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 UnitÃ© 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.