دورية أكاديمية
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
| العنوان: | 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 |
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| المؤلفون: | Blackhall, Fiona, Ross Camidge, D, Shaw, Alice T, Soria, Jean-Charles, Solomon, Benjamin J, Mok, Tony, Hirsh, Vera, Jänne, Pasi A, Shi, Yuankai, Yang, Pan-Chyr, Pas, Tommaso De, Hida, Toyoaki, Carpeño, Javier De Castro, Lanzalone, Silvana, Polli, Anna, Iyer, Shrividya, Reisman, Arlene, Wilner, Keith D, Kim, Dong-Wan |
| بيانات النشر: | BMJ Publishing Group |
| سنة النشر: | 2017 |
| المجموعة: | Harvard University: DASH - Digital Access to Scholarship at Harvard |
| مصطلحات موضوعية: | crizotinib, clinical trial, Alk, profile 1005 |
| الوصف: | 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703388/pdfTest/; ESMO Open; Blackhall, F., D. Ross Camidge, A. T. Shaw, J. Soria, B. J. Solomon, T. Mok, V. Hirsh, et al. 2017. “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.” ESMO Open 2 (3): e000219. doi:10.1136/esmoopen-2017-000219. http://dx.doi.org/10.1136/esmoopen-2017-000219Test.; http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651746Test |
| DOI: | 10.1136/esmoopen-2017-000219 |
| الإتاحة: | https://doi.org/10.1136/esmoopen-2017-000219Test http://nrs.harvard.edu/urn-3:HUL.InstRepos:34651746Test |
| رقم الانضمام: | edsbas.C38E2025 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/esmoopen-2017-000219 |
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