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
Highlights
Uveal melanoma, arising from melanocytes within the uveal tract, represents 3– 5% of all melanomas with an age-adjusted incidence of 5.1 per million [1,2,3]
We report the final results of the phase II trial of sorafenib in combination with carboplatin and paclitaxel for treatment of patients with metastatic uveal melanoma
Statistical Methods The primary objective of the study was to assess the efficacy of carboplatin and paclitaxel (CP) plus sorafenib in this patient population, as measured by the overall objective response rate (ORR) that was defined as the proportion of patients with confirmed complete or partial response
Summary
Uveal melanoma, arising from melanocytes within the uveal tract (the iris, ciliary body, and choroid of the eye), represents 3– 5% of all melanomas with an age-adjusted incidence of 5.1 per million [1,2,3]. Loco-regional therapies to the liver like radiofrequency ablation, cryoablation, chemoembolization or isolated hepatic perfusion therapy may delay the progression of hepatic metastases and may lead to palliation of cancer symptoms in selected patients [8]. The administration of these complex therapies is mostly restricted to ‘surgically-fit’ patients at major academic centers and has not shown survival benefit [9]. 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
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