Phase II Study of Continuous Daily Sunitinib Dosing in Patients with Previously Treated Advanced Non–Small-Cell Lung Cancer (NSCLC)

Abstract

Background Sunitinib is an oral, multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptors, platelet-derived growth factor receptors, KIT, RET, and FLT3. In a phase II trial, 11% of patients with recurrent advanced non–small-cell lung cancer (NSCLC) exhibited a partial response (PR) to sunitinib administered on a 4/2 schedule (4 weeks on treatment followed by 2 weeks off; Socinski, 2006). A planned extension of this phase II study, reported here, investigated the efficacy and safety of sunitinib given on a continuous dosing schedule. Patients and Methods Patient eligibility criteria included stage IIIB/IV NSCLC previously treated with 1-2 chemotherapy regimens, Eastern Cooperative Oncology Group performance status ≤ 1, and adequate organ function. Patients with brain metastases or recent gross hemoptysis were excluded. Treatment comprised oral sunitinib 37.5 mg per day continuously in repeated 4-week cycles. The primary endpoint was objective response rate per Response Evaluation Criteria in Solid Tumors; secondary endpoints included progression-free survival (PFS), overall survival, and safety. Results Forty-seven patients were treated on the continuous dosing schedule, starting a median of 3 cycles (range, 1-10 cycles). Baseline characteristics included median age of 60 years (range, 37-81 years); male sex, 57%; Eastern Cooperative Oncology Group performance status 0-2 (49%/49%/2%, respectively); 53% of patients had adenocarcinoma, 15% of patients had squamous cell carcinoma, and 32% of patients had “other”. One patient (2%) exhibited a PR, and 8 patients (17%) had stable disease > 3 months. Median PFS was 12.1 weeks (95% confidence interval, 8.6-13.7 weeks); median overall survival had not been reached at the time of analysis. Adverse events (AEs) were generally mild to moderate (grade 1/2) and the most common AEs were fatigue/asthenia, pain/myalgia, nausea/vomiting, diarrhea, dyspnea, and stomatitis/mucosal inflammation. Grade ≥ 3 AEs included fatigue/asthenia (15%), hypertension (6%), hypoxia (6%), dyspnea (4%), and hemoptysis (2%). Serious, treatment-related AEs included congestive heart failure (1 patient, who died after onset of this AE), gastrointestinal bleeding (n = 1), hypomagnesemia (n = 1), and hypoxic respiratory failure (n = 1). Conclusion Continuous daily sunitinib dosing has an acceptable safety profile in patients with previously treated, advanced NSCLC. Preliminary efficacy data show evidence of activity, with 1 PR and a median PFS of 12.1 weeks. Further study of sunitinib continuous dosing in combination with other treatments for NSCLC is planned.