HLA polymorphisms influence the development of skin rash arising from treatment with EGF receptor inhibitors.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
German Red Cross Blood Transfusion Service, Baden-Wuerttemberg-Hessen, Ulm, Germany.
Daniel
D
Fuerst
Sumit
S
Parmar
Christian
C
Schumann
Stefan
S
Rüdiger
Stefan
S
Boeck
Volker
V
Heinemann
Volker
V
Kaechele
Kristina
K
Stiebel
Tanusree
T
Paul
Thomas
T
Seufferlein
Joannis
J
Mytilineos
Julia Carolin
JC
Stingl
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects; D003875:Drug Eruptions / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005076:Exanthema / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D011379:Prognosis
D000970:Antineoplastic Agents; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059811:HLA-DRB1 Chains; D066246:ErbB Receptors