化疗剂量强度对帕博利珠单抗治疗的早期三阴性乳腺癌病理完全缓解的影响：一项真实世界多中心分析

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.