As reported in the Journal of Clinical Oncology by Caroline Robert, MD, PhD, and colleagues, the 7-year follow-up of the phase III KEYNOTE-006 trial has shown a continued overall survival benefit with pembrolizumab vs ipilimumab in patients with advanced melanoma.
The primary analysis of the trial supported the December 2015 approval of the expanded indication for pembrolizumab to include first-line treatment of patients with unresectable or metastatic melanoma.
Caroline Robert, MD, PhD
Study Details
In the trial, patients with unresectable stage III or stage IV melanoma were randomly assigned 2:1 to receive either pembrolizumab at 10 mg/kg once every 2 or 3 weeks for up to 2 years (n = 556) or ipilimumab at 3 mg/kg once every 3 weeks for four cycles (n = 278).
Key Findings
At the 5-year analysis, median overall survival was 32.7 months with pembrolizumab vs 15.9 months with ipilimumab, with a 5-year rate of 38.7% vs 31.0%.
At the 7-year analysis (data cutoff in April 2021), median follow-up was 85.3 months (range = 0.03–90.8 months). Median overall survival was 32.7 months (95% confidence interval [CI] = 24.5–41.6 months) in the pembrolizumab group vs 15.9 months (95% CI = 13.3–22.0 months) in the ipilimumab group (hazard ratio [HR] = 0.70, 95% CI = 0.58–0.83); the rate at 7 years was 37.8% vs 25.3%.
Median overall survival was also improved with pembrolizumab among patients with previously untreated disease (HR = 0.67, 95% CI = 0.53–0.84), with a 7-year rate of 41.2% vs 27.6%. Overall survival hazard ratios favored pembrolizumab in subgroups according to BRAF status and prior BRAF/MEK inhibitor treatment (eg, 0.58 for BRAF-mutant with no prior treatment, and 0.72 for BRAF-mutant with prior treatment), elevated lactate dehydrogenase (0.59), large tumor size (0.67), and presence of brain metastasis (0.49).
Median modified progression-free survival (patients without a known event were censored at the date last seen) was 9.4 months in the pembrolizumab group (95% CI = 6.7–11.6 months) vs 3.8 months in the ipilimumab group (95% CI = 2.9–4.3 months); the 7-year rate was 23.8% vs 13.3%. Median modified progression-free survival was also improved with pembrolizumab among patients with previously untreated disease (HR = 0.62, 95% CI = 0.50–0.76), with a 7-year rate of 26.8% vs 15.9%.
Among 103 patients who completed at least 94 weeks of pembrolizumab and had stable disease or better, the 5-year overall survival rate was 92.9%, and the 5-year modified progression-free survival rate was 70.1%.
Among 16 patients in the pembrolizumab group who received second-course pembrolizumab, objective response was observed in 9 (56%), and the 2-year modified progression-free survival was 62.5%.
The investigators concluded: “These findings confirm that pembrolizumab provides long-term survival benefit in advanced melanoma.”
Dr. Robert, of Gustave Roussy, Villejuif, France, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.
