Survival of melanoma patients treated with targeted therapy and immunotherapy after systematic upfront control of brain metastases by radiosurgery

Eur J Cancer. 2017 Oct:84:44-54. doi: 10.1016/j.ejca.2017.07.017. Epub 2017 Aug 4.

Abstract

Background: Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented.

Patients and methods: Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice. Survival after 1st GK (OSGK1) according to prognostic factors and treatment.

Results: Among 179 consecutive pts treated by GK, 109 received IT and/or TT after the 1st GK. Median OSGK1 was 10.95 months and 1- and 2-year survival rates were 49.5% and 27.4%, respectively, versus a median overall survival (OS) of 2.29 months (p < .001) in those who did not receive IT or TT. In pts who initially had a single BM, median OS and 1- and 2-year survival rates were 14.46 months, 66.7% and 43.4%, respectively; in pts with 2-3 BMs: 8.85 months, 46.4% and 31%, respectively; in pts with >3 BMs: 7.25 months, 37.2% and 11.9%, respectively. Multivariate analysis for OSGK1 confirmed that IT and TT were significantly and highly protective. Best OSGK1 was observed in BRAF-wild-type pts receiving anti-PD1 or in BRAF-mutated pts receiving BRAF-inhibitors and anti-PD1 (12.26 and 14.82 months, respectively).

Conclusion: In real-life MM pts with BMs, a strategy aiming at controlling BM with GK together with TT and/or TT seems to achieve unprecedented survival rates.

Keywords: Brain metastasis; Check-point inhibitors; Gamma-Knife radiosurgery; Melanoma; Targeted therapies.

Publication types

  • Comparative Study

MeSH terms

  • Antibodies / adverse effects
  • Antibodies / therapeutic use*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Kaplan-Meier Estimate
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • MAP Kinase Kinase Kinases / metabolism
  • Male
  • Melanoma / enzymology
  • Melanoma / mortality
  • Melanoma / secondary
  • Melanoma / therapy*
  • Middle Aged
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods*
  • Multivariate Analysis
  • Mutation
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Radiosurgery / adverse effects
  • Radiosurgery / methods*
  • Retrospective Studies
  • Risk Factors
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies
  • Antineoplastic Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MAP Kinase Kinase Kinases