Final results of a pilot study using sunitinib malate in patients with stage IV uveal melanoma.

Abstract

8577 Background: The prognosis of metastatic uveal melanoma is poor; the median overall survival is reportedly less than 6 months. A significant proportion of metastatic uveal melanomas express C-kit receptors (CD117). They also produce stem cell factor. Autocrine stimulation through C-kit receptors might play a critical role in disease progression. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor of C-Kit, vascular endothelial growth factor and platelets-derived growth factor receptors; therefore, sunitinib might be effective in treatment of metastatic uveal melanoma. Methods: Patients with stage IV uveal melanoma whose metastases have at least 10% C-kit expression were treated. The initial dose of sunitinib was 37.5 mg daily over a 28-day cycle. The treatment was continued until disease progression or grade 3 or greater toxicity after dose reduction to 25 mg. The primary objectives were assessment of safety and potential efficacy of sunitinib. Clinical response was evaluated every 8 weeks using RECIST criteria; toxicity was assessed every 4 weeks. Results: Twenty patients aged 29-78 years including 17 patients who received at least one previous treatment were enrolled. One patient had partial response (PR), 12 stable diseases (SD), 5 progressive diseases (PD), and 2 non- evaluable due to withdrawal before response assessment. The clinical benefit rate (CR+PR+SD) for intent-to-treat patients was 65.5%. Median overall and progression-free survivals were 8.2 months (range 0.9-33.8 months) and 4.0 months (0.6-29.2 months), respectively. Eight patients survived more than 12 months. Three patients have no PD for more than 12 months. The most common side effect was grade 1-2 fatigue, occurring in 90% of the patients. Eleven patients required a dose reduction to 25mg due to grade 3 adverse events: diarrhea (n = 2), fatigue (n = 3), pneumonia (n = 1), neutropenia (n = 1), cardiac dysfunction (n = 1), thrombocytopenia (n = 1), hand-foot syndrome (n = 1), and headache (n = 1). Patients who needed a dose reduction were able to maintain their best response with the lower dose. Conclusions: Sunitinib at 37.5 mg daily is a feasible treatment with an acceptable safety profile and potential efficacy in metastatic uveal melanoma. No significant financial relationships to disclose.