Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients.
Br J Cancer
; 118(10): 1296-1301, 2018 05.
Article
en En
| MEDLINE
| ID: mdl-29695768
ABSTRACT
BACKGROUND:
Treatment with PD-1 inhibitors can be hampered by severe auto-immune-related toxicities. Our objective was to identify single-nucleotide polymorphisms (SNPs) in genes previously associated with auto-immunity, which are associated with toxicities in nivolumab-treated NSCLC patients. This was in order to identify patients prone to develop severe toxicities and to gain more insight into the underlying pathobiology.METHODS:
We analysed 322 nivolumab-treated patients and assessed the association with toxicities for seven SNPs in four genes, which are considered contributors to PD-1-directed T-cell responses, i.e., PDCD1, PTPN11, ZAP70 and IFNG. Every SNP was tested for its association with toxicity endpoints. Significant associations were tested in a validation cohort.RESULTS:
A multivariable analysis in the exploration cohort showed that homozygous variant patients for PDCD1 804C>T (rs2227981) had decreased odds for any grade treatment-related toxicities (n = 96; OR 0.4; 95% CI 0.2-1.0; p = 0.039). However, this result could not be validated (n = 85; OR 0.9; 95% CI 0.4-1.9; p = NS).CONCLUSIONS:
Our results show that it is unlikely that the investigated SNPs have a clinical implication in predicting toxicity. A finding, even though negative, that is considered timely and instructive towards further research in biomarker development for checkpoint inhibitor treatments.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
/
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
/
Receptor de Muerte Celular Programada 1
/
Nivolumab
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Br J Cancer
Año:
2018
Tipo del documento:
Article
País de afiliación:
Países Bajos