Model-informed approaches to develop drug cost-saving dosing strategies for pembrolizumab

Background The increasing use of pembrolizumab in oncological treatments results in substantial healthcare costs. The recently approved subcutaneous (SC) pembrolizumab formulation remains expensive. The aim of this study was to evaluate alternative SC pembrolizumab dosing strategies that reduce costs while maintaining equivalent exposure and improving convenience. Methods A previously published population pharmacokinetic model was used to evaluate alternative dosing strategies achieving exposure equivalent to the intravenous (IV) 2 mg/kg Q3W dosing (reference) compliant with FDA guidelines and reducing costs. First, extended fixed dosing intervals irrespective of bodyweight were investigated. Second, body-weight-adjusted dosing intervals were evaluated. Finally, we explored to inject SC formulation (790 mg) intravenously. Results Identified alternative regimens included SC 790 mg Q7W for all patients; SC 790 mg Q8W ('55 kg), 790 mg Q7W (55–85 kg), and 790 mg Q6W ('85 kg); and IV administration of 790 mg Q9W using the SC formulation. The extended-interval SC regimen (790 mg Q7W) would reduce annual cost to €85,000 (-14%). A bodyweight-adjusted SC strategy would reduce yearly cost from €99,166 to €85,000 (-14%; 55–85 kg) and to €74,375 (-25%; '55 kg). Using the SC formulation intravenously can potentially save annual costs by €33,055 (-33%). In addition, extracting 5 doses of 150 mg Q3W out of one 790 mg SC dose could reduce the annual costs even to €39,666 (-60%). Conclusions Dose interval extension of subcutaneous pembrolizumab maintains equivalent exposure and complies with regulatory requirements. Intravenous administration of the subcutaneous formulation is a promising highly cost-effective intervention but requires prospective safety investigation before implementation.