Adjuvant sunitinib in high-risk patients with uveal melanoma: A pilot study.

8560 Background: Uveal melanoma is the most common primary intraocular cancer in adults. Despite the successful treatments for primary tumors, up to 50% of the patients later die of distant metastases. Currently no effective adjuvant treatment is available for these patients. Our group previously reported that sunitinib stabilized systemic metastases in 65% of uveal melanoma patients who failed prior treatments. In this pilot study, we tested sunitinib in an adjuvant setting in high-risk patients with primary uveal melanoma. Methods: Patients with estimated metastatic death rate ≥ 50% based on the following criteria were eligible: (1) monosomy 3 and 8q amplification; (2) large tumor (≥ 15 mm in diameter and ≥7 mm in thickness); (3) monosomy 3 and other risk factors (large tumor, epithelioid dominant cell type, local recurrence, or extra-scleral extension). Sunitinib was given at 25 mg PO daily for at least 6 months. Primary endpoint was disease-free survival (DFS) and overall survival (OS), estimated with Kaplan-Meier analysis (SPSS 17.0). Secondary endpoint was safety. Results: A total of 23 Caucasian patients (median, 54 years; range: 25 – 77) were enrolled. All patients received sunitinib for at least 6 months (range: 6 – 12). Eighteen patients had confirmed monosomy 3, from whom 13 (72%) also showed 8q amplification. The median follow-up was 24 months (range 12 – 54 months). Only one patient died of unknown cause (OS: 30.4 months). A total of seven patients (30%) developed systemic metastases, all of which were liver metastases. The DFS and OS rates at 2 years were 70% (95% CI: 47 – 86%) and 100%, respectively. The OS rate at 2 years was better than historical control with monosomy 3 patients (51%, 95% CI: 31 – 71%) (Invest Ophthalmol Vis Sci 2003; 44:1008). In those patients who relapsed, the median time to progression after finishing sunitinib was 2 months (range: 0 – 8). The most common adverse events were: diarrhea (47%), fatigue (39%), dermatitis (30%), stomatitis (13%), leucopenia (8%), and nausea (4%). Most were grade 1 or 2 (88%) and only one was considered grade 4 (diarrhea). Conclusions: In high-risk uveal melanoma patients with estimated metastatic death rate of ≥ 50%, adjuvant sunitinib showed promising results and deserves further investigation.