A pilot study using sunitinib malate as therapy in patients with stage IV uveal melanoma

Abstract

9047 Background: In contrast to cutaneous melanoma, a significant proportion of uveal melanoma cells express c-kit (CD117). Production of stem cell factor and autocrine stimulation through c-kit receptor is considered to be one of the mechanisms for disease progression. Sunitinib malate is a multi-targeted tyrosine kinase inhibtor against vascular endothelial growth factor receptors, fms-related tyrosine kinase 3 (FLT-3), KIT, and platelet-derived growth factor receptors. Methods: Patients with stage IV uveal melanoma whose tumors have at least 10% CD 117 expression were treated. The initial dose was 37.5 mg daily over a 28 day period cycle. The treatment was continued to disease progression or grade 3 or greater toxicity after dose reduction to 25 mg daily. The primary objectives were assessment of potential clinical efficacy as well as safety of sunitinib in patients with metastatic uveal melanoma. Clinical response using RECIST criteria was evaluated every 8 weeks. Toxicity was assessed every 4 weeks. Further investigation is warranted if clinical benefit, defined as stable or regression of disease, is achieved in 50% of patients. Results: Ten patients aged 29–74 were enrolled. All but one patient failed at least one prior therapy for metastasis. Nine patients had multiple hepatic metastases. There was 1 partial response (PR), 7 stable disease (SD), and 2 progressive disease (PD). The overall clinical benefit rate was 80%. With median follow-up of 5.9 months, the median overall survival was not reached. The median progression free survival was 5.3 months. For patients who achieved PR or SD, median duration of response was 3.9 months. The most common side effect was grade 1–2 fatigue. Grade 3 adverse events included diarrhea (n=1), fatigue (n=2), pneumonia (n=1), leukopenia (n=1), cardiac dysfunction (n=1), and headache (n=1). One patient developed grade 4 thrombocytopenia. While the dose of sunitinib was decreased to 25 mg daily in 6 patients due to toxicity, these patients maintained their best response with the lowered dose. Conclusions: Sunitinib at 37.5 mg daily showed activity in patients with metastatic uveal melanoma. Sunitinib should be tested in a larger cohort of patients with uveal melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology