Abstract PS2-06-01: Real World Outcomes of the Keynote 522 Regimen for Triple-Negative Breast Cancer

Abstract Introduction: The Keynote 522 study established the use of perioperative chemoimmunotherapy as the standard of care in the treatment of early stage, triple-negative breast cancer, showing benefit in both pathological complete response (pCR) and event-free survival (EFS) when compared to chemotherapy plus placebo. However, the original study did not comment on the racial, ethnic, or socioeconomic characteristics of its participants. This is despite well-documented disparities in breast cancer outcomes for women of color and those of lower socioeconomic status (SES) [1,2]. The purpose of this study was to evaluate real-world outcomes of the Keynote 522 regimen in an NCI-designated, comprehensive cancer center for any heterogeneity in clinical outcomes. Methods: Our study consisted of a single-institution, retrospective analysis of 207 patients with resectable, stage II-III triple negative breast cancer who received care at a combined academic/community hospital network in Northeastern Ohio from 2020-2025, and who received neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab per the Keynote 522 protocol. Patient age, race, ethnicity, insurance provider, poverty index, ECOG score, comorbidity index, menopausal status, primary tumor classification, CPS score, carboplatin schedule (weekly vs q3weeks), LDH level, and immunotherapy-related adverse events were obtained via IRB-approved chart review. The primary outcomes included pCR, EFS, and rates of grade III or higher irAEs. Analysis of pCR and EFS was performed using both univariate and multivariable Cox regression analysis, with multivariable analysis controlling for race, ethnicity, insurance provider, and irAE occurrence and grade. Results: At our institution we identified 207 patients who received KN-522 regimen: 65% self-identified as White, 33% as Black, and 2.1% as Hispanic or Latino. The median poverty index was 16, with 75.4% of patients living above the average national poverty line. Across the entire cohort, a pCR (defined as ypT0/Tis and ypN0) was observed in 60% of patients, compared to 64.8% reported in the Keynote 522 study. Multivariable analysis was performed. Of the evaluated factors, age at diagnosis was the only clinical/demographic factor that significantly correlated with pCR—younger age was associated with higher associated chances of pCR (OR 0.97, 95% CI 0.95-0.99, p-value 0.013). Two-year overall EFS was 82% (95% CI 76-89%). No statistically significant difference in EFS was observed across age, race, ethnicity, poverty index, or insurance provider. Pre-menopausal patients were found to have a significantly higher associated risk of disease recurrence (HR 2.91, 95% CI 1.3-6.51, p-value 0.009), whereas patients who experienced any irAEs were found to have lower associated risk of recurrence (HR 0.37, 95% CI 0.16-0.85, p-value 0.019), though this only held true for patients with grade I/II irAEs vs grade III/IV on subgroup analysis (HR for grade I/II 0.36, 95% CI 0.15-0.89, p-value 0.027; HR for grade III/IV 0.41, 95% CI 0.09-1.78, p-value 0.233). Conclusions: We did not find any socioeconomic or racial heterogeneity with respect to pCR rates in TNBC patients who received neoadjuvant chemo-immunotherapy with the KN-522 regimen. We found that the onset of low-grade irAEs was associated with lower disease recurrence rates, consistent with prior studies showing overall improved PFS and OS in patients who experience irAEs, regardless of cancer type [3]. Overall, this suggests that the data presented in the original Keynote 522 study, which did not comment upon race or other social determinants of health of its participants, appears to reflect observed pCR rates in a real-world setting among TNBC patients. References: 1. doi: 10.1056/NEJMp2200244. 2. doi: 10.1177/107327482513415203. doi: 10.3389/fonc.2021.633032 Citation Format: K. E. Myers, H. Dirawi, M. Lubarsky, M. Stojsavljevic, N. Stabellini, I. Sheng, M. M. Mirsky, A. J.Montero. Real World Outcomes of the Keynote 522 Regimen for Triple-Negative 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 PS2-06-01.