Proteomic test for anti-PD-1 checkpoint blockade treatment of metastatic melanoma with and without BRAF mutations

Autor: Antonio M. Grimaldi, Joanna Roder, Paolo A. Ascierto, Senait Asmellash, Julia Grigorieva, Heinrich Roder, Gabriele Madonna, Ester Simeone, Carlos R. Oliveira, Krista Meyer, Mariaelena Capone, Domenico Mallardo
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Oncology
Male
Proteomics
Cancer Research
medicine.medical_treatment
Pembrolizumab
B7-H1 Antigen
Targeted therapy
0302 clinical medicine
Antineoplastic Agents
Immunological
Immunology and Allergy
Neoplasm Metastasis
Melanoma
Aged
80 and over
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Anti-PD-1
Nivolumab
Treatment Outcome
030220 oncology & carcinogenesis
Molecular Medicine
Biomarker (medicine)
Female
Immunotherapy
Adult
Proto-Oncogene Proteins B-raf
medicine.medical_specialty
Immunology
Short Report
BRAF mutations
Antibodies
Monoclonal
Humanized
lcsh:RC254-282
03 medical and health sciences
Internal medicine
medicine
Biomarkers
Tumor
Humans
neoplasms
Aged
Retrospective Studies
Pharmacology
business.industry
medicine.disease
Survival Analysis
Immune checkpoint
Blockade
030104 developmental biology
Mutation
Proteomic test
business
Zdroj: Journal for Immunotherapy of Cancer
Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-8 (2019)
ISSN: 2051-1426
Popis: The therapeutic landscape in metastatic melanoma has changed dramatically in the last decade, with the success of immune checkpoint inhibitors resulting in durable responses for a large number of patients. For patients with BRAF mutations, combinations of BRAF and MEK inhibitors demonstrated response rates and benefit comparable to those from immune checkpoint inhibitors, providing the rationale for sequential treatment with targeted and immunotherapies and raising the question of optimal treatment sequencing. Biomarkers for the selection of anti-PD-1 therapy in BRAF wild type (BRAF WT) and in BRAF mutated (BRAF MUT) patients help development of alternative treatments for patients unlikely to benefit, and might lead to better understanding of the interaction of checkpoint inhibition and targeted therapy. In this paper we evaluate the performance of a previously developed serum proteomic test, BDX008, in metastatic melanoma patients treated with anti-PD-1 agents and investigate the role of BRAF mutation status. BDX008, a pre-treatment proteomic test associated with acute phase reactants, wound healing and complement activation, stratifies patients into two groups, BDX008+ and BDX008-, with better and worse outcomes on immunotherapy. Serum samples were available from 71 patients treated with anti-PD1 inhibitors; 25 patients had BRAF mutations, 39 were wild type. Overall, BDX008+ patients had significantly better overall survival (OS) (HR = 0.50, P = 0.016) and a trend for better progression-free survival (PFS) (HR = 0.61, P = 0.060) than BDX008- patients. BDX008 classification was statistically significant in the analyses adjusted for mutation status, LDH, and line of treatment (P = 0.009 for OS and 0.031 for PFS). BRAF WT BDX008+ patients had markedly long median OS of 32.5 months and 53% landmark 2 years survival, with statistically significantly superior OS as compared to BDX008- patients (HR = 0.41, P = 0.032). The difference between BDX008+ and BDX008- in PFS in BRAF WT patients and in OS and PFS in BRAF MUT patients did not reach statistical significance, though numerically was consistent with overall results. The test demonstrated significant interaction with neutrophil-to-lymphocyte ratio (NLR) (PFS P = 0.041, OS P = 0.004). BDX008 as a biomarker selecting for benefit from immune checkpoint blockade, especially in patients with wild type BRAF and in subgroups with low NLR, warrants further evaluation. Electronic supplementary material The online version of this article (10.1186/s40425-019-0569-1) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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