Dosing of PD-1 and PD-L1 inhibitors: Cost saving initiatives for significantly decreasing associated expenditure

Abstract

The global immune-oncology drug development pipeline has grown rapidly over recent years. In a survey conducted in August 2019 there were 3,876 active drugs in various stages of development, with programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) among the most common targets.1 Immune checkpoint inhibitors (ICIs) are monoclonal antibodies directed at cytotoxic T lymphocyte-associated protein 4 (CTLA-4), PD-1 or PD-L1. In contrast to cytotoxic drugs, the incidence of adverse effects of the PD-1 and PD-L1 inhibitors are not dose dependent. Consequently, for PD-1 and PD-L1 inhibitors, no recommendations could be derived for a maximum tolerated dose during phase I studies as dose escalation was continued up to the highest planned dose level.2 Preclinical information, including pharmacokinetic (PK) and pharmacodynamic (PD) data, were used to support the choice of the labelled dose.2 Approved PD- 1 and PD-L1 inhibitors were initially developed and approved by the FDA as body weight (BW)-based dosing regimens (nivolumab 3mg/kg every 2 weeks, pembrolizumab 2mg/kg every 3 weeks, avelumab 10 mg/kg every 2 weeks, durvalumab 10 mg/kg every 2 weeks) with the exception of atezolizumab, which was directly approved as a flat dose.2 However, the atezolizumab flat dose was calculated from a BW based dose of 15 mg/kg every 3 weeks in an 80 kg patient.