Interim results from an open-label, phase II trial evaluating sunitinib malate (Sutent) showed progression free survival of 9.9 weeks in non–small-cell lung cancer (NSCLC) patients with irradiated brain metastases, which occur in more than one-quarter of all NSCLC patients. These data were presented at the 13th Annual World Conference of Lung Cancer, held July 31–August 4, 2009, in San Francisco.
“We are encouraged by the antitumor activity and safety results we’re seeing with sunitinib within this patient population who continue to face a poor prognosis and increased morbidity and mortality,” said Dr. Silvia Novello, MD, PhD, Thoracic Oncology Unit, University of Turin, San Luigi Hospital, Orbassano, Italy. “These data support preclinical findings suggesting that vascular endothelial growth factor (VEGF) signaling is required for the growth of brain metastases and that small-molecule tyrosine kinase inhibitors, like sunitinib, have the ability to cross the blood brain barrier.”
Additional findings from the study show that sunitinib was well-tolerated, and there were no reports of intracranial hemorrhage. In 59 patients evaluated for safety, the most common grade 3/4 neurologic adverse events included convulsion (n = 1), mental impairment (n = 1) and peripheral motor neuropathy (n = 1). In this study, the most commonly reported treatment related grade 3/4 adverse events were fatigue (n = 5) and dyspnea (n = 6).
Sunitinib is currently approved for both gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib(Drug information on imatinib) mesylate (Gleevec), and advanced/metastatic renal cell carcinoma (RCC) based on efficacy and safety data from large, randomized phase III clinical trials.
About the Study
NSCLC patients who had previously received whole-brain radiation therapy for brain metastases and less than two prior systemic therapies were eligible to receive single-agent sunitinib (37.5 mg/d) with continuous daily dosing in a 4-week cycle. The primary study endpoint was progression-free survival (PFS).
In 53 patients evaluated for response, 12 patients experienced stable disease. As measured by Response Evaluation Criteria in Solid Tumors (RECIST), median PFS was 9.9 weeks (95% confidence interval [CI] = 7.0–13.4) and median overall survival (OS) was 19.4 weeks (95% CI = 11.4–38.6). Preliminary data measuring intracranial antitumor activity, based on World Health Organization (WHO) criteria, indicated stable disease in 26% of patients (n = 10) and progressive disease in 18% of patients (n = 7).