The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study.

Details

Serval ID
serval:BIB_18BD1C202E95
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study.
Journal
Journal of neuro-oncology
Author(s)
Martins F., Schiappacasse L., Levivier M., Tuleasca C., Cuendet M.A., Aedo-Lopez V., Gautron Moura B., Homicsko K., Bettini A., Berthod G., Gérard C.L., Wicky A., Bourhis J., Michielin O.
ISSN
1573-7373 (Electronic)
ISSN-L
0167-594X
Publication state
Published
Issued date
01/2020
Peer-reviewed
Oui
Volume
146
Number
1
Pages
181-193
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Evidence pointing to a synergistic effect of stereotactic radiosurgery (SRS) with concurrent immunotherapy or targeted therapy in patients with melanoma brain metastases (BM) is increasing. We aimed to analyze the effect on overall survival (OS) of immune checkpoint inhibitors (ICI) or BRAF/MEK inhibitors initiated during the 9 weeks before or after SRS. We also evaluated the prognostic value of patients' and disease characteristics as predictors of OS in patients treated with SRS.
We identified patients with BM from cutaneous or unknown primary origin melanoma treated with SRS between 2011 and 2018.
We included 84 patients. The median OS was 12 months (95% CI 9-20 months). The median follow-up was 30 months (95% CI 28-49). Twenty-eight patients with newly diagnosed BM initiated anti-PD-1 +/-CTLA-4 therapy (n = 18), ipilimumab monotherapy (n = 10) or BRAF+/- MEK inhibitors (n = 11), during the 9 weeks before or after SRS. Patients who received anti-PD-1 +/-CTLA-4 mAb showed an improved survival in comparison to ipilimumab monotherapy (OS 24 vs. 7.5 months; HR 0.32, 95% 0.12-0.83, p = 0.02) and BRAF +/-MEK inhibitors (OS 24 vs. 7 months, respectively; HR 0.11, 95% 0.04-0.34, p = 0.0001). This benefit remained significant when compared to the subgroup of patients treated with dual BRAF/MEK inhibition (BMi) (n = 5). In a multivariate Cox regression analysis an age > 65, synchronous BM, > 2 metastatic sites, > 4 BM, and an ECOG > 1 were correlated with poorer prognosis. A treatment with anti-PD-1+/-CTLA-4 mAbs within 9 weeks of SRS was associated with better outcomes. The presence of serum lactate dehydrogenase (LDH) levels ≥ 2xULN at BM diagnosis was associated with lower OS (HR 1.60, 95% CI 1.03-2.50; p = 0.04).
The concurrent administration of anti-PD-1+/-CTLA-4 mAbs with SRS was associated with improved survival in melanoma patients with newly diagnosed BM. In addition to CNS tumor burden, the extension of systemic disease retains its prognostic value in patients treated with SRS. Elevated serum LDH levels are predictors of poor outcome in these patients.
Keywords
Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological/therapeutic use, Brain Neoplasms/immunology, Brain Neoplasms/metabolism, Brain Neoplasms/pathology, Brain Neoplasms/therapy, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Immunotherapy/mortality, Ipilimumab/therapeutic use, Male, Melanoma/immunology, Melanoma/metabolism, Melanoma/pathology, Melanoma/therapy, Middle Aged, Molecular Targeted Therapy/mortality, Prognosis, Protein Kinase Inhibitors/therapeutic use, Radiosurgery/mortality, Retrospective Studies, Survival Rate, BRAF, CTLA-4, CyberKnife, Gamma knife, Immune-checkpoint inhibitors, Immunotherapy, MEK, PD-1, PD-L1, Stereotactic radiation surgery
Pubmed
Web of science
Create date
20/12/2019 12:27
Last modification date
18/06/2020 6:21
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