Topics:
Breast Cancer • Medical Oncology • NCI-CCC Tumor Board Question • Yale • Her2+ • NCI-CCC Breast Tumor Board Question • Breast Cancer, Metastatic
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?
Patient is young. Bilirubin normalizes when tucatinib is held, but again increases to grade 2 when it is restarted. Evaluation for hemolysis was negative. Direct bilirubin normal and no obvious liver toxicity.
How might your management change if a patient already progressed on THP, T-DM1 and T-Dxd?
Answer from: Medical Oncologist at Community Practice
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. Check...
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Answer from: Medical Oncologist at Academic Institution
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...