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Presidential Symposium I

LBA2 - Lorlatinib vs crizotinib in the first-line treatment of patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC): Results of the phase III CROWN study


19 Sep 2020


Presidential Symposium I


Tumour Site

Non-Small Cell Lung Cancer


Benjamin Solomon


Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325


B. Solomon1, T.M. Bauer2, F. De Marinis3, E. Felip4, Y. Goto5, G. Liu6, J. Mazieres7, D. Kim8, T. Mok9, A. Polli10, H. Thurm11, A.M. Calella12, G. Peltz13, A. Shaw14

Author affiliations

  • 1 Department Of Medical Oncology, Peter MacCallum Cancer Centre, 3000 - Melbourne/AU
  • 2 Drug Development Unit, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 37203 - Nashville/US
  • 3 Division Of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan/IT
  • 4 Oncology Service, Vall d’Hebron University Hospital, 8035 - Barcelona/ES
  • 5 Department Of Thoracic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 6 Medical Oncology Department, University Health Network - Princess Margaret Cancer Center, M5G 2M9 - Toronto/CA
  • 7 Thoracic Oncology Department, Claudius Regaud Institute, 31059 - Toulouse/FR
  • 8 Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 9 Department Of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Hong Kong/HK
  • 10 Statistics Oncology, Pfizer Global Product Development, Pfizer Inc., 20152 - Milan/IT
  • 11 Pfizer Global Product Development, Pfizer Inc., La Jolla/US
  • 12 Clinical Development & Operations Gpd, Pfizer Inc., Milan/IT
  • 13 Worldwide Medical And Safety – Safety Surveillance And Risk Management, Pfizer Inc., Boston/US
  • 14 Mgh Cancer Center, Massachusetts General Hospital Cancer Center, Boston/US


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Abstract LBA2


Lorlatinib, a 3rd generation ALK tyrosine kinase inhibitor has shown overall and intracranial (IC) activity in advanced ALK+ NSCLC. We report interim data from an open label randomized, multicenter, phase III study of lorlatinib vs crizotinib in pts with untreated ALK+ NSCLC (NCT03052608).


Untreated pts with ALK+ Stage IIIB/IV NSCLC (104 study sites; 23 countries) were randomized 1:1 to oral lorlatinib (100 mg QD) or crizotinib (250 mg BID); stratified by presence of CNS metastases and ethnicity. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). PFS by investigator (INV), objective response (OR) and IC-OR by BICR, duration of response (DR), IC-DR, overall survival (OS) and safety were secondary endpoints. This planned interim analysis was conducted at 72% of 177 expected PFS events.


Of 296 pts randomized, 291 received study treatment. At data cutoff (20 March 2020), median follow-up for PFS by BICR was 18.3 months (95% CI 16.4, 20.1) for lorlatinib (n=149) and 14.8 months (95% CI 12.8, 18.4) for crizotinib (n=147). PFS by BICR was significantly prolonged with lorlatinib vs crizotinib (HR 0.28; 95% CI 0.191, 0.413; stratified 1-sided p<0.001). Lorlatinib median PFS was NE (not estimable) (95% CI NE, NE) vs crizotinib 9.3 months (95% CI 7.6, 11.1). PFS by INV, OR and IC-OR by BICR were improved with lorlatinib vs crizotinib (Table). Grade 3–4 adverse events (AE)/AEs leading to treatment discontinuation: 72.5%/6.7% for lorlatinib; 55.6%/9.2% for crizotinib. The majority of Grade 3–4 AEs for lorlatinib were laboratory abnormalities, the most common of which were lipid abnormalities. Table: LBA2

Lorlatinib (N=149) Crizotinib (N=147)
12-month PFS rate by BICR (%) 78.1 38.7
(95% CI) (70.3, 84.0) (29.8, 47.5)
Median PFS, months (95% CI) NE (NE, NE) 9.1 (7.4, 10.9)
HR (95% CI) 0.21 (0.144, 0.307)
BOR by BICR, n (%)
CR 4 (3) 0 (0)
PR 109 (73) 85 (58)
SD 19 (13) 41 (28)
Non-CR/Non-PD 3 (2) 3 (2)
Median DR, months (95% CI) NE (NE, NE) 11.0 (9.0, 12.9)
IC BOR by BICR for pts with measurable brain metastases, n (%)
Patients, n 17 13
CR 12 (71) 1 (8)
PR 2 (12) 2 (15)
SD 1 (6) 5 (39)
IC-DR*, range in months 3.9–31.4 5.4–11.1

BOR, best overall response; CR, complete response; PR, partial response; SD, stable disease, PD, progressive disease. *censored in 86% and 33% of patients, respectively.


Lorlatinib resulted in a statistically significant and clinically meaningful improvement in PFS vs crizotinib and should be considered a new first-line treatment option for pts with ALK+ NSCLC.

Clinical trial identification


Editorial acknowledgement

Medical writing support was provided by Paul O’Neill, PhD, of CMC AFFINITY, McCann Health Medical Communications, and was funded by Pfizer Inc.

Legal entity responsible for the study

Pfizer Inc.


Pfizer Inc.


B. Solomon: Advisory/Consultancy, Ad board: Pfizer; Advisory/Consultancy, Ad board: Novartis; Advisory/Consultancy, Ad board: Roche-Genentech; Advisory/Consultancy, Ad board: AstraZeneca; Advisory/Consultancy, Ad board: Bristol-Myers Squibb; Advisory/Consultancy, Ad board: Merck; Advisory/Consultancy, Ad board: Amgen; Advisory/Consultancy, Ad board: Gritstone Oncology. T.M. Bauer: Full/Part-time employment: Tennessee Oncology; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Loxo; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Ignyta; Advisory/Consultancy: Moderna Therapeutics; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: Bayer; Research grant/Funding (institution): Daiichi Sankyo; Medpacto, Inc.; Incyte; Mirati Therapeutics; MedImmune; AbbVie; AstraZeneca; Leap Therapeutics; MabVax, Stemline Therapeutics; Merck; Lilly; GlaxoSmithKline; Novartis; Pfizer; Genentech/Roche; Deciphera; Merrimack; Immunogen; Millennium; Travel/Accommodation/Expenses, Travel, accommodations, expenses: Astellas Pharma; AstraZeneca; Celgene; Clovis Oncology; EMD Serono; Genentech; Lilly; Merck; Novartis; Pharmacyclics; Sysmex; Pfizer; Advisory/Consultancy, Payment to institution for consulting services performed by Dr. Bauer: Leap Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses, Reimbursement of expenses; payment to institution for consulting services performed by Dr. Bauer: Ignyta; Moderna Therapeutics; Pfizer; Loxo; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Guardant Health; Advisory/Consultancy: Exelesis; Blueprint Medicines; Foundation Medicine; Research grant/Funding (institution): Ignyta; Calithera Biosciences; Kolltan Pharmaceuticals; Principa Biopharma; Peleton; Immunocore; Roche; Aileron Therapeutics; Bristol-Myers Squibb; Amgen; Moderna Therapeutics; Sanofi; Boehringer Ingelheim; Astellas Pharma; Five Prime Therapeutics; Research grant/Funding (institution): Jacobio; Top Alliance BioScience; Loxo; Janssen; Clovis Oncology; Takeda; Karyopharm Therapeutics; Onyx; Phosplatin Therapeutics; Foundation Medicine; Armo BioSciences. E. Felip: Advisory/Consultancy, Advisory Boards: AbbVie; AstraZeneca; Blue Print Medicines; Boehringer Ingelheim; Bristol-Myers Squibb, GSK; Eli Lilly; Guardant Health; Janssen; Medscape; Merck KGaA; Merck Sharp & Dohme; Novartis; Pfizer; Prime Oncology; Roche; Samsung; Springer; Takeda; Touchime; Speaker Bureau/Expert testimony, Board: Grífols Independent Member; Research grant/Funding (institution), Research Funding. Fundación Merck Salud; Grant For Oncology Innovation (Goi) EMD Serono. Y. Goto: Advisory/Consultancy: Eli Lilly; Chugai; Taiho Pharmaceutical; Boehringer Ingelheim; Pfizer; Novartis; AstraZeneca; GlaxoSmithKline; MSD; Guardant Health; Daiichi Sankyo; Kyorin; Chugai; Speaker Bureau/Expert testimony: Illumina; AstraZeneca; Eli Lilly; Chugai; Taiho Pharmaceutical; Boehringer Ingelheim; Ono Pharmaceutical; Bristol-Myers Squibb; Pfizer; MSD; Shionogi Pharma; Novartis; Research grant/Funding (institution): AbbVie; Eli Lilly; Taiho Pharmaceutical; Bristol Myers Squibb; Ono Pharmaceutical; Daiichi Sankyo; Pfizer; Novartis; Kyorin; Chugai; Guardant Health; Daiichi-Sankyo. G. Liu: Advisory/Consultancy, Advisory board: Pfizer; Novartis; Merck; BMS; Roche; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), Advisory board; educational rounds; research grants to institution: Takeda; AstraZeneca; Leadership role, Educational rounds: EMD Serono . J. Mazieres: Advisory/Consultancy: Roche, AstraZeneca, MSD, BMS, Pfizer, Hengrui, Daiichi, Boehringer, Pierre Fabre; Research grant/Funding (institution): Roche, AstraZeneca, Pierre Fabre. D-W. Kim: Research grant/Funding (institution): Alpha Biopharma, Astrazeneca/MedImmune, Boehringer-Ingelheim, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan; Travel/Accommodation/Expenses: Amgen, Daiichi-Sankyo. T. Mok: Research grant/Funding (institution): AstraZeneca, BMS, Clovis Oncology, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery ; Speaker Bureau/Expert testimony, Speaker's fees: ACEA Pharma; Alpha Biopharma Co., Ltd.; Amgen; Amoy Diagnostics Co., Ltd.; AstraZeneca (before 1/1/19); BI; BMS; Eli Lilly; InMed Medical Communication; MSD; Novartis; Pfizer; PrIME Oncology; Roche/Genentech; Taiho; Takeda Oncology; Honoraria (self), Honoraria/Honorarium Received (for consultation services): AbbVie Inc.; ACEA Pharma (Monthly since Aug 2018); Alpha Biopharma Co., Ltd.; Amgen; Amoy Diagnostics Co., Ltd.; AstraZeneca (before 1/1/19); Bayer; BI; Blueprint Medicines Corporation; BMS; Celgene; CStone Pharmaceuticals; Daiichi Sankyo; Eli Lilly; Honoraria (institution), Medical education/CME activities: Medscape/WebMD; Honoraria (institution), Independent medical education: PeerVoice; Honoraria (institution), Medical education: Prime Oncology; Shareholder/Stockholder/Stock options, Shareholder: Hutchison Chi-Med; Sanomics Ltd.; Shareholder/Stockholder/Stock options, Stock: Clearbridge Biomedics (now Biolidics Ltd.); Loxo-Oncology; OrigiMed Co. Ltd.; Virtus Medical Group; Advisory/Consultancy, Advisory Board: AbbVie Inc.; ACEA Pharma; Amgen; AstraZeneca; Bayer; Blueprint Medicines Corporation; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Cirina; CStone Pharmaceuticals; Daiichi Sankyo; Eli Lilly; Fishawack Facilitate Ltd.; G1 Therapeutics, Inc.; Leadership role, Board of Directors/Leadership roles (remunerated): AstraZeneca PLC; Hutchison Chi-Med; Leadership role, Board of Directors/Leadership roles (non-remunerated): American Society of Clinical Oncology (ASCO); Asian Thoracic Oncology Research Group (ATORG); Chinese Lung Cancer Research Foundation Limited (CLCRF); Honoraria (self), Honoraria/Honorarium received (for consultation services): Fishawack Facilitate Ltd.; Hengrui Therapeutics Inc; Ignyta, Inc.; Incyte Corporation; InMed Medical Communication; IQVIA; Janssen; Loxo-Oncology; Merck Serono; MSD; Honoraria (self), Honoraria/Honorarium Received (for consultation services): MoreHealth; Novartis; OncoGenex Pharmaceuticals, Inc.; OrigiMed; PeerVoice; Pfizer; PrIME Oncology; Roche/Genentech; Sanofi-Aventis R&D; SFJ Pharmaceutical Ltd.; Honoraria (self), Honoraria/Honorarium Received (for consultation services): Takeda Pharmaceuticals HK Ltd.; Vertex Pharmaceuticals; Yuhan Corporation; Advisory/Consultancy, Advisory Board: geneDecode Co., Ltd. (uncompensated); Hengrui Therapeutics Inc.; Hutchison Chi-Med; Ignyta, Inc.; Incyte Corporation; IQVIA; Janssen; Loxo-Oncology; Lunit, Inc.; Merck Serono; Merck Sharp & Dohme; Advisory/Consultancy, Advisory Board: Novartis; OncoGenex Technologies Inc.; OrigiMed; Pfizer; Roche/Genentech; Sanofi-Aventis R&D; SFJ Pharmaceutical; Takeda Oncology; Vertex Pharmaceuticals; Virtus Medical Group; Yuhan Corporation; Leadership role, Board of Directors/Leadership roles (non-remunerated): Chinese Society of Clinical Oncology (CSCO); Hong Kong Cancer Fund (HKCF); Hong Kong Cancer Therapy Society (HKCTS); International Association for the Study of Lung Cancer (IASLC) – term ended on 30/4/19; St. Stephen’s College & Prep. School. A. Polli: Full/Part-time employment, Employee: Pfizer Inc. H. Thurm: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer Inc. A.M. Calella: Full/Part-time employment: Pfizer Inc. G. Peltz: Full/Part-time employment: Pfizer Inc. A. Shaw: Honoraria (institution): Pfizer, Novartis, Genentech/Roche, Ariad/Takeda, Ignyta, Loxo, Bayer, Chugai, Blueprint Medicines, KSQ Therapeutics, Daiichi Sankyo, EMD Serono, Taiho Pharmaceutical, TP Therapeutics, Servier, Syros, Foundation Medicine, Guardant, Natera, Achilles, Archer; Travel/Accommodation/Expenses: Pfizer and Genentech; Full/Part-time employment: Novartis; Research grant/Funding (institution): Pfizer, Novartis, Roche/Genentech, Ariad, Ignyta, TP Therapeutics. All other authors have declared no conflicts of interest.

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