Pembrolizumab extends recurrence-free survival in high-risk melanoma
Pembrolizumab delivered intravenously every 3 weeks for 1 year extended recurrence-free survival (RFS) in patients with resected stage III melanoma, according to results of the KEYNOTE-054/EORTC 1325-MG* trial.
“We were pleased to see that adjuvant pembrolizumab, given as a flat dose of 200 mg every 3 weeks after surgery for up to a year, which is 18 doses, significantly reduced the risk of recurrence for patients with high-risk stage III melanoma that has been completely resected,” said study lead author Professor Alexander Eggermont, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR 2018).
In this multinational (123 centres in 23 countries), phase III clinical trial, 1,019 adult patients with stage III melanoma who had undergone complete regional lymphadenectomy within 13 weeks prior to treatment initiation were randomized to receive intravenous infusions of pembrolizumab (200 mg; n=514) or placebo (n=505) every 3 weeks for approximately 1 year (18 doses) or until disease recurrence or unacceptable toxicity. Patients were followed-up for a median 15.1 months.
More patients on pembrolizumab remained recurrence-free at 12 months compared with those on placebo (75.4 percent vs 61.0 percent), with a significantly longer RFS (hazard ratio [HR], 0.57, 98.4 percent confidence interval [CI], 0.43–0.74; p<0.001). [AACR 2018, CT001; N Engl J Med 2018;doi:10.1056/NEJMoa1802357]
RFS at 12 months was longer in patients on pembrolizumab compared with placebo regardless of their PD-1 ligand (PD-L1) status (HR, 0.54, 95 percent CI, 0.42–0.69; p<0.001 for the 853 PD-L1-positive patients and HR, 0.47, 95 percent CI, 0.26–0.85; p=0.01 for the 116 PD-L1-negative patients).
Treatment discontinuation due to adverse events (AEs) occurred in 70 and 11 patients on pembrolizumab and placebo, respectively. Treatment-related grade 3–5 AEs were more common among patients on pembrolizumab compared with placebo (14.7 percent vs 3.4 percent), with one death due to myositis in the pembrolizumab group. Though overall incidence was low, grade 3–4 immune-related AEs also occurred more frequently among patients on pembrolizumab than placebo (7.1 percent vs 0.6 percent).
Referring to previous research that demonstrated longer progression-free and overall survival with pembrolizumab in advanced melanoma, [N Engl J Med 2015;372:2521-2532] researchers suggested that findings from this study “provide more evidence that drugs that are effective in advanced melanoma also have effectiveness as adjuvant therapy”.
Patients assigned to placebo who experienced recurrence were permitted to crossover to receive pembrolizumab while those who received pembrolizumab and experienced recurrence could repeat pembrolizumab treatment.
“This crossover design is unique in the world of adjuvant trials in melanoma and will permit us to analyse if adjuvant therapy with pembrolizumab right after surgery is better or not than treating only those who relapse and start treatment at relapse,” said Eggermont.