Rash in lapatinib-treated patients is not associated with human leukocyte antigen polymorphisms.
Rash is a common side effect of lapatinib treatment. Since human leukocyte antigen (HLA) alleles have been implicated in multiple drug-induced cutaneous reactions, this study investigated the association of HLA alleles with lapatinib-induced rash. 1191 participants from a large lapatinib monotherapy trial underwent HLA genotyping, and allele carriage frequencies between rash cases and controls were compared. This analysis had adequate power to detect an association of common HLA alleles with rash, similar to those reported previously. No HLA alleles were significantly associated with lapatinib-induced rash, including the previously identified lapatinib hepatotoxicity biomarker HLA-DRB1*07:01 (p = 0.87). The present study is consistent with the view that lapatinib-induced rash is not the consequence of HLA-restricted, immune-mediated mechanisms.
PAREXEL International, Research Triangle Park, NC, USA (previously employed by GlaxoSmithKline; work performed on this publication done while employed by GlaxoSmithKline).
Laura R
LR
Parham
PAREXEL International, Research Triangle Park, NC, USA (previously employed by GlaxoSmithKline; work performed on this publication done while employed by GlaxoSmithKline).
Linda P
LP
Briley
PAREXEL International, Research Triangle Park, NC, USA (previously employed by GlaxoSmithKline; work performed on this publication done while employed by GlaxoSmithKline).
Karen S
KS
King
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA (previously employed by GlaxoSmithKline; work performed on this publication done while employed by GlaxoSmithKline).
Julie
J
Byrne
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA (previously employed by GlaxoSmithKline; work performed on this publication done while employed by GlaxoSmithKline).
Erica
E
Rappold
Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Paul E
PE
Goss
GlaxoSmithKline Research & Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
Colin F
CF
Spraggs
D000483:Alleles; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004247:DNA / Q000235:genetics; D003875:Drug Eruptions / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D000077341:Lapatinib; D011110:Polymorphism, Genetic / Q000235:genetics; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D006680:HLA Antigens; D011799:Quinazolines; D000077341:Lapatinib; D004247:DNA
HLA polymorphisms; lapatinib; rash