers who provide a methodologically sound proposal. The data will be provided after de-identification, in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization.
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        The authors would like to thank the patients, their families, and their caregivers; the ALTA-1L investigators and their team members at each study site; and colleagues from ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD and Lela Creutz, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Millennium Pharmaceuticals, Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. We thank Teodor G. Paunescu, PhD (Millennium Pharmaceuticals), for editorial assistance.

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