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.
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.
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.
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.
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