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Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer
  1. Fiona Blackhall1,
  2. D Ross Camidge2,
  3. Alice T Shaw3,
  4. Jean-Charles Soria4,
  5. Benjamin J Solomon5,
  6. Tony Mok6,
  7. Vera Hirsh7,
  8. Pasi A Jänne8,
  9. Yuankai Shi9,
  10. Pan-Chyr Yang10,
  11. Tommaso De Pas11,
  12. Toyoaki Hida12,
  13. Javier De Castro Carpeño13,
  14. Silvana Lanzalone14,
  15. Anna Polli14,
  16. Shrividya Iyer15,
  17. Arlene Reisman16,
  18. Keith D Wilner17,
  19. Dong-Wan Kim18
  1. 1 Institute of Cancer Sciences, Manchester University and Christie Hospital NHS Foundation Trust, Manchester, UK
  2. 2 Division of Oncology, University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA
  3. 3 Department of Hematology/Oncology, Massachusetts General Hospital, Boston, , Massachusetts, USA
  4. 4 Department of Medical Oncology, Institut Gustave Roussy, Paris, France
  5. 5 Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
  6. 6 State Key Laboratory of South China, Hong Kong Cancer Institute and The Chinese University of Hong Kong, Shatin, China
  7. 7 Division of Medical Oncology, McGill University Health Centre, Montreal, Canada
  8. 8 Lowe Center for Thoracic Oncology, The Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
  9. 9 Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  10. 10 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  11. 11 Department of Oncology, European Institute of Oncology, Milan, Italy
  12. 12 Department of Thoracic Oncology, Aichi Cancer Center Central Hospital, Nagoya, Japan
  13. 13 Medical Oncology Service, Hospital Universitario La Paz, Madrid, Spain
  14. 14 Pfizer Oncology, Milan, Italy
  15. 15 Pfizer Oncology, New York, New York, USA
  16. 16 Pfizer Global Innovative Pharma Business, New York, New York, USA
  17. 17 Pfizer Oncology, La Jolla, California, USA
  18. 18 Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
  1. Correspondence to Dr Dong-Wan Kim; kimdw{at}


Purpose Crizotinib is a potent, orally administered tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). We report final results from PROFILE 1005, the largest clinical trial to date for an ALK inhibitor in ALK-positive NSCLC.

Patients and methods PROFILE 1005 (NCT00932451) was a multicenter, single-arm phase 2 trial of the efficacy, safety and tolerability of crizotinib (250 mg twice daily; 3 week continuous treatment cycles) in patients with ALK-positive NSCLC after failure of ≥1 lines of systemic treatment for locally advanced/metastatic disease. Patients’ tumour ALK status was initially determined by a central laboratory until a protocol amendment permitted enrolment of patients based on locally determined ALK status. Co-primary endpoints were objective response rate (ORR), evaluated using Response Evaluation Criteria in Solid Tumours V.1.1 and adverse events (AEs). Cancer-specific patient-reported outcomes (PROs) were also assessed using the European Organisation for the Research and Treatment of Cancer QLQ-C30 and its lung cancer module QLQ-LC13.

Results 1069 patients were enrolled; 1066 received crizotinib. The as-treated population comprised 908 and 158 patients, in whom tumour positive ALK-status was determined centrally (± locally) or locally only, respectively. At baseline, a majority of patients were <65 years (84%), 66% were never smokers and 46% were Asian. Derived investigator-assessed ORR was 54% (95% CI 51 to 57) and 41% (95% CI 33 to 49) in the central-testing and local-testing subgroups, respectively. The most common treatment-related AEs in the overall population (any grade) were vision disorder (58%), nausea (51%), diarrhoea (47%) and vomiting (47%). PRO scores demonstrated clinically meaningful improvement in lung cancer symptoms and global quality of life.

Conclusion The efficacy, safety and PRO profiles of crizotinib in this cohort of 1066 patients with ALK-positive NSCLC are consistent with previous reports.

Trial registration number Phase 2 trial (NCT00932451); Results.

  • crizotinib
  • clinical trial
  • Alk
  • profile 1005

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  • Contributors We confirm that all authors made substantial contributions to the concept and design or analysis and interpretation of data and to the drafting of the manuscript or revising it critically for important intellectual content. Editorial support was provided by Wendy Sacks and Kayleigh Bassiri at ACUMED (New York, New York, USA), an Ashfield Company, part of UDG Healthcare and by Claire Clowes and Simon Lancaster at inScience Communications (Chester, UK) and was funded by Pfizer. This article has not been published elsewhere, nor is it under consideration for publication by another journal.

  • Funding Pfizer, Inc

  • Competing interests We have already uploaded ICMJE form of each authors when Ann Oncol submission

  • Patient consent Obtained.

  • Ethics approval The institutional review board or independent ethics committee at each participating centre approved the protocol, which complied with the International Ethical Guidelines for Biomedical Research Involving Human Subjects, Good Clinical Practice guidelines, the Declaration of Helsinki and local laws.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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