Antibody drug conjugates: Design implications for clinicians.

OBJECTIVE: There are currently 11 antibody-drug conjugates (ADC) that are FDA approved for use in oncologic disease states, with many more in the pipeline. The authors aim to review the pharmacokinetic profiles of the components of ADCs to engage pharmacist practitioners in practical considerations in the care of patients. This article provides an overview on the use of ADCs in the setting of organ dysfunction, drug-drug interactions, and management of on- and off-target adverse effects. DATA SOURCES: A systematic search of the literature on ADCs through September 2023 was conducted. Clinical trials as well as articles on ADC design and functional components, adverse effects, and pharmacokinetics were reviewed. Reviewed literature included prescribing information as well as tertiary sources and primary literature. DATA SUMMARY: A total of 11 ADCs were reviewed for the purpose of this article. A description of the mechanism of action and structure of ADCs is outlined, and a table containing description of each currently FDA-approved ADC is included. Various mechanisms of ADC toxicity are reviewed, including how ADC structure may be implicated. CONCLUSION: It is imperative that pharmacist clinicians understand the design and function of each component of an ADC to continue to assess new approvals for use in oncology patients. Understanding the design of the ADC can help a pharmacy practitioner compare and contrast adverse effect profiles to support their multidisciplinary teams and to engage patients in education and management of their care.

Incidence of port site complications in relation to timing of bevacizumab infusion.

INTRODUCTION: Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor, with a serious complication of wound healing complications. The package insert currently does not have recommendations on the management of bevacizumab administration around minor procedures, including port placements. Currently, there are only two trials that have examined the optimal timing of bevacizumab after port placement. METHODS: This is a single-center retrospective trial aiming to evaluate the rate of wound dehiscence and other port site complications depending on the time between port placement and bevacizumab infusion. Eligible patients who have had at least one port place and have received bevacizumab for an oncologic indication were identified in a study period of 1/1/2016-3/31/2021. The primary outcome of this study was the incidence of wound dehiscence in relation to the timing of bevacizumab infusion. RESULTS: A total of 243 patients met the inclusion criteria, and 116 port placements had a port site complication. For wound dehiscence, 6% was observed 0 days from port placement, 10% was observed 1 day from port placement, 0% was observed 2 days from port placement, 0% was observed 3-7 days from port placement, 3% was observed 8-14 days from port placement, and 3% was observed 15-30 days from port placement. CONCLUSIONS: The results of this study show an inverse relationship between the risk of wound dehiscence and port site complication and the timing of bevacizumab infusion to port placement, with an increase in absolute risk of wound dehiscence when bevacizumab is given within 2 days of port placement.

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.1 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.

Practical considerations for the use of direct oral anticoagulants in oncology patients.

Oncology patients are at a high risk of experiencing venous thromboembolism. Historically, venous thromboembolisms in cancer patients have been managed with low-molecular-weight heparin on the basis of the CLOT trial published in 2003. However, recent prospective data provide evidence for safe and effective direct oral anticoagulant use in this population. The purpose of this review article is to evaluate the current body of literature surrounding direct oral anticoagulant use in the oncology population and to highlight key practical considerations when prescribing these agents for patients with cancer.