Abstract PS4-07-07: Factors associated with pCR and distant recurrence in patients with early-stage TNBC treated with KN522

Abstract Background: The KEYNOTE522 (KN522) regimen of neoadjuvant chemotherapy with pembrolizumab yields statistically significant and clinically meaningful improvements in pathologic complete response (pCR) rate, event-free and overall survival compared to chemotherapy alone in patients with early-stage triple-negative breast cancer (eTNBC). However, one-third of patients (pts) have residual disease, and of these, many develop distant recurrence that contributes to mortality; understanding characteristics of these high-risk pts is a critical unmet need. This study aimed to understand factors associated with (1) achieving pCR with KN522 and (2) in the absence of pCR, developing distant recurrence. Methods: We conducted a retrospective analysis of pts with eTNBC treated at the University of Pennsylvania with the KN522 regimen between September 2021 and December 2023. Multivariate logistic regression analysis was performed to identify variables associated with pCR using the generalized linear model function in R4.5.0. Given sample size restrictions, Fisher’s exact test was used to evaluate variables associated with recurrence. For these analyses, exact odds ratios and 95% confidence intervals are reported. Results: 225 pts with eTNBC initiated KN522 during the study period. 222 had surgery; 120 (54%) had pCR (no invasive cancer) and 102 (46%) had residual disease. At a median follow-up of 28 months, 26 pts (12%) including 2 with pCR developed distant recurrence. Factors significantly associated with achieving pCR were tumor grade 3 (vs 2; OR 3.42, 95% CI 1.31-9.84, p=0.016) and development of an immune-related adverse event (IRAE vs no IRAE, OR 2.26, 95% CI 1.05-5.07, p=0.041). Factors negatively associated with pCR included clinical stage III (vs I/II, OR 0.50, 95% CI 0.26-0.92, p=0.028) and older age at diagnosis (OR 0.97, 95% CI 0.94-0.99, p=0.047). Among patients who did not achieve pCR, factors associated with distant recurrence were pathologic (p)N stage (N1+ vs N0, OR 19.83, 95% CI 5.58 - 91.85, p0.0001), pT stage (T2+ vs T0/T1, OR 4.50, 95% CI 1.54-13.53, p=0.003), and clinical stage III (vs I/II, OR 4.25, 95% CI 1.42-14.58, p=0.005). Conclusions: This real-world analysis reinforces established factors associated with pCR including tumor grade and clinical stage. Moreover, these results add to growing evidence across solid tumors that the development of IRAEs correlates with improved response. Among patients with residual disease after KN522, those with node positivity, pT2 or larger tumors, and stage III disease may represent target populations for studies investigating enhanced surveillance and treatment strategies, such as with circulating tumor DNA and antibody-drug conjugates. Citation Format: R. Jaber Chehayeb, P. Coutifaris, F. White, J. Heintz, S. L. Jacob, J. Q. Zhang, O. M. Fayanju, E. S. Lebrow, N. Taunk, K. Lee, H. Knollman, I. Makhlin, A. Clark, R. Jankowitz, A. Nayak, S. Domchek, A. DeMichele, P. D. Shah. Factors associated with pCR and distant recurrence in patients with early-stage TNBC treated with KN522 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 PS4-07-07.