Patterns of disease control and survival in patients with melanoma brain metastases undergoing immune-checkpoint blockade.
OBJECTIVES
Immune-checkpoint blockers (ICBs) significantly prolong overall survival (OS) in patients with advanced melanoma. Limited data are available on the efficacy and clinical benefit in patients with melanoma brain metastases (MBMs). The aim of this study was to determine whether ICB is active in an unselected cohort treated of patients with known brain metastases and if disease control correlates with the survival.


METHODS
A total of 385 patients with metastatic malignant melanoma treated with ICB as monotherapy between 2005 and 2017 in two tertiary referral centres were included. Patient records were searched for the development of brain metastases. Demographic and clinical data of all patients were collected retrospectively.


RESULTS
We identified 177 patients with MBM who received ICBs (ipilimumab, nivolumab, pembrolizumab). Patients with and without brain metastases received similar ICB regimens. Prognosis was inferior in patients with brain metastases; patients with >1 brain metastasis showed even poorer survival. For extracranial (ec) metastases, disease control was associated with improved survival. However, when comparing patients with intracranial (ic) disease control during immunotherapy to patients with ic disease progression, no difference in OS could be observed.


CONCLUSIONS
In our study, ec disease control was the dominant predictive factor for OS in both patients with or without melanoma brain metastases. These data indicate that clinical trials in melanoma patients with brain metastases should address end-points such as symptom control, quality of life or OS in addition to ic response rates.
['Milsch|Laura|L|', 'Gesierich|Anja|A|', 'Kreft|Sophia|S|', 'Livingstone|Elisabeth|E|', 'Zimmer|Lisa|L|', 'Goebeler|Matthias|M|', 'Schadendorf|Dirk|D|', 'Schilling|Bastian|B|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000074322:Antineoplastic Agents, Immunological D001921:Brain D001932:Brain Neoplasms D061025:Costimulatory and Inhibitory T-Cell Receptors D018450:Disease Progression D018572:Disease-Free Survival D005260:Female D006801:Humans D007167:Immunotherapy D008297:Male D008545:Melanoma D008875:Middle Aged D011379:Prognosis D011788:Quality of Life D012189:Retrospective Studies D012867:Skin D012878:Skin Neoplasms D016019:Survival Analysis D055815:Young Adult
Melanoma Brain metastases Immune-checkpoint blockade