• Richard D Carvajal, Sophie Piperno-Neumann, Ellen Kapiteijn, Paul B Chapman, Stephen Frank, Anthony M Joshua, Josep M Piulats, Pascal Wolter, Veronique Cocquyt, Bartosz Chmielowski, Evans T R Jeffry TRJ Richard D. Carvajal and Gary K. Schwartz, Columbia University Medical Center; Paul B. Chapman and Alexander N. Shoushtari, Memorial Sloan Kettering C, Lauris Gastaud, Gerald Linette, Carola Berking, Jacob Schachter, Manuel J Rodrigues, Alexander N Shoushtari, Delyth Clemett, Dana Ghiorghiu, Gabriella Mariani, Shirley Spratt, Susan Lovick, Peter Barker, Elaine Kilgour, Zhongwu Lai, Gary K Schwartz, and Paul Nathan.
• Richard D. Carvajal and Gary K. Schwartz, Columbia University Medical Center; Paul B. Chapman and Alexander N. Shoushtari, Memorial Sloan Kettering Cancer Center, New York, NY; Sophie Piperno-Neumann and Manuel J. Rodrigues, Institut Curie, Paris; Lauris Gastaud, Centre Antoine-Lacassagne, Nice, France; Ellen Kapiteijn, Leiden University Medical Center, Leiden, the Netherlands; Stephen Frank, Hebrew University Hadassah Medical School - The Sharett Institute of Oncology, Jerusalem; Jacob Schachter, Sheba Medical Center at Tel Hashomer, and Tel-Aviv University Medical School, Tel Aviv, Israel; Anthony M. Joshua, Princess Margaret Cancer Centre, Toronto, ON, Canada; Josep M. Piulats, Institut Catala d'Oncologia L'Hospitalet, L'Hospitalet de Llobregat, Barcelona, Spain; Pascal Wolter, University Hospitals Leuven, Leuven, Belgium; Veronique Cocquyt, Ghent University Hospital, Ghent, Belgium; Bartosz Chmielowski, University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA; T.R. Jeffry Evans, University of Glasgow, Glasgow; Delyth Clemett, Shirley Spratt, Susan Lovick, and Elaine Kilgour, AstraZeneca, Macclesfield; Dana Ghiorghiu and Gabriella Mariani, AstraZeneca, Cambridge; Paul Nathan, Mt Vernon Cancer Centre, Northwood, United Kingdom; Gerald Linette, Washington University School of Medicine, St Louis, MO; Carola Berking, University Hospital of Munich, Munich, Germany; Peter Barker, AstraZeneca, Gaithersburg, MD; and Zhongwu Lai, AstraZeneca, Waltham, MA.
• J. Clin. Oncol. 2018 Apr 20; 36 (12): 1232-1239.

AbstractPurpose 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.

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