Background: There is no effective systemic therapy for patients (pts) with metastatic uveal melanoma (metUvMel). Due to the paucity of clinical trials pts are frequently offered individual treatment options. We have analyzed the outcome of pts treated for metUvMel with the oral multikinase inhibitor sorafenib (S) in an IEC-approved register trial of the West German Cancer Center, a national reference center for uveal melanomas.

Methods: Pts with metUvMel were treated with S [at a dose of 400 mg bid in the first group (G1) and of 200 mg bid in the second group (G2)]. Overall survival (OS) and time to symptomatic progression (TTPsymp) were studied as primary outcome parameters. Secondary outcomes included time to radiologic progression (TTPrad) according to CT and safety. In addition, digital contrast-enhanced NMR (DCE-NMR) and contrast-enhanced ultrasound (CEUS) of liver metastases were performed in selected pts.

Results: A total of 62 pts (median age 63 yrs, range 35–83 yrs; 31 female [50%], 31 male [50%], ECOG 0 44 pts [71%], ECOG 1 15 pts [26%], ECOG 2 2 pts [3%]) were included in the analysis on an intent to treat basis (ITT). Fortysix pts had no prior systemic treatment (74%). Metastatic sites included liver in 60 pts (97%) in addition to other organs in 20 pts (32%). Only two pts (3%) had exclusively extrahepatic metastases. Following 4 CTC-Grade 4 toxicities [hand-foot-syndrome (HFS) and/or diarrhea] in the first 31 pts (G1) (13%), the starting dose of S was reduced to 200 mg twice daily in the subsequent 31 pts (G2) effectively preventing further severe side effects. Median OS was 10.8 mths (CI 6.1–15.1 mths) in G1 and 14.0 mths (CI 6.4-nd mths) in G2, median TTPrad was 5.0 mths (CI 3.1–8.9 mths) in G1 and 4,5 mths (CI 1.5–6.0 mths) in G2 and TTPsymp was 4.1 mths (CI 3.1–5.2 mths) in G1 and 7.1 mths (CI 3.2–10.6 mths) in G2 (Wilcoxon 0.043), respectively.

Conclusions: S at a dose of 200 mg bid is safe in pts with metUvMel predominantly metastatic to the liver and seems to be effective with a median OS of more than 10 mths. Treatment results are encouraging in an orphan malignant disease without established palliative systemic treatment options. A multicenter randomized discontinuation trial with S in pts with metUvMel will be performed.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C185.