Use and Toxicity of Checkpoint Inhibitors for Solid Tumor Treatment in a Veteran Population

Abstract

Background: New immunotherapy agents have provided additional options for the treatment of a variety of malignancies, including the programmed death 1 (PD-1) protein inhibitors nivolumab and pembrolizumab. Initial dosing was based on patient weight, but subsequent studies supported fixed dosing, thereby prompting a change in US Food and Drug Administration-approved dosing. Depending on patient weight, one dosing strategy may be more cost-effective than another; thereby, a combination of dosing strategies may be beneficial for institutions. While these agents have been shown to be efficacious, they have been associated with immunerelated adverse events (IrAEs). The purpose of this study was to determine the dosing strategy used and identify actual and potential cost savings, as well as to determine the incidence of hypothyroidism with PD-1 inhibitors in patients of the US Department of Veterans Affairs (VA). Methods: This was a retrospective chart review of VA patients who received a PD-1 inhibitor for the treatment of a solid tumor between January 2015 and July 2017. Data were collected from the VA Corporate Data Warehouse through the VA Informatics and Computing Infrastructure. The dosing strategy for a PD-1 inhibitor was categorized into weight-based vs fixed-dosing where possible and used to identify actual and potential cost-savings opportunities. Thyroid laboratory values and levothyroxine prescriptions were evaluated to determine the overall incidence of the prespecified IrAEs. Descriptive statistics were used for primary and secondary outcomes. Results: Nivolumab was the primary PD-1 inhibitor used for solid tumor treatment. Both nivolumab and pembrolizumab were primarily dosed based on patient weight. Nivolumab orders resulted in $8,514,300 estimated actual cost savings with $5,591,250 estimated missed cost savings identified. Of the patients who received nivolumab, 3249 patients were evaluated for thyroid dysfunction; 514 (15.8%) developed primary hypothyroidism based on laboratory values and levothyroxine prescription data. Conclusions: Utilization of a combination of both weightbased and fixed-dosing strategies for nivolumab has the potential for cost savings, thereby benefiting the health care institution. The incidence of IrAEs identified among patients who received PD-1 inhibitor within the VA health care system was similar to the incidences reported in published literature. This further supports recommendations for close IrAE monitoring and treatment.