Association Of Hyperbilirubinemia In Pazopanib- Or Sunitinib-Treated Patients In Comparz With Ugt1a1 Polymorphisms

4569 Background: A phase III randomized clinical trial (COMPARZ) comparing pazopanib vs sunitinib for treatment of advanced renal cell carcinoma demonstrated similar efficacies but different safety profiles for the two therapies. Elevations in serum total bilirubin have been observed in patients receiving either therapy. UGT1A1 polymorphisms are associated with elevated bilirubin in the general population (Gilbert’s syndrome). This study investigated the association between functional UGT1A1 polymorphisms and on-therapy serum total bilirubin in the COMPARZ study. Methods: Patients homozygous or compound heterozygous for UGT1A1 *28, *37, and *6 alleles were predicted to have reduced UGT1A1 function. Logistic regression adjusted for ancestry principal components was used to compare patients with on-therapy hyperbilirubinemia (≥1.5 × upper limit of normal [ULN]; pazopanib, N = 62; sunitinib, N = 34) against patients exposed to treatment and with maximum on-therapy bilirubin ≤1 × ULN (pazopanib, N = 213; suni...