Risk Minimization of Antibody-Drug Conjugates in Oncology: A Review.

Antibody-drug conjugates (ADCs) are new treatment options for certain cancers, especially those in advanced states with limited treatment options. Their unique design provides targeted therapy with toxins that otherwise would not be available, but they manifest toxicities that require risk minimization interventions to optimize their tolerability. We summarize selected toxicities for ADCs that have been approved through the end of 2020 and three investigational ADCs, which include both payload and linker, as described in the US Prescribing Information, the European Summary of Product Characteristics, and study protocols. These toxicities include peripheral neuropathy; pulmonary, skin, hepatic, and ocular toxicities; hyperglycemia; left ventricular dysfunction; and fluid-related events. We also review the risk minimization approaches to managing these toxicities as described in the product labels and study protocols. Our general observation suggests that the selected toxicities of the approved ADCs are primarily associated with off-target effects of the drug payloads. We also observed that the risk minimization approaches used to manage the selected toxicities are similar across product labels and study protocols. ADCs provide a unique treatment approach that is currently focused on advanced or refractory cancers. The risk minimization approaches for the selected toxicities for the approved ADCs per product label, or the study protocol for those in clinical investigation, are similar to those of standard chemotherapy agents and other pharmaceutical agents for the treatment of advanced malignancies. These risk minimization measures align with standard medical practice and are likely familiar to and feasible for physicians who prescribe for, and to other healthcare practitioners who care for, patients treated with ADCs.