Dose rationalisation of pembrolizumab and nivolumab using pharmacokinetic modelling and simulation and cost analysis

Pembrolizumab and nivolumab are highly selective anti PD-1 antibodies approved for the treatment of advanced malignancies. Variable exposure and significant wastage have been associated with body size dosing of monoclonal antibodies. The following dosing strategies were evaluated using simulations: body weight, dose banding, fixed dose and pharmacokinetics based method. The relative cost to body weight dosing for band, fixed 150 mg and 200 mg, and pharmacokinetics derived strategies were −15%, −25%, +7% and −16% for pembrolizumab and −8%, −6%, and −10% for band, fixed, and pharmacokinetics derived strategies for nivolumab. Relative to mg/kg doses the median exposures were −1.0%, −4.6% +27.1% and +3.0% for band, fixed 150 mg, fixed 200 mg, and PK derived strategies respectively for pembrolizumab and −3.1%, +1.9% and +1.4% for band, fixed 240 mg, and PK derived strategies respectively for nivolumab. Significant wastage can be reduced by alternative dosing strategies without compromising exposure and efficacy.