Evaluating the efficacy and safety of immune checkpoint inhibitors by detecting the exposure-response: An inductive review

Immune checkpoint inhibitors (ICIs) have been demonstrated an effective treatment in multiple tumor type, which restore the immune response to against cancer cell. Currently, approved ICIs include anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4); anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) monoclonal antibodies (mAbs). In most these drugs, unique pharmacokinetic (PK) and pharmacodynamics (PD) have shown significant influence on clinical outcomes, which occurred by target-mediated drug concentration and time-varying drug clearance. An exposure-response (E-R) relationship has been used to describe the safety and efficacy of ICIs, and shown a plateaued E-R and time dependent changes in exposure. Using an enzyme linked immunosorbent assay (ELISA) or LC-MS/MS method to measure the peak concentration, trough concentration or area under the curve (AUC) of ICIs to assess the drug exposure. There are lots of covariates that have an influence on exposure, such as sex, clearance, body weight and tumor burden. In this review, we pooled data from studies of concentration or other pharmacokinetics parameter of mAbs to assess E-R in efficacy and safety.