HLA Polymorphisms Influence the Development of Skin Rash Arising from Treatment with EGF Receptor Inhibitors

Abstract

Aim: Development of a skin rash under treatment with EGF receptor (EGFR) inhibitors (EGFRIs) has been linked to a favorable prognosis in some studies, suggesting a possible immunological role for EGFRIs in addition to direct antagonistic downstream effects. The present study aimed to investigate whether particular HLA polymorphisms found in cancer patients treated with EGFRIs are associated with the development of skin rash and overall survival rates. Patients & methods: HLA typing was performed on 105 cancer patients and the development of skin rash was rated during the first 4 weeks of therapy with EGFRIs. Results: A significantly lower incidence of skin rash was found in patients carrying the HLA-A*02:01 or HLA-A*03:01 alleles (hazard ratio: 0.277; 95% CI: 0.121–0.634; p = 0.002 and hazard ratio: 0.292; 95% CI: 0.113–0.752; p = 0.011, respectively); however, no association with worse survival was seen. Conclusion: The chances of developing a skin rash in patients treated with EGFRIs may be lower in patients that carry the HLA-A*02:01 or HLA-A*03:01 alleles, while the antitumor efficacy of EGFRIs does not seem to be significantly impaired in these patients.

Original submitted 20 April 2012; Revision submitted 9 July 2012

KEYWORDS::

• drug hypersensitivity
• EGFR
• HLA
• polymorphism
• skin rash

Financial & competing interests disclosure

This study was financially supported by a research grant from the Wilhelm Sander Foundation (grant No 2008.017.1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was financially supported by a research grant from the Wilhelm Sander Foundation (grant No 2008.017.1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.