In metastatic melanoma, nivolumab improves overall and progression-free survival versus dacarbazine, and dabrafenib plus trametinib improves survival versus vemurafenib monotherapy, according to two studies published in the New England Journal of Medicine.

Caroline Robert, M.D., Ph.D., from Goustave Roussy and INSERM Unité 981 in Paris, and colleagues randomized 418 previously untreated patients with metastatic melanoma without a BRAF mutation to receive nivolumab and dacarbazine-matched placebo or dacarbazine and nivolumab-matched placebo.

The researchers found that the overall rate of survival at one year was 72.9 percent in the nivolumab group and 42.1 percent in the dacarbazine group (hazard ratio for death, 0.42; P < 0.001). Median progression-free survival was 5.1 and 2.2 months in the nivolumab and dacarbazine groups, respectively (hazard ratio for death or progression of disease, 0.43; P < 0.001).

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In a second study, Robert and colleagues conducted an open-label phase 3 trial involving 704 patients with metastatic melanoma with a BRAF V600 mutation. Patients were randomized to receive dabrafenib and trametinib or vemurafenib as first-line therapy.

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The researchers found that the overall survival rate at 12 months was 72 percent in the combination-therapy group versus 65 percent in the vemurafenib group (hazard ratio for death, 0.69; P = 0.005) at the preplanned interim analysis. The study was stopped for efficacy in July 2014.

The median progression-free survival was 11.4 and 7.3 months in the combination-therapy and vemurafenib groups, respectively (hazard ratio, 0.56; P < 0.001).

“The combination of dabrafenib plus trametinib was superior to vemurafenib monotherapy with regard to all efficacy end points,” the authors of the second study write.

The first study was funded by Bristol-Myers Squibb; the second study was funded by GlaxoSmithKline.


  1. Robert, Caroline, MD, PhD, et al. “Nivolumab in Previously Untreated Melanoma without BRAF Mutation.” The New England Journal of Medicine. DOI: 10.1056/NEJMoa1412082. November 16, 2014.
  2. Robert, Caroline, MD, PhD, et al. “Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametrinib.” The New England Journal of Medicine. DOI: 10.1056/NEJMoa1412690. November 16, 2014.