First-line pembrolizumab versus dabrafenib/trametinib treatment for BRAF V600-mutant advanced melanoma
Authors
Chang Gon Kim ; Miso Kim ; Jieon Hwang ; Seung Tae Kim ; Minkyu Jung ; Kyoo Hyun Kim ; Kyung Hwan Kim ; Jee Suk Chang ; Woong Sub Koom ; Mi Ryung Roh ; Kee Yang Chung ; Tae Min Kim ; Sang Kyum Kim ; Jeeyun Lee ; Sang Joon Shin
Citation
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, Vol.87(5) : 989-996, 2022-11
Background: Limited data are available to assist the selection between immune checkpoint inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors as first-line treatment for patients with BRAF-mutant advanced malignant melanoma.
Objective: To investigate the outcomes associated with first-line pembrolizumab or dabrafenib/trametinib treatment for advanced melanoma with activating BRAF V600 mutation.
Methods: Data of patients with BRAF V600-mutant melanoma who were treated with first-line pembrolizumab (n = 40) or dabrafenib/trametinib (n = 32) were analyzed. Tumor response, progression-free survival, and overall survival were evaluated. Immune evasion accompanied with emerging resistance to BRAF/mitogen-activated protein kinase kinase inhibitors was assessed.
Results: A longer overall survival was observed after first-line pembrolizumab treatment than after first-line dabrafenib/trametinib treatment (hazard ratio = 2.910, 95% CI: 1.552-5.459), although there were no significant differences in progression-free survival (P = .375) and response rate (P = .123). Emergence of resistance to dabrafenib/trametinib co-occurred with immune evasion, enabling melanoma cells to escape recognition and killing by Melan-A-specific CD8+ T cells.
Limitations: Analysis was conducted in a retrospective manner.
Conclusion: Pembrolizumab may be recommended over BRAF/mitogen-activated protein kinase kinase inhibitors as the first-line treatment in patients with advanced BRAF V600-mutant melanoma.