Purpose: The purpose of this study is to evaluate the use and dosing strategies of programmed death protein (PD-1) inhibitors and selected immune-mediated adverse effects within the Veteran’s Health Administration (VHA).
Background: The PD-1 inhibitors, nivolumab and pembrolizumab, are two agents used in the treatment of a number of solid tumors. Their dosing varied in clinical trials supporting a change in FDA approved labeling from weight-based to standardized dosing. While these agents have demonstrated efficacy, immune-mediated adverse-effects (IrAEs) have been associated with their use.
Methods: This is a retrospective review of veterans receiving nivolumab or pembrolizumab for the treatment of solid tumors within the VHA 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 PD-1 inhibitor was categorized into weight-based versus fixeddosing, where possible, and used to identify actual and potential cost-savings opportunities. The incidence of prespecified IrAEs thyroid dysfunction, pneumonitis, and colitis, was quantified and their management was described. Descriptive statistics will be used for the primary and secondary outcomes.
Results: Nivolumab was the primary PD-1 inhibitor utilized for solid tumor treatment. Both nivolumab and pembrolizumab were primarily dosed based on patient weight. For nivolumab orders there was a total of $8,514,300 estimated actual cost savings with $5,591,250 estimated remaining cost-savings potential identified. Of patients who received nivolumab, 514 (15.8%) developed primary hypothyroidism and 299 (9.2%) developed primary hyperthyroidism. At our local institution, one (1.7%) patient developed pneumonitis and one (1.7%) patient developed colitis which was determined to be related to nivolumab therapy.
Conclusions: Nivolumab was the primary PD-1 inhibitor used, with the primary dosing strategy being weightbased. Pembrolizumab dosing was primarily fixed dosing, which may be due to the available vial size(s). There were substantial actual and potential cost-savings opportunities identified. The incidence of the prespecified IrAEs was similar to the incidence currently available in published literature. This supports the recommendation for continued thyroid laboratory monitoring and recognition of signs and symptoms of IrAEs by all health care providers.
