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Updated: Aug 28, 2025

Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
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BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma

Olivier J van Not1,2, Willeke A M Blokx3, Alfons J M van den Eertwegh4

  • 1Scientific Bureau, Dutch Institute for Clinical Auditing, Leiden, the Netherlands.

JCO Precision Oncology
|September 21, 2022
PubMed
Abstract

Insights

BRAF mutations improve outcomes for advanced melanoma patients treated with ipilimumab-nivolumab. This finding suggests BRAF status is key when selecting immune checkpoint inhibitors for melanoma treatment.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Immune checkpoint inhibitors (ICIs) have revolutionized advanced melanoma treatment.
  • The impact of specific gene mutations, such as BRAF and NRAS, on ICI efficacy remains incompletely understood.

Purpose of the Study:

  • To investigate the association between BRAF and NRAS gene mutations and the efficacy of first-line immune checkpoint inhibitors in advanced melanoma.
  • To analyze objective response rate, progression-free survival (PFS), and overall survival (OS) based on mutation status.

Main Methods:

  • A nationwide cohort study included advanced melanoma patients treated with anti-PD-1 or ipilimumab-nivolumab from 2012-2021.
  • Progression-free survival (PFS) and overall survival (OS) were analyzed according to BRAF and NRAS mutational status.
  • Multivariable Cox regression models assessed prognostic factors for PFS and OS.

Main Results:

  • In the ipilimumab-nivolumab cohort, BRAF-mutant melanoma showed significantly longer median PFS (9.9 months) compared to NRAS-mutant (4.8 months) and wild-type (5.3 months).
  • BRAF-mutant melanoma was associated with a lower risk of progression or death in the ipilimumab-nivolumab group.
  • Both ICI regimens demonstrated significantly higher median OS for BRAF-mutant melanoma.

Conclusions:

  • Ipilimumab-nivolumab treatment confers improved PFS and OS in BRAF-mutant advanced melanoma patients compared to those with NRAS-mutant or wild-type melanoma.
  • BRAF mutation status is a critical factor to consider when deciding between monotherapy and dual immune checkpoint inhibition for advanced melanoma.

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