Melanoma brain metastases: is it time to reassess the bias?

Abstract

Melanoma patients with brain metastases are typically excluded from clinical trials due to historically dismal survival (<4 months) and concerns about blood brain barrier drug penetration. The pleural cavity is another location with potential decreased drug penetrance, yet malignant effusion patients are not excluded. Here we discuss whether new technologies for local control of brain metastases have altered survival patterns. We also report our findings from a retrospective chart review of 251 metastatic melanoma patients diagnosed after 2005, and evaluate our findings in the context of eligibility for clinical trials with novel agents. We found that median survival of malignant effusion patients was significantly shorter than brain metastasis patients (two versus eight months, p < 0.0001). Only one pleural effusion patient lived >9 months, whereas 41 (39.4%) brain metastasis patients survived beyond this time. We conclude that with the advent of effective means for providing local control for brain metastases, survival of these patients has improved, and they often succumb to extra-cranial disease. Exclusion of melanoma brain metastasis patients from clinical research programs is no longer justified and alternative investigational approaches, possibly combining local and systemic therapies, are urgently needed for these individuals.

Figure 1

Kaplan-Meier Curves demonstrating the overall survival from time of diagnosis of metastatic pleural effusion or from time of brain metastases, respectively. Patients with pleural effusions had significantly shorter survival than patients with brain metastases (p<0.0001).