A Front-Line Window of Opportunity Phase 2 Study of Sorafenib in Patients with Advanced Nonsmall Cell Lung Cancer: North Central Cancer Treatment Group Study N0326.
BACKGROUND: The current study was conducted to assess the efficacy and toxicity of sorafenib as front-line therapy in patients with stage IIIB (pleural effusion) or IV nonsmall cell lung cancer (NSCLC).
METHODS: Patients received sorafenib 400 mg twice daily by mouth continuously, and were evaluated every 2 weeks during the first 8 weeks. Patients who manifested clinical progression during this period proceeded to receive standard of care. The primary endpoint was confirmed objective tumor response. A 2-stage Fleming design was used such that if at most 1 confirmed partial response (PR) or complete response was observed in the first 20 patients (stage 1), the treatment would be considered ineffective, and further enrollment would be discontinued.
RESULTS: Only 1 PR was observed in the first 20 patients. By the time of study closure, 5 additional patients who were already being screened for study inclusion were enrolled. Of the 25 patients (15 women, 10 men; 4 stage IIIB, 21 stage IV; median age, 67 years [range, 45-85 years]), there were 3 (12%) PRs and 6 (24%) cases with stable disease observed. The median time-to-progression and progression-free survival was 2.8 months. Seven (28%) patients remained progression-free at 24 weeks. No grade 3 or higher hematologic adverse events were observed. Thirteen (52%) patients had a grade 3 nonhematologic adverse event, with fatigue (20%), diarrhea (8%), and dyspnea (8%) being the most common.
CONCLUSIONS: Sorafenib is not effective as front-line therapy in the general unselected NSCLC population. The window of opportunity design is feasible for estimating the activity of novel compounds.
Published In/Presented At
Dy, G. K., Hillman, S. L., Rowland, K. J., Molina, J. R., Steen, P. D., Wender, D. B., & ... Adjei, A. A. (2010). A Front-Line Window of Opportunity Phase 2 Study of Sorafenib in Patients with Advanced Nonsmall Cell Lung Cancer: North Central Cancer Treatment Group Study N0326. Cancer, 116(24), 5686-5693. doi:10.1002/cncr.25448
Medical Sciences | Medicine and Health Sciences
Peer Reviewed for front end display
Department of Medicine, Hematology-Medical Oncology Division, Department of Medicine Faculty