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

Proceedings of the 8th International Lung Cancer Congress Abstract 09 Phase II Study of Continuous Daily Sunitinib Dosing in Patients with Previously Treated Advanced Non–Small-Cell Lung Cancer (NSCLC) G. V. Scagliotti, H. H. Gillenwater, J. R. Brahmer, R. Govindan, R. Rosell, C. P. Belani, J. N. Atkins, L. Tye, R. Chao, M. A. Socinski University of Turin, Italy; University of Virginia Health Services, Charlottesville; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Cockeysville, MD; Washington University School of Medicine, St Louis, MO; Catalan Institute of Oncology, Barcelona, Spain; University of Pittsburgh Medical Center Cancer Pavilion, PA; Southeastern Medical Oncology Center, Goldsboro, NC; Pfizer Global Research and Development, La Jolla, CA; University of North Carolina, Chapel Hill 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.

Clinical Lung Cancer July 2007

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