Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT). Academic Article uri icon

Overview

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.

authors

  • Carvajal, Richard D
  • Piperno-Neumann, Sophie
  • Kapiteijn, Ellen
  • Chapman, Paul
  • Frank, Stephen
  • Joshua, Anthony M
  • Piulats, Josep M
  • Wolter, Pascal
  • Cocquyt, Veronique
  • Chmielowski, Bartosz
  • Evans, T R Jeffry
  • Gastaud, Lauris
  • Linette, Gerald
  • Berking, Carola
  • Schachter, Jacob
  • Rodrigues, Manuel J
  • Shoushtari, Alexander N
  • Clemett, Delyth
  • Ghiorghiu, Dana
  • Mariani, Gabriella
  • Spratt, Shirley
  • Lovick, Susan
  • Barker, Peter
  • Kilgour, Elaine
  • Lai, Zhongwu
  • Schwartz, Gary K
  • Nathan, Paul

publication date

  • March 12, 2018

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Melanoma
  • Uveal Neoplasms

Identity

Scopus Document Identifier

  • 85045683841

Digital Object Identifier (DOI)

  • 10.1200/JCO.2017.74.1090

PubMed ID

  • 29528792

Additional Document Info

volume

  • 36

issue

  • 12