Sorafenib as first-line therapy for metastatic uveal melanoma: A multicenter, placebo-controlled randomized discontinuation study (STREAM)

Kalkavan H, Scheulen ME, Kämpgen E, Keilholz U, Heinzerling L, Lueong SS, Hlinka A, Gromke T, Ochsenreither S, Hilger RA, Grubert M, Wetter A, Guberina N, Zeschnigk M, Ferency P, Held S, Hinke A, Schuler G, Al-Ghazzawi K, Bornfeld N, Bechrakis NE, Schuler M, Bauer S, Richly H, Siveke JT (2025)


Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 28

Article Number: 114045

Journal Issue: 12

DOI: 10.1016/j.isci.2025.114045

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).

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How to cite

APA:

Kalkavan, H., Scheulen, M.E., Kämpgen, E., Keilholz, U., Heinzerling, L., Lueong, S.S.,... Siveke, J.T. (2025). Sorafenib as first-line therapy for metastatic uveal melanoma: A multicenter, placebo-controlled randomized discontinuation study (STREAM). iScience, 28(12). https://doi.org/10.1016/j.isci.2025.114045

MLA:

Kalkavan, Halime, et al. "Sorafenib as first-line therapy for metastatic uveal melanoma: A multicenter, placebo-controlled randomized discontinuation study (STREAM)." iScience 28.12 (2025).

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