MEK1/2 Inhibition in Metastatic Uveal Melanoma
In a phase III trial (SUMIT) reported in the Journal of Clinical Oncology, Carvajal et al found that the addition of the oral MEK1/2 inhibitor selumetinib to dacarbazine did not significantly improve progression-free survival in patients with metastatic uveal melanoma.
Study Details
In the double-blind trial, 129 patients with no prior systemic therapy from 29 sites in 11 countries were randomized 3:1 between April 2014 and February 2015 to receive selumetinib 75 mg twice daily plus intravenous dacarbazine 1,000 mg/m2 on day 1 of 21-day cycles (n = 97) or placebo plus dacarbazine (n = 32) until disease progression or unacceptable toxicity.
The primary endpoint was progression-free survival on blinded independent central radiologic review.
Progression-Free Survival
Median follow-up for progression-free survival was 2.7 months in the selumetinib group and 1.5 months in the placebo group. A progression-free survival event was observed in 85% vs 75% of patients; median progression-free survival was 2.8 vs 1.8 months (hazard ratio [HR] = 0.78, P = .32). Three- and 6-month rates were 38% vs 26%, and 10% vs 18%. Objective response was observed in 3% vs 0% of patients. Data on overall survival were immature, with a HR of 0.75 (P = .36) for the selumetinib vs placebo groups. Given the results of the primary progression-free survival analysis, additional analysis of overall survival is not planned.
Adverse Events
The most frequently reported adverse events of any grade for the selumetinib vs placebo groups were nausea (62% vs 19%), rash (57% vs 6%), fatigue (44% vs 47%), diarrhea (44% vs 22%), and peripheral edema (43% vs 6%). Grade ≥ 3 adverse events occurred in 63% vs 53% of patients. Serious adverse events occurred in 21% vs 6%.
The investigators concluded, “In patients with metastatic uveal melanoma, the combination of selumetinib plus dacarbazine had a tolerable safety profile but did not significantly improve [progression-free survival] compared with placebo plus dacarbazine.”
The study was supported by AstraZeneca.
Richard D. Carvajal, MD, of the Division of Hematology/Oncology at Columbia University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
