Pyrexia in dabrafenib-treated melanoma patients is not associated with common genetic variation or HLA polymorphisms.

AIM: Pyrexia is a common adverse event (AE) on dabrafenib treatment (monotherapy or combination with trametinib). Since germline SNPs and HLA alleles are implicated in drug-induced AEs, this study investigated their association with pyrexia. PATIENTS & METHODS: 1006 melanoma subjects from five dabrafenib-trametinib clinical studies underwent genotyping for genome-wide SNPs, which enabled imputation of 150 HLA alleles. SNP/HLA allele frequencies were compared between pyrexia cases (n = 218) and controls (n = 361) out of the 1006 subjects by meta-analysis. RESULTS: This analysis had adequate power to detect association of common SNPs or HLA alleles with moderate to large effects on pyrexia (odds ratio >6), but no significant association was found. CONCLUSION: The study suggests that common genetic variation or HLA polymorphisms do not contribute substantially to dabrafenib-induced pyrexia.