FDA Approves Single-Agent Nivolumab for Previously Untreated BRAF Wild-Type Advanced Melanoma
The U.S. Food and Drug Administration (FDA) today approved the programmed cell death protein 1 (PD-1) inhibitor nivolumab (Opdivo) as a single agent for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
Clinical Trial Results
The approval is based on data from the phase III CheckMate 066 trial of treatment-naive patients with unresectable or metastatic BRAF wild-type melanoma who were randomly assigned to receive nivolumab or dacarbazine. The primary endpoint of the trial was overall survival, and secondary endpoints were progression-free survival and objective response rate.
Nivolumab demonstrated superior overall survival vs chemotherapy in the first-line setting. Results were based on the analysis conducted on 47% of the total planned events for overall survival. The median overall survival was not reached for nivolumab and was 10.8 months (95% confidence interval [CI] = 9.3–12.1) in the dacarbazine arm (hazard ratio [HR] = 0.42, 95% CI = 0.30–0.60, P < .0001).
Median progression-free survival more than doubled with nivolumab: 5.1 months vs 2.2 months for patients treated with dacarbazine (HR = 0.43, 95% CI = 0.34–0.56, P < .0001). Objective response rate with nivolumab was 34% compared to 9% with dacarbazine. At the time of analysis, 88% nivolumab-treated patients had ongoing responses, which included 43 patients with ongoing responses of 6 months or longer.
Side Effects
In the trial, serious adverse reactions occurred in 36% of patients receiving nivolumab. Grade 3 and 4 adverse reactions occurred in 41% of patients receiving nivolumab, the most frequent being gamma-glutamyl transferase increase (3.9%) and diarrhea (3.4%). Adverse reactions led to permanent discontinuation of nivolumab in 7% of patients and dose interruption in 26% of patients.
The most common adverse reactions in CheckMate 066 (> 20%) reported with nivolumab vs dacarbazine were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%).
Nivolumab is associated with immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, and encephalitis; infusion reactions; and embryofetal toxicity.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
