Case report of sacituzumab govitecan-hziy-induced neutropenia in a patient with metastatic triple-negative breast cancer and a uridine diphosphate glucuronosyltransferase family 1 member A1 poor metabolizer genotype.

Introduction: Sacituzumab govitecan-hziy, approved in 2020 for treatment of metastatic triple-negative breast cancer, provides a new option for a population with a historically poor prognosis with standard chemotherapy. Uridine diphosphate glucuronosyltransferase family 1 member A1 poor metabolizers are at increased risk for profound neutropenia. This case discusses clinical implications of the uridine diphosphate glucuronosyltransferase family 1 member A1*28/*28 genotype in patients receiving sacituzumab govitecan-hziy.

Case Report: A 38-year-old otherwise healthy pre-menopausal female of South Asian descent was diagnosed with non-metastatic, hormone receptor-positive, and human epidermal growth factor receptor 2-negative breast cancer. This was treated with neoadjuvant chemotherapy and multiple lines of subsequent therapies. Upon finding bone metastasis, an additional six lines of therapy ensued. In total, 3.5 years post-diagnosis, sacituzumab govitecan-hziy was started for disease transformation to triple-negative status.

Management And Outcome: Sacituzumab govitecan-hziy was initiated at the Food and Drug Administration-approved 10 mg/kg/dose on days 1 and 8 of a 21-day cycle. Grade 4 neutropenia occurred after one dose. Pharmacogenomics testing identified the patient as a uridine diphosphate glucuronosyltransferase family 1 member A1*28 homozygous expressor. Sacituzumab govitecan-hziy was dose-reduced, and granulocyte colony-stimulating factor was administered due to the severity of neutropenia. The patient continued on sacituzumab govitecan-hziy until disease progression.

Discussion: Sacituzumab govitecan-hziy's propensity to cause neutropenia is multifactorial. Although incidence of all-grade neutropenia from sacituzumab govitecan-hziy is elevated for uridine diphosphate glucuronosyltransferase family 1 member A1*28 homozygous expressors, this does not translate to increased risk for febrile neutropenia. Detailed guidance is lacking regarding empiric dose adjustments or prophylactic granulocyte colony-stimulating factor for these patients. Currently, pre-sacituzumab govitecan-hziy pharmacogenomics testing to identify uridine diphosphate glucuronosyltransferase family 1 member A1 poor metabolizers is not recommended, and the cost-effectiveness of this approach is unclear.