Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies

BMC Cancer. 2018 Apr 27;18(1):490. doi: 10.1186/s12885-018-4374-x.

Abstract

Background: Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs.

Methods: We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015.

Results: The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis.

Conclusions: These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

Keywords: BRAF; Brain; Checkpoint inhibitors; Melanoma; Metastasis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / secondary*
  • CTLA-4 Antigen / antagonists & inhibitors
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / pathology*
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf