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 |
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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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