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.
- clinical trial
- 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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