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MEK inhibitor shows activity in NRAS-mutated melanoma
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Twenty percent of patients with NRAS-mutated melanoma treated with MEK162 demonstrated partial response, according to results of an open-label, phase 2 study.
Patients with BRAF V600 mutations have derived benefit from treatment with BRAF inhibitors. However, targeted therapies do not exist for patients with BRAF wild-type tumors, including those with NRAS mutations, according to background information provided by researchers.
Paolo Antonio Ascierto, MD, of the unit of medical oncology and innovative therapies at the National Cancer Institute in Naples, Italy, and colleagues conducted a non-randomized study to evaluate MEK162 (Novartis), a small-molecule MEK1/2 inhibitor, as a treatment for patients with NRAS- or BRAF V600-mutated melanoma.
The analysis included patients enrolled at university hospitals and private cancer centers in Europe and the United States. Patients who underwent prior treatment with BRAF inhibitors were eligible for the study, but patients who underwent prior MEK inhibitor therapy were not.
Researchers assigned patients to one of three treatment arms based on mutation status. All patients with NRAS-mutated melanoma received 45 mg twice daily. Patients with BRAF-mutated melanoma received 45 mg or 60 mg twice daily.
Study findings published in The Lancet Oncology summarized results from the two treatment arms assigned to 45 mg twice daily.
All 71 patients received at least one dose between March 31, 2011, and Jan. 17, 2012. Median follow-up was 3.3 months (range, 0.6-8.7).
No patients achieved complete response. Six of 30 patients with NRAS-mutated melanoma demonstrated partial response, three of which were confirmed. Eight of 41 patients with BRAF-mutated melanoma demonstrated partial response, two of which were confirmed.
Patients with NRAS-mutated melanoma experienced higher rates of dermatitis (60% vs. 37%), facial edema (30% vs. 17%) and creatine phosphokinase increases (37% vs. 22%), whereas patients with BRAF-mutated disease experienced higher rates of rash (39% vs. 20%), peripheral edema (34% vs. 33%) and diarrhea (37% vs. 27%), according to researchers.
The most common grade 3 or 4 adverse event was increased creatine phosphokinase, reported by 23% of patients with NRAS-mutated melanoma and 17% of those with BRAF-mutated disease. Four patients — two in each arm — experienced serious adverse events, including dehydration, diarrhea, general physical deterioration, acneiform dermatitis, small intestinal perforation and irregular heart rate, researchers wrote.
“To our knowledge, MEK162 is the first targeted therapy to show activity in patients with NRAS-mutated melanoma,” Ascierto and colleagues wrote. “[It] might offer a new option for a cancer with few effective treatments.”
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