Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: A phase III, multicenter, randomized trial (SUMIT) Journal Article

Authors: Carvajal, R. D.; Piperno-Neumann, S.; Kapiteijn, E.; Chapman, P. B.; Frank, S.; Joshua, A. M.; Piulats, J. M.; Wolter, P.; Cocquyt, V.; Chmielowski, B.; Evans, T. R. J.; Gastaud, L.; Linette, G.; Berking, C.; Schachter, J.; Rodrigues, M. J.; Shoushtari, A. N.; Clemett, D.; Ghiorghiu, D.; Mariani, G.; Spratt, S.; Lovick, S.; Barker, P.; Kilgour, E.; Lai, Z.; Schwartz, G. K.; Nathan, P.
Article Title: Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: A phase III, multicenter, randomized trial (SUMIT)
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 ( 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. © 2018 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 36
Issue: 12
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2018-04-20
Start Page: 1232
End Page: 1239
Language: English
DOI: 10.1200/jco.2017.74.1090
PROVIDER: scopus
PUBMED: 29528792
Notes: Conference Paper -- Export Date: 1 May 2018 -- Source: Scopus
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  1. Paul Chapman
    240 Chapman