e23264 Background: Immune checkpoint inhibitors lack a dose-response relationship, allowing optimisation of dosing strategies that may reduce drug use. Pembrolizumab received its initial regulatory approval for the treatment of non-small cell lung cancer (NSCLC) at weight-based dosing (2 mg/kg every 3 weeks (Q3W)), as employed in pivotal clinical trials demonstrating its efficacy and safety. This dosing regimen was later replaced by the currently approved flat-dosing (200 mg Q3W or 400 mg Q6W) in all indications, potentially increasing drug use. This retrospective observational study evaluates differences in pembrolizumab use for different dosing strategies in a real-world patient cohort. Methods: Overall, 124 advanced NSCLC patients, treated with first-line pembrolizumab monotherapy at a single institution, were included. During the observation period, pembrolizumab flat-dosing was employed, with possible extensions of treatment administrations. Patient and treatment data were obtained from medical records. Duration of treatment was calculated from day 1 of first cycle to last day of last cycle, excluding treatment delays due to adverse events. Pembrolizumab use was calculated for 3 dosing strategies: i) as actually received, ii) as flat-dosing, iii) as body-weight dosing, capped at 200 mg Q3W. It is presented as median dose Q3W and cummulative dose in the whole cohort. Results: Included patients had a median weight of 73 kg (IQR: 65-84) and received a total of 1600 mg of pembrolizumab (IQR: 800-3600) over 24 weeks (IQR: 12-60). The median pembrolizumab dose was i) 190 mg Q3W (IQR: 172-200) as actually received by patients, and would be ii) 200 mg Q3W (IQR: 200-200) in case of flat dosing, and iii) 146 mg Q3W (IQR: 130-168) in case of body-weight dosing. Overall, total pembrolizumab dose in the whole cohort was i) 283,600 mg actually used, and would be ii) 327,800 mg in flat-dosing, and iii) 251,200 mg body-weight dosing, resulting in a 23.4% reduction of drug use in weight-adjusted vs flat-based dosing. Conclusions: Pembrolizumab dosing adjusted to body weight, as initially approved, would reduce drug use vs the currently approved flat-dosing, reaching nearly a 25% reduction in our cohort of patients.