In a phase II trial (EBIN) reported in The Lancet Oncology, Robert et al investigated the survival benefit of adding induction encorafenib/binimetinib to nivolumab/ipilimumab in patients with advanced melanoma with BRAF V600E or BRAF V600K mutation.
Study Details
In the open-label trial, 271 patients from sites in eight European countries who had previously untreated, unresectable, stage III or IV melanoma with BRAF V600E or BRAF V600K mutation were randomly assigned between November 2018 and July 2022 to receive induction targeted therapy with encorafenib/binimetinib followed by nivolumab/ipilimumab (n = 136) or nivolumab/ipilimumab without induction (n = 135). Treatment in the induction group consisted of encorafenib at 450 mg once daily plus binimetinib at 45 mg twice daily for 12 weeks followed by nivolumab at 3 mg/kg plus ipilimumab at 1 mg/kg once every 3 weeks for four doses and then nivolumab at 480 mg every 4 weeks until disease progression, unacceptable toxicity, or 2 years. The control group received nivolumab/ipilimumab on the same schedule. The primary outcome measure was progression-free survival.
Key Findings
Median follow-up was 21 months (interquartile range = 13–33 months). Median progression-free survival was 9 months (95% confidence interval [CI] = 7–13 months) in the induction group vs 9 months (95% CI = 5–14 months) in the control group (hazard ratio [HR] = 0.87, 90% CI = 0.67–1.12, P = .36). Rates at 12 weeks, 6 months, and 2 years were 99% vs 73%, 62% vs 56%, and 29% vs 35%, respectively.
Objective responses were observed in 53% of the induction group vs 45% of the control group, including complete responses in 12% vs 10%, respectively.
Grade 3 to 5 treatment-related adverse events were reported in 42% of the induction group vs 32% of the control group. The most common of these events were hepatitis (13%) and increased transaminases (8%) in the induction group and hepatitis (7%) and increased lipase (6%) in the control group. Serious treatment-related adverse events occurred in 33% vs 25% of patients. Treatment-related death was reported in two patients in the induction group (from heart failure and arrhythmia) and in one patient in the control group (from meningitis).
The investigators concluded: “The targeted-therapy induction regimen did not improve progression-free survival compared with first-line treatment with immune checkpoint inhibitors in unselected patients with advanced melanoma with BRAF V600E or BRAF V600K mutations.”
Caroline Robert, MD, PhD, of the Department of Cancer Medicine, Gustave Roussy Cancer Campus, University of Paris-Saclay, Villejuif, France, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb and Pierre Fabre. For full disclosures of all study authors, visit The Lancet Oncology.
