The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta-analysis

Cancer. 2019 Nov 1;125(21):3776-3789. doi: 10.1002/cncr.32375. Epub 2019 Jul 9.

Abstract

Background: Targeted therapies (TT), combination immunotherapy (CMI), and monoimmunotherapy (MI) in combination with radiotherapy (CRI) or not are commonly used in patients with melanoma brain metastases, but studies that directly compare these strategies are lacking. The current meta-analysis aimed to better elucidate their activity and efficacy.

Methods: A systematic search of MEDLINE, Embase, and conference proceedings up to January 2019 was performed to identify trials investigating combination TT, monotargeted TT (mono TT), MI, CMI, and CRI in melanoma brain metastases. The outcomes considered were progression-free survival (PFS), overall survival (OS), and the objective response rate (ORR) as evaluated at both intracranial and extracranial sites. Random effects models were used to compare the different therapeutic strategies.

Results: A total of 15 trials were included that provided 1132 patients for analyses. CMI demonstrated a statistically significant better OS compared with MI (P = .03, P = .05, and P = .03, respectively, at 6 months, 18 months, and 24 months) and combination TT (P = .04 and P = .03, respectively, at 18 months and 24 months). CMI demonstrated a statistically significant better PFS compared with combination TT (P < .001 at 12 months and 18 months), MI (P = .02, P < .02, and P = .05, respectively, at 6 months, 12 months, and 18 months), and mono TT (P < .001 at 6 months, 12 months, and 18 months). The intracranial objective response rate was higher with CMI compared with mono TT (P < .001) and MI (P < .001), whereas there was no difference between CMI and combination TT.

Conclusions: The results of the current meta-analysis suggested that CMI increases long-term PFS and OS compared with MI and combination TT. Combination TT and CMI are associated with a similar intracranial response rate. The role of systemic therapy in combination with radiotherapy remains to be better elucidated.

Keywords: combination immunotherapy; melanoma brain metastases; overall survival (OS); progression-free survival (PFS); targeted therapy.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Brain Neoplasms / metabolism
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy*
  • Combined Modality Therapy / methods
  • Humans
  • Immunotherapy / methods*
  • Kaplan-Meier Estimate
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma / therapy*
  • Molecular Targeted Therapy / methods*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Radiotherapy / methods
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf