Survival of patients with melanoma brain metastasis treated with stereotactic radiosurgery and active systemic drug therapies

Eur J Cancer. 2017 Apr:75:169-178. doi: 10.1016/j.ejca.2017.01.007. Epub 2017 Feb 23.

Abstract

Introduction: With new systemic therapies demonstrating activity in melanoma brain metastasis, most of the previously reported stereotactic radiosurgery (SRS) data are superseded. In this study, we report the outcomes (overall survival [OS] and brain control [BC]) and identify factors that associate with such outcomes in the era of modern systemic therapy.

Method: A total of 108 patients treated with SRS from 2010 to 2015 were included. Systemic treatment use within 6 weeks of SRS was noted. OS was defined as time from SRS to death or last follow-up, and BC was defined as absence of any active intracranial disease during follow-up. Univariate and multivariate Cox proportional hazard analyses were performed on clinico-pathological prognostic features associated with OS and BC.

Results: The median age was 64.3 years, and the median follow-up was 8.6 months. Seventy-nine (73.1%) patients received systemic treatment. The median OS were as follows: anti-CTLA4 - 7.5 months (95% CI: 4.4-15.6), anti-PD1 - 20.4 months (95% CI: 8.8 - N/A) and BRAF inhibitor (BRAFi) ± MEK inhibitor (MEKi) - 17.8 months (95% CI: 11.8 - N/A). Median BC was as follows: anti-CTLA4 - 7.5 months (95% CI: 4.0-15.6), anti-PD1 - 12.7 months (95% CI: 5.5 - N/A) and BRAFi ± MEKi - 12.7 months (95% CI: 8.3-18.5). In multivariate analysis, age and type of systemic therapy were strongly associated with OS. Age, Eastern Cooperative Oncology Group performance status, Graded Prognostic Assessment (GPA) score, and presence of symptoms were associated with BC.

Conclusions: Favourable outcomes are seen in patients treated with SRS and with the best survival seen in patients treated with anti-PD1. Known independent prognostic factors for survival such as age and performance status and GPA score remain relevant in this setting.

Keywords: Anti-PD-1 antibody; BRAF inhibitors; Brain metastasis; Immunotherapy; Melanoma; Stereotactic radiosurgery; Targeted therapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / secondary
  • Combined Modality Therapy
  • Female
  • Humans
  • Immunotherapy / methods
  • MAP Kinase Kinase 1 / antagonists & inhibitors
  • Male
  • Melanoma / mortality
  • Melanoma / radiotherapy*
  • Melanoma / secondary
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / mortality
  • Positron-Emission Tomography
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Radiosurgery / methods*
  • Radiosurgery / mortality
  • Skin Neoplasms*
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Young Adult

Substances

  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human