Selumetinib Plus Dacarbazine Does Not Improve Uveal Melanoma Outcomes

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Researchers randomly assigned 129 patients with previously untreated metastatic uveal melanoma to receive dacarbazine plus selumetinib or placebo.
Researchers randomly assigned 129 patients with previously untreated metastatic uveal melanoma to receive dacarbazine plus selumetinib or placebo.

Adding selumetinib to dacarbazine did not improve progression-free survival (PFS) among patients with previously untreated metastatic uveal melanoma, according to results from the SUMIT trial published in the Journal of Clinical Oncology.1

The RAS/RAF/MEK/ERK pathway is constitutively active in over 80% of uveal melanomas. The purpose of this study was to determine if the addition of selumetinib, a potent and highly selective inhibitor of MEK1/2, to dacarbazine could improve outcomes.

The double-blind phase 3 SUMIT trial (ClinicalTrials.gov Identifier: NCT01974752) randomly assigned 129 patients with previously untreated metastatic uveal melanoma 3:1 to receive dacarbazine plus selumetinib or placebo. The median age at baseline was 63 (range, 2-86) in the selumetinib group and 58 (range, 42-84) in the placebo group.

The primary endpoint was similar between groups, with a median PFS of 2.8 months with selumetinib compared with 1.8 months with placebo (hazard ratio [HR], 0.78; 95% CI, 0.48-1.27; P = .32), regardless of sex, histology/tumor grade, or GNA11 or GNAQ positivity.

A preliminary analysis of overall survival also demonstrated no difference between the selumetinib and placebo groups (HR, 0.75; 95% CI, 0.39-1.46; P = .40). The overall response was also similar, at 3% with selumetinib vs 0% with placebo (P = .36).

Few patients discontinued selumetinib because of adverse events (AEs), and most AEs were of grade 1/2. Common AEs of special interest that occurred more frequently in the experimental arm included nausea, rash, diarrhea, peripheral edema, dermatitis acneiform, and hypertension.

Though the selumetinib plus dacarbazine combination did not improve efficacy in this study, the authors noted that MEK inhibitors should continue to be studied in this disease because “it remains a possibility that dacarbazine limits the efficacy of MEK inhibitors in this disease, and the exploration of selumetinib as monotherapy or in alternative combinations, other than with alkylating agents, remains of interest.”

Reference

  1. Carvajal RD, Piperno-Neumann S, Kapiteijn E, et al. Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicenter, randomized trial (SUMIT). J Clin Oncol. 2018 Mar 12. doi: 10.1200/JCO.2017.74.1090 [Epub ahead of print]

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