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.
背景：帕博利珠单抗联合新辅助化疗可显著提高早期三阴性乳腺癌（TNBC）的病理完全缓解率（pCR），但在真实世界环境中，治疗强度及基线临床因素的影响尚未得到充分探讨。 方法：本研究回顾性纳入了2022年1月至2025年1月期间，在意大利11家肿瘤中心连续接受KEYNOTE-522方案治疗的169例II–III期TNBC患者。收集了临床、病理及治疗数据，包括相对剂量强度（RDI）、剂量调整及毒性反应。主要终点为pCR（定义为ypT0/is ypN0）。 结果：总体pCR率为65.7%，与临床试验数据一致。40%的患者出现剂量下调，18%的患者中止化疗。维持RDI ≥85%的患者pCR率更高（79.3% vs. 51.2%，p < 0.001）。同样，未进行剂量下调的患者（72.5% vs. 55.2%，p = 0.031）以及完成全部化疗周期的患者（73.1% vs. 41.0%，p < 0.001）疗效更优。剂量调整主要发生在紫杉类/卡铂治疗阶段，主要原因包括血液学毒性（贫血44%、中性粒细胞减少30%、血小板减少15%）、神经病变（18%）和胃肠道事件（36%）。较高的肿瘤浸润淋巴细胞（TILs）水平与pCR率提高相关（70.6% vs. 60.7%，p = 0.049），而BRCA突变也显示出有利趋势。ECOG评分、BMI、妊娠史及合并症与pCR无显著相关性。 结论：在这一多中心真实世界队列中，维持化疗剂量强度（RDI ≥ 85%）并完成所有计划周期与更高的pCR率显著相关，这进一步强调了在基于帕博利珠单抗的TNBC新辅助治疗中，尽量减少剂量下调和中止治疗的重要性。
肿瘤(癌症)患者之家