PMID- 29209525 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240210 IS - 2059-7029 (Print) IS - 2059-7029 (Electronic) IS - 2059-7029 (Linking) VI - 2 IP - 3 DP - 2017 TI - 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. PG - e000219 LID - 10.1136/esmoopen-2017-000219 [doi] LID - e000219 AB - 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. FAU - Blackhall, Fiona AU - Blackhall F AD - Institute of Cancer Sciences, Manchester University and Christie Hospital NHS Foundation Trust, Manchester, UK. FAU - Ross Camidge, D AU - Ross Camidge D AD - Division of Oncology, University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA. FAU - Shaw, Alice T AU - Shaw AT AD - Department of Hematology/Oncology, Massachusetts General Hospital, Boston, , Massachusetts, USA. FAU - Soria, Jean-Charles AU - Soria JC AD - Department of Medical Oncology, Institut Gustave Roussy, Paris, France. FAU - Solomon, Benjamin J AU - Solomon BJ AD - Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. FAU - Mok, Tony AU - Mok T AD - State Key Laboratory of South China, Hong Kong Cancer Institute and The Chinese University of Hong Kong, Shatin, China. FAU - Hirsh, Vera AU - Hirsh V AD - Division of Medical Oncology, McGill University Health Centre, Montreal, Canada. FAU - Janne, Pasi A AU - Janne PA AD - Lowe Center for Thoracic Oncology, The Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. FAU - Shi, Yuankai AU - Shi Y AD - 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. FAU - Yang, Pan-Chyr AU - Yang PC AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Pas, Tommaso De AU - Pas T AD - Department of Oncology, European Institute of Oncology, Milan, Italy. FAU - Hida, Toyoaki AU - Hida T AD - Department of Thoracic Oncology, Aichi Cancer Center Central Hospital, Nagoya, Japan. FAU - Carpeno, Javier De Castro AU - Carpeno JC AD - Medical Oncology Service, Hospital Universitario La Paz, Madrid, Spain. FAU - Lanzalone, Silvana AU - Lanzalone S AD - Pfizer Oncology, Milan, Italy. FAU - Polli, Anna AU - Polli A AD - Pfizer Oncology, Milan, Italy. FAU - Iyer, Shrividya AU - Iyer S AD - Pfizer Oncology, New York, New York, USA. FAU - Reisman, Arlene AU - Reisman A AD - Pfizer Global Innovative Pharma Business, New York, New York, USA. FAU - Wilner, Keith D AU - Wilner KD AD - Pfizer Oncology, La Jolla, California, USA. FAU - Kim, Dong-Wan AU - Kim DW AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. LA - eng SI - ClinicalTrials.gov/NCT00932451 GR - 20465/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article DEP - 20170817 PL - England TA - ESMO Open JT - ESMO open JID - 101690685 PMC - PMC5703388 OTO - NOTNLM OT - *Alk OT - *clinical trial OT - *crizotinib OT - *profile 1005 COIS- Competing interests: We have already uploaded ICMJE form of each authors when Ann Oncol submission EDAT- 2017/12/07 06:00 MHDA- 2017/12/07 06:01 PMCR- 2017/08/17 CRDT- 2017/12/07 06:00 PHST- 2017/05/18 00:00 [received] PHST- 2017/05/29 00:00 [accepted] PHST- 2017/12/07 06:00 [entrez] PHST- 2017/12/07 06:00 [pubmed] PHST- 2017/12/07 06:01 [medline] PHST- 2017/08/17 00:00 [pmc-release] AID - S2059-7029(20)32425-X [pii] AID - esmoopen-2017-000219 [pii] AID - 10.1136/esmoopen-2017-000219 [doi] PST - epublish SO - ESMO Open. 2017 Aug 17;2(3):e000219. doi: 10.1136/esmoopen-2017-000219. eCollection 2017.