How would you manage tucatinib-associated grade 2 indirect hyperbilirubinemia in a patient with metastatic HER2-positive breast cancer involving the CNS receiving trastuzumab + capecitabine + tucatinib?

Could she have a UGT1A1 mutation? I have been doing some NGS for hereditary hemolytic anemias and have found asymptomatic Gilbert’s patients with UGT1A1. Tucatinib also has a decrease in UGT1A1 listed in pharmacokinetics so it could lead to a totally harmless indirect hyperbilirubinemia. Checking mi...

Unfortunately, both capecitabine and tucatinib can cause unconjugated hyperbilirubinemia without transaminitis. In this case, it looks like it is clearly related to tucatinib. In this heavily pretreated young patient with CNS involvement, if the patient is asymptomatic from the hyperbilirubinemia (l...