A real-world study of adjuvant anti-PD -1 immunotherapy on stage III melanoma with BRAF, NRAS, and KIT mutations

Cancer Med. 2023 Aug;12(15):15945-15954. doi: 10.1002/cam4.6234. Epub 2023 Jul 5.


Background: Melanoma frequently harbors BRAF, NRAS, or KIT mutations which influence both tumor development and treatment strategies. For example, it is still controversial whether adjuvant anti-PD-1 monotherapy or BRAF/MEK inhibitors may better improve the survival for resected BRAF-mutant melanoma. Furthermore, outcomes for melanoma with NRAS and KIT mutation receiving adjuvant immunotherapy remain unclear.

Methods: One hundred seventy-four stage III melanoma patients who underwent radical surgery in Fudan University Shanghai Cancer Center (FUSCC) during January 2017 to December 2021 were included in this real-world study. Patients were followed up until death or May 30th, 2022. Pearson's chi-squared test or Fisher's exact test was performed for univariable analysis of the different category groups. Log-rank analysis was used to identify the prognostic factors for disease-free survival (DFS).

Results: There were 41 (23.6%) patients with BRAF mutation, 31 (17.8%) with NRAS mutation, 17 (9.8%) with KIT mutation, and 85 (48.9%) wild-type patients without either genomic alteration of those three genes. Most ( n = 118, 67.8%) of them were acral melanoma, while 45 (25.9%) were cutaneous subtype, and 11 were (6.3%) primary unknown. Among them, 115 (66.1%) patients received pembrolizumab or toripalimab monotherapy as adjuvant therapy; 22 (12.6%) patients received high-dose interferon (IFN), and 37 (21.3%) patients were just for observation. There was no statistical difference in clinicopathologic factors between anti-PD-1 group and IFN/OBS group. Of all the enrolled patients, anti-PD-1 group had a better DFS than IFN/OBS group ( p = 0.039). In anti-PD-1 group, patients with BRAF or NRAS mutations had poorer DFS than wild-type group. No survival difference was found among patients harboring different gene mutations in IFN/OBS group. In wild-type patients, anti-PD-1 group had a better DFS than IFN/OBS group ( p = 0.003), while no survival benefits were found for patients with BRAF, NRAS, or KIT mutations.

Conclusion: Although anti-PD-1 adjuvant therapy provides a better DFS in the general population and in wild-type patients, patients with BRAF, KIT or, especially, NRAS mutation may not benefit further from immunotherapy than conventional IFN treatment or observation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • China
  • GTP Phosphohydrolases / genetics
  • Humans
  • Immunotherapy
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Membrane Proteins / genetics
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / genetics


  • Adjuvants, Immunologic
  • BRAF protein, human
  • GTP Phosphohydrolases
  • Membrane Proteins
  • NRAS protein, human
  • Proto-Oncogene Proteins B-raf

Supplementary concepts

  • Melanoma, Cutaneous Malignant