Binimetinib significantly prolonged progression-free survival compared with dacarbazine and was associated with a manageable safety profile among patients with advanced, NRAS-mutant melanoma, according to a study published in The Lancet Oncology.1
For the ongoing, international, open-label, phase 3 NEMO trial (ClinicalTrials.gov Identifier: NCT01763164), researchers evaluated the efficacy and safety of binimetinib, a MEK inhibitor, compared with dacarbazine among patients with advanced NRAS-mutant melanoma.
Investigators enrolled 402 patients with advanced, unresectable, stage IIIC or IV NRAS mutation-positive melanoma who received no prior therapy or who progressed on or after immunotherapy. Participants were randomly assigned 2:1 to receive binimetinib 45 mg orally twice daily or intravenous dacarbazine 1000 mg/m2 every 3 weeks.
Median follow-up was 1.7 months. Treatment with binimetinib reduced the risk of progression or death by 38% compared with dacarbazine (hazard ratio [HR], 0.62; 95% CI, 0.47-0.80). Median progression-free survival was 2.8 months (95% CI, 2.8-3.6) with binimetinib vs 1.5 months (95% CI, 1.5-1.7) with dacarbazine.
Among patients who received previous immunotherapy, median progression-free survival was longer for those who received binimetinib than for those who received dacarbazine (5.5 months
[95% CI, 2.8-7.6] vs 1.6 months [95% CI, 1.5-2.8], respectively).
Fifteen percent (95% CI, 11-20) of binimetinib-treated patients achieved a confirmed overall response compared with 7% (95% CI, 3-13) of those who received dacarbazine (P = .015).
There was, however, no significant difference in overall survival between the 2 treatment arms.
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About a third (34%) of binimetinib-treated patients experienced serious adverse events compared with 22% of those who received dacarbazine.
The findings suggest that binimetinib is a potential treatment strategy for patients with advanced NRAS-mutant melanoma, including those who fail previous immunotherapy.
- Dummer R, Schadendorf D, Ascierto PA, et al. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 March 8. doi: 10.1016/S1470-2045(17)30180-8 [Epub ahead of print]