Abstract PS4-10-27: Tolerability of the KEYNOTE-522 regimen in a diverse real-world cohort of patients with early triple negative breast cancer (TNBC)

Abstract Background: The KEYNOTE-522 trial demonstrated a significant improvement in efficacy with neoadjuvant chemotherapy (NACT) in combination with pembrolizumab compared to chemotherapy alone for patients (pts) with early TNBC. Real-world data on the toxicity of this regimen is limited, especially in racially diverse populations. Our study aims to describe the toxicity of the KEYNOTE-522 regimen in a diverse, urban population at a large tertiary referral center, and evaluate the impact of race/ethnicity and age on tolerability of the regimen. Methods: We performed a retrospective chart review of pts with anatomic Stage II-III TNBC who received the KEYNOTE-522 regimen within our health system from August 2021 to February 2025. Pts who received /= 1 cycle of NACT and pembrolizumab were included. Toxicity was measured by the rates of dose reductions, drug discontinuations, treatment (tx) delays, hospitalizations, and ED visits due to treatment-related AEs (TRAEs). Descriptive statistics were used to describe patient data, and non-parametric tests were utilized in the stratified analyses by race/ethnicity and age. Results We included 111 pts who had a median age of 55 years. Most patients had Stage II (81%) and lymph node negative (52%) BC. Overall, 32% of pts were White, 26% Black, 14% Asian, 16% Hispanic, and 11% Other. Among all pts, 19% (N=21) had dose reductions, and 55% (N=61) had tx delays due to toxicity. 33% (N=36) of pts discontinued one or more agents early, with 14% (N=16) discontinuing pembrolizumab. Hospitalizations and ED visits due to AEs were reported in 33% (N=36) and 28% (N=31) of pts, respectively. There were no significant differences in the rates of dose reductions, drug discontinuations, tx delays, hospitalizations, or ED visits when stratified by race/ethnicity (Table 1). Asian (25%) and White (17%) pts had higher rates of pembrolizumab delays due to irAEs compared to Black (7%) and Hispanic (0%) pts, but this difference was not statistically significant (p=0.051). When stratified by age, 40 years (N=18), 40-65 years (N=67), and 65 years (N=26), there were no significant differences in toxicity though pts 40 years had higher rates of ED visits (44%) and hospitalizations (44%) for irAEs than pts 40-65 years (10% and 15%, respectively, p=0.006) and pts 65 years (23%, p=0.036). Conclusion: In a diverse patient population, the observed drug discontinuation rate of the KEYNOTE-522 regimen was 33%, notably higher than the 23% reported in the KEYNOTE-522 trial. In our real-world study, one-third of pts were hospitalized and more than half had treatment delays due to TRAEs, highlighting the toxicity of the regimen. There were no significant differences in tolerability based on race/ethnicity. The higher rates of ED visits and hospitalizations due to irAEs in younger pts should be evaluated in future studies. Citation Format: J. Anderson, E. Baldwin, J. Dejesus, G. Van Hyfte, P. Pandu, N. Krishnamurthy, M. Rattu, R. Farley, R. Patel, A. Tiersten. Tolerability of the KEYNOTE-522 regimen in a diverse real-world cohort of patients with early triple negative breast cancer (TNBC) 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 PS4-10-27.