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Published on: January 25, 2015
Sorafenib as first-line therapy for metastatic uveal melanoma: A multicenter, placebo-controlled randomized
Halime Kalkavan1,2,3,4, Max E Scheulen1,2, Eckhart Kämpgen5,6
1Medical Faculty, University Duisburg-Essen, 45147 Essen, Germany.
Abstract:
Almost every second patient with uveal melanoma develops metastatic disease, with a usually fatal outcome within one year. The scarcity of broadly applicable systemic therapies further limits patient survival. In this multicenter, placebo-controlled randomized discontinuation phase 2 trial, we evaluated the efficacy of the multi-kinase inhibitor sorafenib in treatment-naïve patients with metastatic uveal melanoma (mUM). After a 56-day run-in period with 400 mg bid sorafenib in a total of 147 patients, randomization was performed in 78 patients with stable disease assigned to blinded sorafenib or placebo in a 1:1 ratio. The primary endpoint of the study was met with a significantly higher median progression-free survival (PFS) in the sorafenib group compared to placebo (5.5 vs. 1.9 months, HR = 0.53, p = 0.0083). First-line treatment with sorafenib was well tolerated and showed promising efficacy in patients with mUM. The detection of GNAQ/GNA11 mutations in ctDNA at baseline was associated with an inferior outcome. (ClinicalTrials.gov: NCT01377025).
Insights
Sorafenib, a multi-kinase inhibitor, significantly improved progression-free survival in treatment-naïve patients with metastatic uveal melanoma (mUM). This first-line therapy was well-tolerated, offering a promising option for mUM patients.
Area of Science:
- Oncology
- Medical Genetics
Background:
- Metastatic uveal melanoma (mUM) has a poor prognosis with limited systemic therapy options.
- Rapid disease progression and short survival are characteristic of mUM.
Purpose of the Study:
- To evaluate the efficacy and safety of sorafenib as a first-line treatment for patients with metastatic uveal melanoma.
- To assess the impact of GNAQ/GNA11 mutations on treatment outcomes.
Main Methods:
- A multicenter, placebo-controlled, randomized discontinuation phase 2 trial.
- 147 treatment-naïve mUM patients received sorafenib during a 56-day run-in period.
- 78 patients with stable disease were randomized 1:1 to blinded sorafenib or placebo.
Main Results:
- Sorafenib significantly increased median progression-free survival (PFS) compared to placebo (5.5 vs. 1.9 months; HR=0.53; p=0.0083).
- First-line sorafenib demonstrated promising efficacy and was well-tolerated in the mUM patient cohort.
- GNAQ/GNA11 mutations in circulating tumor DNA (ctDNA) at baseline correlated with poorer outcomes.
Conclusions:
- Sorafenib is an effective and well-tolerated first-line systemic therapy for metastatic uveal melanoma.
- The study met its primary endpoint, demonstrating a significant PFS benefit for sorafenib.
- GNAQ/GNA11 mutation status may serve as a prognostic biomarker in mUM.
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