Phase II Trial of Sorafenib in Combination with Carboplatin and Paclitaxel in Patients with Metastatic Uveal Melanoma: SWOG S0512

Abstract

BackgroundSorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma.MethodsTwenty-five patients with stage IV uveal melanoma who had received 0–1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6) and paclitaxel (225 mg/m2) administered IV on day 1 plus sorafenib (400 mg PO twice daily), followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR); a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS).ResultsNo confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0–14%]) and the study was terminated at the first stage. Minor responses (tumor regression less than 30%) were seen in eleven of 24 (45%) patients. The median PFS was 4 months [95% CI: 1–6 months] and the 6-month PFS was 29% [95% CI: 13%–48%]. The median OS was 11 months [95% CI: 7–14 months].ConclusionIn this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients.Trial Registration ClinicalTrials.gov NCT00329641

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Management of Uveal Melanoma: A Consensus-Based Provincial Clinical Practice Guideline

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The Mayo Clinic experience with the use of kinase inhibitors, ipilimumab, bevacizumab, and local therapies in the treatment of metastatic uveal melanoma

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