The addition of spartalizumab to dabrafenib and trametinib demonstrated a long-term survival benefit in patients with BRAF V600–mutant metastatic melanoma, according to the final overall survival analysis from the phase III COMBI-I trial published in the Journal of Clinical Oncology.
“[T]he combination of spartalizumab plus dabrafenib and trametinib for the treatment of patients with BRAF V600–mutant metastatic melanoma suggests a trend for survival benefits over targeted therapy alone,” the study authors, including corresponding and lead study author Antoni Ribas, MD, of the University of California Los Angeles, wrote in their published report.
Study Methods
The multicenter phase III COMBI-I trial enrolled adult patients with unresectable or metastatic BRAF V600–mutant melanoma. Patients were randomly assigned to receive spartalizumab plus dabrafenib and trametinib (n = 267) or dabrafenib and trametinib plus placebo (n = 265).
The trial failed to reach its primary endpoint of progression-free survival benefit with the addition of spartalizumab. The median progression-free survival was 16.2 months in the added spartalizumab arm vs 12.0 months in the dabrafenib and trametinib alone arm (hazard ratio [HR] = 0.82; 95% confidence interval [CI] = 0.66–1.03; one-sided P = .042), which was considered nonsignificant.
Patients continued to be followed through the end of the trial with a median follow-up duration of 76.9 months (range = 73.7–83.3 months). “The COMBI-I trial has the longest reported follow-up when compared with other studies that investigated the combination of an immune checkpoint inhibitor with BRAF and MEK inhibitors,” the study authors noted.
Key Findings
In the final overall survival analysis, the median overall survival was 61.5 months (95% CI = 41.6 months to not evaluable) in the spartalizumab arm compared with 41.6 months (95% CI = 30.6–56.9 months) in the arm without spartalizumab (HR = 0.760; 95% CI = 0.598–0.966).
At 60 months, the estimated overall survival rates were 50.1% for patients receiving spartalizumab vs 42.8% for those who instead received placebo.
Safety findings were consistent with the known safety profile for the combination of spartalizumab with dabrafenib and trametinib. The most common treatment-related adverse event was pyrexia in 65.9% of patients in the arm with spartalizumab and in 46.2% of patients in the arm with placebo. Grade 3 or higher treatment-related adverse events were observed in 57.3% of patients in the triplet arm and in 36.7% of patients in the doublet arm.
Post-treatment therapy was required for 46.1% of patients in the spartalizumab arm vs for 50.6% of patients in the arm without spartalizumab. The most common post-treatment therapy was immunotherapy.
DISCLOSURES: The study was supported by Novartis Pharmaceuticals Corporation. For full disclosures of the study authors, visit ascopubs.org.
