A Serum Protein Classifier Identifying Patients with Advanced Non-Small Cell Lung Cancer Who Derive Clinical Benefit from Treatment with Immune Checkpoint Inhibitors.
Clin Cancer Res
; 26(19): 5188-5197, 2020 10 01.
Article
en En
| MEDLINE
| ID: mdl-32631957
ABSTRACT
PURPOSE:
Pretreatment selection of patients with non-small cell lung cancer (NSCLC) who would derive clinical benefit from treatment with immune checkpoint inhibitors (CPIs) would fulfill an unmet clinical need by reducing unnecessary toxicities from treatment and result in substantial health care savings. EXPERIMENTALDESIGN:
In a retrospective study, mass spectrometry (MS)-based proteomic analysis was performed on pretreatment sera derived from patients with advanced NSCLC treated with nivolumab as part of routine clinical care (n = 289). Machine learning combined spectral and clinical data to stratify patients into three groups with good ("sensitive"), intermediate, and poor ("resistant") outcomes following treatment in the second-line setting. The test was applied to three independent patient cohorts and its biology was investigated using protein set enrichment analyses (PSEA).RESULTS:
A signature consisting of 274 MS features derived from a development set of 116 patients was associated with progression-free survival (PFS) and overall survival (OS) across two validation cohorts (N = 98 and N = 75). In pooled analysis, significantly better OS was demonstrated for "sensitive" relative to "not sensitive" patients treated with nivolumab; HR, 0.58 (95% confidence interval, 0.38-0-87; P = 0.009). There was no significant association with clinical factors including PD-L1 expression, available from 133 of 289 patients. The test demonstrated no significant association with PFS or OS in a historical cohort (n = 68) of second-line NSCLC patients treated with docetaxel. PSEA revealed proteomic classification to be significantly associated with complement and wound-healing cascades.CONCLUSIONS:
This serum-derived protein signature successfully stratified outcomes in cohorts of patients with advanced NSCLC treated with second-line PD-1 CPIs and deserves further prospective study.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Sanguíneas
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Carcinoma de Pulmón de Células no Pequeñas
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Antígeno B7-H1
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Inhibidores de Puntos de Control Inmunológico
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Países Bajos