PURPOSE Pembrolizumab, a PD-1 immune checkpoint inhibitor (ICI), is a standard first-line treatment for advanced non–small cell lung cancer (NSCLC). Although fixed-dose pembrolizumab (200 mg once every 3 weeks) is widely used based on pharmacokinetic modeling, its clinical equivalence to weight-based dosing (2 mg/kg once every 3 weeks) in real-world populations remains uncertain. METHODS We conducted a retrospective cohort study of 414 patients with advanced NSCLC treated with pembrolizumab at a single center between 2016 and 2021. Patients received either fixed-dose or weight-based pembrolizumab. Overall survival (OS) was the primary outcome; secondary outcomes included immune-related adverse events (irAEs). To address baseline imbalance and confounding, inverse probability of treatment weighting was applied to balance baseline characteristics, followed by multivariable Cox regression and subgroup analyses adjusting for clinical and demographic factors. RESULTS Of 414 patients, 339 (81.9%) received fixed dosing and 75 (18.1%) received weight-based dosing. Median OS was similar between fixed-dose and weight-based cohorts (18.4 v 23.2 months; hazard ratio 0.73 95% CI, 0.49 to 1.10; P = .11). Rates of grade ≥2 irAEs did not differ significantly between groups ( P = .52). No OS differences were observed between dosing strategies when stratified by treatment regimen (ICI monotherapy v ICI-platinum doublet). Within the weight-based dosing cohort, survival was comparable across body mass index categories and body weight tertiles. In multivariable analyses, Eastern Cooperative Oncology Group performance status and the number of treatment cycles were independently associated with survival, whereas dosing strategy was not. CONCLUSION Weight-based and fixed-dose pembrolizumab demonstrated comparable effectiveness and safety in real-world patients with NSCLC. Weight-based dosing may represent a sustainable cost-effective alternative, particularly in underweight patients and in resource-limited settings, without compromising clinical outcomes, supporting further evaluation in prospective studies.
Shachar et al. (Wed,) studied this question.