Association Between Single-nucleotide Polymorphisms and Adverse Events in Nivolumab-treated Non-small Cell Lung Cancer Patients

Overview

Journal Br J Cancer

Specialty Oncology

Date 2018 Apr 27

PMID 29695768

Citations 37

Authors

Sander Bins

Edwin A Basak

Samira El Bouazzaoui

Stijn L W Koolen

E Oomen-de Hoop

Cor H van der Leest

Astrid A M van der Veldt

Stefan Sleijfer

Reno Debets

Ron H N van Schaik

Joachim G J V Aerts

Ron H J Mathijssen

Affiliations

Soon will be listed here.

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.

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