Nivolumab Prolongs Survival in Advanced, Untreated Melanoma

The PD-1 inhibitor nivolumab increased progression-free and overall survival compared with chemo in patients with previously untreated metastatic melanoma.

The PD-1 inhibitor nivolumab significantly increased overall survival compared with chemotherapy in patients with previously untreated metastatic melanoma without a BRAF mutation. In addition, the drug more than doubled the progression-free survival among these patients.

“The risk of death decreased by 58% with nivolumab, as compared with dacarbazine, among previously untreated patients with advanced melanoma,” wrote study author Caroline Robert, MD, PhD, of INSERM Unité 981, Gustave Roussy, and colleagues. “The survival benefit was consistent across all the prespecified subgroups, including patients with poor prognostic factors.”

The results of the phase III double-blind study were published in the January 22 issue of the New England Journal of Medicine.

Robert and colleagues randomly assigned 418 patients to nivolumab 3 mg/kg every 2 weeks or dacarbazine 1,000 mg/m2 every 3 weeks.

At 1 year, patients in the nivolumab group had a 58% decreased risk for death compared with patients assigned dacarbazine (hazard ratio [HR] = 0.42; 95% confidence interval [CI], 0.34–0.56; P < .001). The overall survival rate was 72.9% for nivolumab compared with 42.1% for dacarbazine.

Additionally, patients assigned the PD-1 inhibitor had a significant improvement in progression-free survival, with a median time to progression of 5.1 months compared with 2.2 months with dacarbazine treatment (HR = 0.43; 95% CI, 0.34–0.56; P < .001).

Finally, the objective response rate was 40% for patients assigned nivolumab compared with 13.9% for patients assigned dacarbazine (odds ratio [OR] = 4.06; P < .001).

Overall, treatment-related adverse events were similar between the two treatment groups (74.3% vs 75.6%), but patients treated with nivolumab reported fewer grade 3 or 4 adverse events.

The researchers noted that “because there was little difference in median overall survival between the two subgroups of dacarbazine-treated patients defined according to PD-L1 status (positive vs negative or indeterminate), the prognostic role of PD-L1 status remains to be determined.”

The US Food and Drug Administration approved nivolumab for the treatment of patients with unresectable or metastatic melanoma in December 2014.