Real-life data for first-line combination immune-checkpoint inhibition and targeted therapy in patients with melanoma brain metastases.

Details

Serval ID
serval:BIB_A82FBE1EAA00
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Real-life data for first-line combination immune-checkpoint inhibition and targeted therapy in patients with melanoma brain metastases.
Journal
European journal of cancer
Author(s)
Hilbers M.L., Dimitriou F., Lau P., Bhave P., McArthur G.A., Zimmer L., Kudura K., Gérard C.L., Levesque M.P., Michielin O., Dummer R., Cheng P.F., Mangana J.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
25/08/2021
Peer-reviewed
Oui
Volume
156
Pages
149-163
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Melanoma brain metastases (MBM) have a poor prognosis. Systemic treatments that have improved outcomes in advanced melanoma have been shown to have an intracranial (IC) effect. We studied the efficacy and outcomes of combined immune checkpoint inhibitor ipilimumab/nivolumab (Combi-ICI) or targeted therapy (Combi-TT) as first-line treatment in MBM.
MBM patients treated with Combi-ICI or Combi-TT within 3 months after MBM diagnosis. Endpoints were progression-free survival (PFS) and overall survival (OS).
53 patients received Combi-ICI, 32% had symptomatic MBM and 33.9% elevated LDH. 71.7% required local treatment. The disease control rate was 60.3%. IC response rate (RR) was 43.8% at 3-months with durable responses at 6- (46.5%) and 12-months (53.1%). Extracranial (EC) RR was 44.7% at 3-months and 50% at 12-months. Median PFS was 9.6 months (95% CI 3.6-NR) and median overall survival (mOS) 44.8 months (95% CI; 26.2-NR). 63 patients received Combi-TT, 55.6% of patients had symptomatic MBM, 57.2% of patients had elevated LDH and 68.3% of patients required local treatment. The disease control rate was 60.4%. ICRR was 50% at 3-months, but dropped at 6-months (20.9%). ECRR was 69.2% at 3-months and 17.6% at 12-months. Median PFS was 5.8 months (95% CI 4.2-7.6) and mOS 14.2 months (95% CI 8.99-26.8). In BRAFV600 patients, 26.7% of patients received Combi-ICI and 73.3% Combi-TT with OS (p = 0.0053) and mPFS (p = 0.03) in favour to Combi-ICI.
Combi-ICI showed prolonged mOS with sustainable IC and EC responses. Despite the initially increased efficacy, Combi-TT responses at 12 months were low. Combi-ICI appeared superior to Combi-TT for OS and PFS in BRAFV600 patients. Other clinical factors are determinants for first-line treatment choice.
Keywords
Immunotherapy, Melanoma brain metastasis, Stereotactic radiosurgery, Targeted therapy
Pubmed
Open Access
Yes
Create date
15/09/2021 10:40
Last modification date
12/10/2021 6:40
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