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 Cancer 2010 116 5686-93 (C) 2010 American Cancer Society