BRAF/MEK Inhibition as a Bridge to Immunotherapy for Symptomatic BRAF V600 Melanoma Brain Metastases: A Case Series

J Natl Compr Canc Netw. 2023 Aug 29;21(10):991-999. doi: 10.6004/jnccn.2023.7032.

Abstract

Targeted and immune therapies have changed the paradigm of treatment for patients with metastatic melanoma. Treatment of patients with symptomatic melanoma brain metastases, however, is complicated by the frequent use of immune suppression for the management of vasogenic edema and the urgency in addressing disease burden. Use of BRAF/MEK inhibitors in patients with a corresponding BRAF V600 mutation often results in rapid response but is hindered by high rates of disease relapse and progression. Immunotherapy has higher durability of response, but the rate of response is slower and responses can be significantly diminished for patients on concurrent steroid therapy. Considering this gap in evidence-based guidance for optimal adjuvant therapy sequence in immunosuppressed patients with BRAF V600-mutant melanoma brain metastases, we report on 4 cases utilizing BRAF/MEK inhibitors as a bridging therapy for brain metastases management before initiation of immune checkpoint inhibitor therapy. Future prospective studies will be required to determine the optimal treatment sequencing for patients in this population with high unmet medical need.

Keywords: BRAF/MEK Inhibitor; bridging therapy; immunotherapy; metastatic melanoma; targeted therapy.

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / therapy
  • Humans
  • Immunotherapy
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mutation
  • Neoplasm Recurrence, Local
  • Prospective Studies
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms* / therapy

Substances

  • Proto-Oncogene Proteins B-raf
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase Kinases
  • BRAF protein, human