Abstract PS4-07-12: Real-world comparison of pembrolizumab dosing schedules (q3w vs q6w) in early TNBC: Insights from the PETRHA cohort

Abstract Pembrolizumab combined with neoadjuvant chemotherapy has become the standard of care for most patients with early-stage triple-negative breast cancer (TNBC), typically administered at a dose of 200 mg every three weeks (q3w), as studied in the KEYNOTE-522 trial. A 400 mg every six weeks (q6w) dosing schedule was subsequently approved by regulatory agencies based on pharmacokinetic modeling and exposure-response analyses demonstrating comparable drug exposure and similar expected efficacy and safety to the standard q3w regimen. Although the q6w schedule was not evaluated in prospective neoadjuvant trials, its adoption has increased in real-world practice, particularly in settings with logistical constraints. However, comparative clinical data on the safety and efficacy of q6w versus q3w dosing in early TNBC remain limited. Patients with early TNBC who received neoadjuvant chemotherapy and pembrolizumab within the PETRHA retrospective cohort were included. Pembrolizumab was administered either 200 mg every three weeks (q3w) or 400 mg every six weeks (q6w), based on physicians' choice and local practice. Patients receiving q3w and q6w dosing were compared in terms of treatment completion (defined as receipt of all planned neoadjuvant pembrolizumab cycles), immune-related adverse events (irAEs), and pathologic complete response (pCR) rates, defined as ypT0/is ypN0. Descriptive statistics were used to summarize baseline characteristics. Categorical variables were compared using chi-square or Fisher’s exact tests. A two-sided p-value <0.05 was considered statistically significant. A total of 304 patients were included, of whom 232 (76.3%) received pembrolizumab 200 mg q3w, and 72 (23.7%) received 400 mg q6w. Most patients had stage II (53.9%) or stage III (42.1%) disease, with a similar clinical stage distribution across dosing groups. The use of the q6w schedule was significantly more common in public healthcare settings, with only 0.6% of patients in private institutions receiving pembrolizumab q6w compared to 51.1% in public centers (p<0.001). Treatment completion rates were comparable, with 75.7% of patients in the q3w group and 76.4% in the q6w group completing all planned neoadjuvant pembrolizumab cycles (p=0.60). The pCR rate was higher in the q3w group (62.5%) compared to the q6w group (51.4%), although this difference did not reach statistical significance (p=0.093). irAEs occurred in 37.6% of patients receiving q3w and 25.0% of those receiving q6w dosing (p=0.051), with no statistically significant differences in grade 3 or higher irAEs (12.8% vs. 0%, p=0.205), In this real-world cohort of Hispano-American women with early TNBC, the use of a q6w neoadjuvant pembrolizumab dosing schedule was associated with similar treatment completion rates and a non-significantly lower pCR rate compared to the standard q3w neoadjuvant regimen. The numerically lower incidence and severity of irAEs with q6w dosing suggest a potentially favorable toxicity profile, although the difference was not statistically significant. These findings support the feasibility of q6w neoadjuvant pembrolizumab dosing in clinical practice. Citation Format: A. Aranda-Gutierrez, D. Vazquez-Juarez, Y. Chavarri-Guerra, F. Petracci, O. Peña-Curiel, F. Acevedo, E. Zamudio Lozoya, L. Gonzalez Gonzalez, W. Mantilla, S. Franco, M. Bravo, P. Herrera Ríos, C. Arce Salinas, K. Centelles López, H. Gomez, P. Carreon, E. Aguirre Alvarez, B. Martinez-Cannon, A. Lopez-Galindo, M. Garcia Garces, E. Willars, E. Korbenfeld, A. Benitez-Cruz, M. Lema, C. Lema, C. Villarreal-Garza. Real-world comparison of pembrolizumab dosing schedules (q3w vs q6w) in early TNBC: Insights from the PETRHA cohort [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 PS4-07-12.