Efficacy and Toxicity of Neoadjuvant Chemotherapy versus Chemo-immunotherapy in Triple-Negative Breast Cancer Patients with and without Germline BRCA Mutations

Background The addition of pembrolizumab (KN522) to neoadjuvant doxorubicin, cyclophosphamide (AC), carboplatin and paclitaxel (TC) has significantly improved survival, albeit with increased toxicity. This study aims to evaluate the effectiveness and toxicity of KN522 and to examine whether treatment outcomes differ in patients with germline BRCA mutations (gBRCAmut). Methods A retrospective analysis of patients with stage II–III triple negative breast cancer, treated at a single tertiary medical center with either KN522 or ACTC. Results Among 100 patients, 51% received ACTC and 49% received KN522; 32% had gBRCAmut. Pathological complete response (pCR) rates were significantly higher with KN522 than ACTC, particularly in gBRCAmut carriers (100% vs 55.6%; OR = 1.8, 95% CI: 1.19–2.72, p = 0.004), but also in non-carriers (64.7% vs 36.7%; OR = 1.76, 95% CI: 1.05-3.00, p = 0.044). Multivariable analysis identified the KN522 protocol (OR 6.28, 95% CI 2.09–18.83; p = 0.001) and gBRCAmut status (OR 3.45, 95% CI 1.06–11.19; p = 0.039) as independent predictors of pCR. Achieving pCR was associated with longer overall survival (HR = 4.13, 95% CI: 1.14–14.94, p = 0.031) and event-free survival (HR = 3.07, 95% CI: 1.08–8.47, p = 0.036). KN522 was also associated with higher hospitalization rates (44.9% vs 13.7%; p < 0.001) and more neutropenic fever (NF) events (30.6% vs 2%; p < 0.001), likely due to lower G-CSF prophylaxis during the AC part of the KN522 protocol (12.2% vs 66.7%; p = 0.009). Conclusions gBRCAmut carriers treated with KN522 achieved a remarkably high pCR rate. KN522 was highly toxic, with nearly half of patients requiring hospitalization, primarily due to NF, supporting the use of primary G-CSF prophylaxis.