Abstract Introduction: Extended-interval (EI) dosing of pembrolizumab (400 mg IV every 6 weeks) was approved across all solid tumors based on pharmacokinetic modeling and exposure-response analyses. Although EI dosing is more convenient for patients, whether the higher dose and extended dosing interval impacts immune-related adverse events (irAE) and clinical outcomes in patients with breast cancer is unknown. Methods: In this retrospective cohort study, patients with breast cancer treated with pembrolizumab between 2017 to 2024 were included. Safety (irAE) and clinical outcomes including event-free survival (EFS), progression-free survival (PFS) and overall survival (OS) were compared between patients who received only standard dosing (SD; 200 mg IV every 3 weeks) pembrolizumab and those who received ≥ 1 cycle of EI dosing. Results: Of the 355 patients included, 59 (17%) received ≥ 1 cycle of EI pembrolizumab, and 296 (83%) received ≥ 1 cycle of only SD. Of those who received ≥ 1 cycle of pembrolizumab EI, 27 (45.8%) started with 200 mg, 7 (11.9%) started with 400 mg, 9 (15.2%) received only 400 mg, and 16 (27.1%) switched between dosing schedules. The majority (71%) of patients had early-stage disease, and 92% had triple-negative breast cancer. Patients with early-stage disease who received ≥ 1 cycle of EI dosing had lower rates of grade 3 or higher irAE compared to those who received only SD (4% vs. 20%; p=0.01), while rates of any-grade irAE were similar (p=0.3). EFS and OS were similar between the two dosing regimens in patients with early-stage disease (p=0.8 and p=0.5, respectively). In patients with metastatic disease, any-grade irAE (p=0.5), grade 3 or higher irAE (p=0.1), PFS (p=0.8), and OS (p=0.5) were similar between the dosing regimens. Conclusion: This is the first study to demonstrate comparable rates of any-grade irAE and clinical outcomes in patients with breast cancer treated with pembrolizumab EI dosing compared to SD. A lower rate of grade 3 or higher irAE was observed in patients with early-stage breast cancer who received ≥ 1 cycle of EI dosing. As more patients are treated with EI dosing, this data provides new evidence that safety and efficacy are maintained while improving medication burden on patients. Citation Format: A. LeVee, A. Kordic, N. Ruel, J. Mortimer, I. Kang, H. McArthur, M. G. Lechner, K. Tsai. Safety and Clinical Outcomes of Pembrolizumab Standard Dosing Versus Extended-Interval Dosing in Patients with Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-21.
LeVee et al. (Tue,) studied this question.