Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT)

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, T. R.Jeffry Evans, Lauris Gastaud, Gerald Linette, Carola Berking, Jacob Schachter, Manuel J. Rodrigues, Alexander N. Shoushtari, Delyth Clemett, Dana Ghiorghiu, Gabriella MarianiShirley Spratt, Susan Lovick, Peter Barker, Elaine Kilgour, Zhongwu Lai, Gary K. Schwartz, Paul Nathan

Research output: Contribution to journalArticlepeer-review

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 comparedwith placebo plus dacarbazine.

Original languageEnglish
Pages (from-to)1232-1239
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number12
DOIs
StatePublished - 20 Apr 2018

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