Abstract
Background: Pembrolizumab combined with neoadjuvant chemotherapy significantly improves pCR in early TNBC, but the effect of treatment intensity and baseline clinical factors has been insufficiently explored in real-world settings. Methods: We retrospectively included 169 consecutive patients with stage II-III TNBC treated across 11 Italian oncology centers (January 2022-January 2025) with the KEYNOTE-522 regimen. Clinical, pathological, and treatment data were collected, including relative dose intensity (RDI), dose modifications, and toxicities. The primary endpoint was pCR (ypT0/is ypN0). Results: The overall pCR rate was 65.7%, which is consistent with clinical trial data. Dose reductions occurred in 40% of patients and chemotherapy was discontinued in 18%. Patients maintaining RDI ≥85% achieved higher pCR (79.3% vs. 51.2%, p < 0.001). Similarly, patients without dose reductions (72.5% vs. 55.2%, p = 0.031) and those completing all cycles (73.1% vs. 41.0%, p < 0.001) had superior outcomes. Dose modifications occurred mainly during the taxane/carboplatin phase and were predominantly due to hematological toxicities (anemia 44%, neutropenia 30%, and thrombocytopenia 15%), neuropathy (18%), and gastrointestinal events (36%). Higher TILs correlated with increased pCR (70.6% vs. 60.7%, p = 0.049), while BRCA mutations showed a favorable trend. ECOG, BMI, pregnancy history, and comorbidities were not significantly associated with pCR. Conclusions: In this multicenter real-world cohort, maintaining chemotherapy dose intensity (RDI ≥ 85%) and completing all planned cycles were strongly associated with higher pCR rates, reinforcing the clinical importance of minimizing dose reductions and discontinuations during pembrolizumab-based neoadjuvant therapy for TNBC.