Efficacy and toxicity of pembrolizumab in addition to neoadjuvant platinum-based chemotherapy (NAPC) in triple-negative breast cancer (TNBC) patients with and without germline BRCA mutations (gBRCAmut).

e12611 Background: TNBC is an aggressive disease with high rates of metastatic recurrence. The addition of Pembrolizumab to NAPC has significantly improved pathological complete response (pCR), event-free survival (EFS) and overall survival (OS), albeit with increased toxicity. We compared the efficacy and toxicity of NAPC (doxorubicin and cyclophosphamide followed by carboplatin and paclitaxel (ACTC protocol)), and the KN522 protocol (ACTC protocol, concurrent with pembrolizumab), particularly between gBRCAmut and gBRCA wild type (gBRCAwt) patients. Methods: a single institution retrospective analysis of stage II/III TNBC patients treated with either the ACTC or the KN522 protocols, between 2015-2024. A binary logistic regression model was used for odds ratio (OR) estimation. A univariate Cox regression analysis was used for survival analyses. Due to differences in follow-up durations for the different protocols, follow-up time was limited to 50 months for the OS analysis. Results: Among 100 included patients, 51% received ACTC and 49% received KN522. Sixty-four (64%) were gBRCAwt and 32 (32%) had gBRCAmut. pCR rates were Significantly higher with KN522 compared to ACTC (72.5% vs 45.1%, OR=3.37, p=0.004, 95% CI:1.45–7.81). Patients with gBRCAmut treated with the KN522 protocol exhibited significantly higher pCR rates compared to those with gBRCAwt (100% vs 64.7%, OR=1.64, p=0.010, 95% CI: 1.12-1.26). Higher pCR rates were also observed among patients with gBRCAmut under the ACTC protocol (55.6% vs 36.7%, p=0.20). Patients in the KN522 group had significantly longer OS compared to the ACTC group (HR=0.11, 95% CI: 0.01–0.87, p=0.037). Additionally, patients who achieved pCR had a significantly longer OS and EFS compared to patients who did not (HR=0.24, 95% CI: 0.07–0.89, p=0.033 and HR=0.32, 95% CI: 0.11–0.92, p=0.035 respectively). No significant differences were observed in overall adverse event (AE) rates or protocol interruptions rates between the protocols. However, patients treated with KN522 experienced significantly more hospitalizations and neutropenic fever (NF) events compared to patients treated with ACTC (44.9% vs 13.7%, OR=5.12, 95% CI: 1.93-13.59, p=0.001 and 30.6% vs 2%, OR=2.38, 95% CI: 1.86-3.04, p<0.001, respectively). In addition, 76% of patients treated with the KN522 protocol experienced immune related AEs (ir-AEs) with 12% G3-4 ir-AEs. Conclusions: patients treated with the KN522 regimen achieved higher pCR rates compared to those on the ACTC protocol, with a 100% pCR rate among gBRCAmut patients treated with KN522. The KN522 regimen was associated with significantly more hospitalizations, primarily due to NF. Further research is needed to explore biomarkers for immunotherapy toxicity and efficacy among patients with gBRCAmut and gBRCAwt.