Abstract Background: The KEYNOTE-522 (K522) study demonstrated that the addition of pembrolizumab immune therapy to anthracycline- and taxane-based chemotherapy improves pathological complete response (pCR) rate, event-free survival, and overall survival in high-risk early TNBC. However, the optimal treatment strategy for patients with smaller node-negative tumors who do not meet K522 eligibility criteria is not known, and regimens that mitigate the risk of anthracycline-mediated toxicity in lower risk populations are being evaluated. To explore the efficacy of K522 versus a non-anthracycline approach, we conducted a retrospective cohort study comparing pCR rates in patients with lower risk early TNBC (T1-T2 and N0) who received K522 versus a non-anthracycline regimen.. We further investigated the role of the presence of Tumor Infiltrating Lymphocytes (TILs) and response to neoadjuvant chemoimmunotherapy between treatment groups, given earlier studies which have indicated their potential use as a predictive biomarker of treatment response. Methods: From institutional databases, we reviewed 271 cases of TNBC and identified 83 diagnosed with clinical T1-T2 N0 TNBC between June 2021 and December 2024 at two academic sites—UT Southwestern Medical Center (UTSW) and Parkland Memorial Hospital (PH). Imaging and pathology reports at diagnosis and at time of surgery were evaluated for all cases, as well as chemoimmunotherapy records. All cases had ER positive staining of ≤ 1%, PR staining of ≤5%, and HER2 staining of 0-2 with negative FISH results in those cases with 2+ staining. Presence of TILs within the tumor biopsy pathology report was considered positive, and its association with pCR was assessed. Standard statistical analyses were performed viaunivariate logistic regression and simple linear regression in Graphpad Prism. Results: Among the 83 patients evaluated, 51 (61.4%) achieved a pathologic complete response; 34 of the 59 (57.6%) patients who received the K522 regimen achieved pCR, while 17 of the 24 (70.8%) patients who received the non-anthracycline regimen achieved a pCR (p = 0.45). This was not due to differences in grade (p=.11), clinical stage (p=.36), or ki-67 (p=.54). TILs were reported in 33 patients (39.8%), of whom 25 received the entire K522 regimen (42.4% of this treatment group) and 8 received the non-anthracycline regimen (33.3% of this group). Presence of TILs was significantly associated with pCR (p = .032) with 75.8% of cases achieving pCR while only 52% achieved pCR in the negative TIL cases. This was not due to differences in grade (p=.54), clinical stage (p=.98), or ki-67 (p=.34). Conclusions: While this is a small retrospective study of 83 patients, our findings suggest that in selected patients with early-stage TNBC (T1-T2, N0), a neoadjuvant non-anthracycline regimen combining carboplatin, paclitaxel, and pembrolizumab can achieve pCR rates comparable to the full K522 regimen. While the pCR rates in this study was not-significant between the K522 and non-anthracycline groups, this may be due to small sample size, or to the comparable response of early TNBC to either regimen, and further study is warranted. These results are consistent with prior prospective studies, including NeoPACT and CALGB40603, that demonstrate comparable pCR rates with platinum- and taxane-based regimens in early TNBC. Furthermore, TILs continue to show promise as a predictive biomarker of treatment response and may play an important role in tailoring treatment recommendations for select patients. Further studies are warranted in order to delineate the most effective treatment approach in these patients. Citation Format: A. K. Mennie, J. Thomas, S. Kanjwal, S. Reddy, G. Delgado Ramos, B. Santos, N. Sadeghi, H. McArthur, N. Unni. Real-world efficacy of non-anthracycline neoadjuvant chemo-immunotherapy in early-stage triple negative breast cancer: a retrospective two site cohort study 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 PS4-10-12.
Mennie et al. (Tue,) studied this question.