(BSPOT43) Real-world overall survival after alternative dosing for pembrolizumab in the treatment of non-small cell lung cancer: a nationwide retrospective cohort study with a non-inferiority primary objective.

Background: Early clinical trials and pharmacological studies show comparable results with pembrolizumab doses lower than the approved 200 mg every three weeks. Following a recommendation from the Dutch Society of Medical Oncology, many Dutch hospitals implemented an alternative, partially lower, weight-based dosing regimen for pembrolizumab.

Objectives: This analysis compares the overall survival (OS) of the alternative pembrolizumab dosing regimen to standard dosing using a nationwide registry in non-small cell lung cancer (NSCLC) patients.

Methods: This is a retrospective cohort study with a non-inferiority primary objective. Forty hospitals in the Dutch Medication Audit and Dutch Lung Cancer Audit treated 1966 patients with NSCLC with first line pembrolizumab (mono- or combination therapy) between Jan 1st, 2021 and Mar 31st, 2023. Alternative weight-based pembrolizumab dosing (100/150/200 mg Q3W or 200/300/400 mg Q6W) was administered to 604 patients, and 1362 patients received standard pembrolizumab dosing (200 mg Q3W or 400 mg Q6W). A Cox proportional hazard model with selected covariates was used to compare the OS between alternative and standard dosing regimens. The non-inferiority margin was set at an upper limit of the 95% confidence interval (95%CI) of the hazard ratio (HR) for OS < 1.2.

Results: Distribution of age (66.7 years +/-9.4), sex (45% female), and treatment combinations were similar for both groups, comorbidity score was higher in the standard dosing group. Median daily dose in the alternative dosing group was 22% lower compared to the standard dosing group, 7.14 mg/day (interquartile range (IQR): 5.48-8.04 mg/day) vs. 9.15 mg/day (IQR: 8.33-9.52 mg/day), respectively. The OS of the alternative dosing regimen was non-inferior compared to standard dosing (adjusted HR 0.83, 95%CI: 0.69-1.003).

Conclusions: This large, retrospective real-world analysis supports the hypothesis that the alternative, partially lower pembrolizumab dosing protocol in NSCLC maintains treatment effectiveness while reducing treatment costs.