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
Fiona Blackhall, D Ross Camidge, Alice T Shaw, Jean-Charles Soria, Benjamin J Solomon, Tony Mok, Vera Hirsh, Pasi A Jänne, Yuankai Shi, Pan-Chyr Yang, Tommaso De Pas, Toyoaki Hida, Javier De Castro Carpeño, Silvana Lanzalone, Anna Polli, Shrividya Iyer, Arlene Reisman, Keith D Wilner, Dong-Wan Kim, Fiona Blackhall, D Ross Camidge, Alice T Shaw, Jean-Charles Soria, Benjamin J Solomon, Tony Mok, Vera Hirsh, Pasi A Jänne, Yuankai Shi, Pan-Chyr Yang, Tommaso De Pas, Toyoaki Hida, Javier De Castro Carpeño, Silvana Lanzalone, Anna Polli, Shrividya Iyer, Arlene Reisman, Keith D Wilner, Dong-Wan Kim
Abstract
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.
Keywords: Alk; clinical trial; crizotinib; profile 1005.
Conflict of interest statement
Competing interests: We have already uploaded ICMJE form of each authors when Ann Oncol submission
Figures
References
- Christensen JG, Zou HY, Arango ME, et al. . Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol Cancer Ther 2007;6:3314–22. 10.1158/1535-7163.MCT-07-0365
- Camidge DR, Bang YJ, Kwak EL, et al. . Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol 2012;13:1011–9. 10.1016/S1470-2045(12)70344-3
- Kim DW, Ahn M-J, Shi Y, et al. , 2012. Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell Lung Cancer (NSCLC) (Poster), American Society of clinical oncology (ASCO) 48th Annual Meeting, Chicago Abstract 7533.
- Ou SH, Bartlett CH, Mino-Kenudson M, et al. . Crizotinib for the treatment of ALK-rearranged non-small cell lung cancer: a success story to usher in the second decade of molecular targeted therapy in oncology. Oncologist 2012;17:1351–75. 10.1634/theoncologist.2012-0311
- Shaw AT, Kim DW, Nakagawa K, et al. . Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368:2385–94. 10.1056/NEJMoa1214886
- Solomon BJ, Mok T, Kim DW, et al. . First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014;371:2167–77. 10.1056/NEJMoa1408440
- Chun SG, Iyengar P, Gerber DE, et al. . Optic neuropathy and blindness associated with crizotinib for non-small-cell lung cancer with EML4-ALK translocation. J Clin Oncol 2015;33:e25–e26. 10.1200/JCO.2013.49.1985
- Osoba D, Rodrigues G, Myles J, et al. . Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 1998;16:139–44. 10.1200/JCO.1998.16.1.139
- Salgia R, Solomon BJ, Shaw AT, et al. . Visual effects in anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) patients treated with crizotinib. ASCO Meeting Abstracts 2012;30:7596.
- Schnell P, Bartlett CH, Solomon BJ, et al. . Complex renal cysts associated with crizotinib treatment. Cancer Med 2015;4:887–96. 10.1002/cam4.437
- Iyer S, Roughley A, Rider A, et al. . The symptom burden of non-small cell lung cancer in the USA: a real-world cross-sectional study. Support Care Cancer 2014;22:181–7. 10.1007/s00520-013-1959-4
- LeBlanc TW, Nickolich M, Rushing CN, et al. . What bothers lung cancer patients the most? A prospective, longitudinal electronic patient-reported outcomes study in advanced non-small cell lung cancer. Support Care Cancer 2015;23:3455–63. 10.1007/s00520-015-2699-4
Source: PubMed