Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted treatment options. Immunotherapy has recently emerged as a potential strategy. The addition of pembrolizumab to neoadjuvant chemotherapy, as established in the KEYNOTE-522 trial, represents a major advancement in targeted immunotherapy for TNBC. However, real-world data validating its feasibility and outcomes remain limited. This study aims to evaluate, in real-life settings, the impact of adding pembrolizumab to neoadjuvant chemotherapy on complete pathological response (pCR), recurrence-free survival (RFS), and overall survival (OS) in patients with non-metastatic TNBC. Methods: This retrospective cohort study included patients treated at King Hussein Cancer Center (KHCC) between 2015 and 2022. Among 8523 breast cancer cases, 761 were TNBC. Eligible patients had non-metastatic TNBC, received neoadjuvant therapy, and underwent surgery. The immunotherapy group included patients treated with neoadjuvant pembrolizumab (2019–2022); the no-immunotherapy group received standard neoadjuvant chemotherapy (2015–2022). Propensity score matching (1:1, nearest neighbor) was performed based on pre-treatment covariates including age, BMI, clinical stage, comorbidities, smoking, and histopathology. Pathological response, complication rates, RFS, and OS were analyzed using logistic regression and Kaplan–Meier curves with log-rank testing. Results: The matched cohort included 130 patients (65 per group). The study groups’ baseline characteristics were well-balanced between the two groups. Postoperative complication rates were similar across groups, with no significant increase in adverse events observed in the immunotherapy group. The mean lymph node positivity ratio was significantly lower in the immunotherapy group (2.2 ± 7.7 vs. 24.3 ± 33.1,p< 0.001), indicating reduced nodal burden. Pathologic complete response (pCR) was markedly higher with immunotherapy (66.2% vs. 9.2%,p< 0.001). However, survival outcomes were significantly improved with immunotherapy. At three years, RFS was markedly higher in the immunotherapy group (91.8%; 95% CI: 85.0–99.0%) compared to the no-immunotherapy group (53.8%; 95% CI: 42.8–67.8%), with a log-rankp< 0.001. Overall survival also significantly favored the immunotherapy group, with three-year OS of 87.2% versus 67.8% in no-immunotherapy group (p= 0.0015). Conclusions: Neoadjuvant pembrolizumab significantly enhances pathological response, reduces nodal involvement, and provides durable RFS and OS benefits in non-metastatic TNBC without increasing perioperative complications. This study supports incorporating immunotherapy into standard neoadjuvant regimens for TNBC patients and provides real-world evidence from a Middle Eastern tertiary cancer center.
背景：三阴性乳腺癌（TNBC）是一种侵袭性亚型，靶向治疗选择有限。免疫疗法近年来已成为一种潜在的治疗策略。根据KEYNOTE-522试验确立的方案，在新辅助化疗基础上加用帕博利珠单抗，代表了TNBC靶向免疫治疗领域的重大进展。然而，验证其可行性和疗效的真实世界数据仍然有限。本研究旨在真实世界环境中，评估在新辅助化疗基础上加用帕博利珠单抗对非转移性TNBC患者病理完全缓解（pCR）、无复发生存期（RFS）和总生存期（OS）的影响。 方法：这项回顾性队列研究纳入了2015年至2022年间在侯赛因国王癌症中心（KHCC）接受治疗的患者。在8523例乳腺癌病例中，761例为TNBC。符合条件的患者为非转移性TNBC，接受了新辅助治疗并接受了手术。免疫治疗组包括接受新辅助帕博利珠单抗治疗的患者（2019–2022年）；非免疫治疗组接受标准新辅助化疗（2015–2022年）。根据治疗前的协变量（包括年龄、BMI、临床分期、合并症、吸烟史和组织病理学）进行倾向评分匹配（1:1，最近邻法）。使用逻辑回归和Kaplan-Meier曲线（对数秩检验）分析病理反应、并发症发生率、RFS和OS。 结果：匹配后的队列包括130名患者（每组65名）。两组研究人群的基线特征均衡。术后并发症发生率在各组间相似，免疫治疗组未观察到不良事件显著增加。免疫治疗组的平均淋巴结阳性率显著降低（2.2 ± 7.7 vs. 24.3 ± 33.1, p < 0.001），表明淋巴结负荷减轻。免疫治疗组的病理完全缓解率（pCR）显著更高（66.2% vs. 9.2%, p < 0.001）。此外，免疫治疗显著改善了生存结局。三年时，免疫治疗组的RFS（91.8%；95% CI：85.0–99.0%）显著高于非免疫治疗组（53.8%；95% CI：42.8–67.8%），对数秩检验p < 0.001。总生存期也显著有利于免疫治疗组，三年OS为87.2%，而非免疫治疗组为67.8%（p = 0.0015）。 结论：新辅助帕博利珠单抗在不增加围手术期并发症的情况下，显著提高了非转移性TNBC患者的病理缓解率，减少了淋巴结受累，并提供了持久的RFS和OS获益。本研究支持将免疫疗法纳入TNBC患者的标准新辅助治疗方案，并提供了来自中东地区三级癌症中心的真实世界证据。
肿瘤(癌症)患者之家