Nivolumab ( Opdivo ) was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with Ipilimumab-refractory metastatic melanoma.
The use of Nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study.
Researchers randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive Nivolumab ( at a dose of 3 mg per kilogram of body weight every 2 weeks and Dacarbazine-matched placebo every 3 weeks ) or Dacarbazine ( at a dose of 1000 mg per square meter of body-surface area every 3 weeks and Nivolumab-matched placebo every 2 weeks ).
The primary end point was overall survival.
At 1 year, the overall rate of survival was 72.9% ( 95% confidence interval [CI], 65.5 to 78.9 ) in the Nivolumab group, as compared with 42.1% ( 95% CI, 33.0 to 50.9 ) in the Dacarbazine group ( hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P less than 0.001 ).
The median progression-free survival was 5.1 months in the Nivolumab group versus 2.2 months in the Dacarbazine group ( hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P less than 0.001 ).
The objective response rate was 40.0% ( 95% CI, 33.3 to 47.0 ) in the Nivolumab group versus 13.9% ( 95% CI, 9.5 to 19.4 ) in the Dacarbazine group ( odds ratio, OR=4.06; P less than 0.001 ).
The survival benefit with Nivolumab versus Dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 ( PD-L1 ).
Common adverse events associated with Nivolumab included fatigue, pruritus, and nausea. Drug-related adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with Nivolumab and 17.6% of those treated with Dacarbazine.
In conclusion, Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with Dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. ( Xagena )
Robert C et al, N Engl J Med 2015;372:320-330