Lenvatinib plus pembrolizumab did not show additional clinical benefit over pembrolizumab alone in advanced melanoma. Although progression-free survival was initially improved, overall survival was not. Pembrolizumab remains the standard of care in this setting.
Study
Randomized, double-blind, placebo-controlled phase III study [LEAP-003] |
Unresectable stage III or IV melanoma |
Lenvatinib+Pembrolizumab (n=334) vs Placebo+Pembrolizumab (n=340)
|
Efficacy
PFS: 8.4 mos vs 4.0 mos (HR 0.72 [0.59-0.88]) |
mPFS at final: 10.1 mos vs 4.2 mos (HR 0.83 [0.69-1.00]) |
mOS: 25.8 mos vs 39.5 mos (HR 1.20 [0.97-1.48]) |
ORR: 43.4% vs 35.6%
|
Safety
Grade >=3 AE: 58.7% vs 29.0% |
Discontinuation due to AEs: 25.9% vs 15.4% |
Treatment-related deaths: 0.6% vs 0.9%
|
Ann Oncol. Published online 2025
Arance A, Berciano-Guerrero MA, Guo J New Reference: Lenvatinib + Pembrolizumab for Melanoma
http://doi.org/10.1016/j.annonc.2025.08.008
Reviewed by Ulas D. Bayraktar, MD on Oct 20, 2025