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Abstract
Nivolumab 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.
We 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<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<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, 4.06; P<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.
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. (Funded by Bristol-Myers Squibb; CheckMate
066 ClinicalTrials.gov number, NCT01721772.).