| Literature DB >> 29528792 |
Richard D Carvajal1, Sophie Piperno-Neumann1, Ellen Kapiteijn1, Paul B Chapman1, Stephen Frank1, Anthony M Joshua1, Josep M Piulats1, Pascal Wolter1, Veronique Cocquyt1, Bartosz Chmielowski1, T R Jeffry Evans1, Lauris Gastaud1, Gerald Linette1, Carola Berking1, Jacob Schachter1, Manuel J Rodrigues1, Alexander N Shoushtari1, Delyth Clemett1, Dana Ghiorghiu1, Gabriella Mariani1, Shirley Spratt1, Susan Lovick1, Peter Barker1, Elaine Kilgour1, Zhongwu Lai1, Gary K Schwartz1, Paul Nathan1.
Abstract
Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial ( ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m2 intravenously on day 1 of every 21-day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by blinded independent central radiologic review. Secondary end points included overall survival and objective response rate. Results A total of 129 patients were randomly assigned to receive selumetinib plus dacarbazine (n = 97) or placebo plus dacarbazine (n = 32). In the selumetinib plus dacarbazine group, 82 patients (85%) experienced a PFS event, compared with 24 (75%) in the placebo plus dacarbazine group (median, 2.8 v 1.8 months); the hazard ratio for PFS was 0.78 (95% CI, 0.48 to 1.27; two-sided P = .32). The objective response rate was 3% with selumetinib plus dacarbazine and 0% with placebo plus dacarbazine (two-sided P = .36). At 37% maturity (n = 48 deaths), analysis of overall survival gave a hazard ratio of 0.75 (95% CI, 0.39 to 1.46; two-sided P = .40). The most frequently reported adverse events (selumetinib plus dacarbazine v placebo plus dacarbazine) were nausea (62% v 19%), rash (57% v 6%), fatigue (44% v 47%), diarrhea (44% v 22%), and peripheral edema (43% v 6%). Conclusion In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had a tolerable safety profile but did not significantly improve PFS compared with placebo plus dacarbazine.Entities:
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Year: 2018 PMID： 29528792 DOI： 10.1200/JCO.2017.74.1090
Source DB: PubMed Journal: J Clin Oncol ISSN： 0732-183X Impact factor: 44.544