标准与规范丨三阴性乳腺癌免疫检查点抑制剂临床应用专家共识（2025版）

专家共识 肿瘤科 · 2025 · 中华医学杂志
乳腺肿瘤三阴性乳腺癌免疫检查点抑制剂临床应用专家共识

一、共识制订方法学

本共识由中国医药教育协会肿瘤药物临床研究专家委员会和中国初级卫生保健基金会乳腺癌专业委员会牵头组织编写，联合相关领域专家共同完成。通过问卷调查和研讨，明确制订本共识的必要性，并围绕TNBC免疫治疗现状，提出了新辅助治疗、辅助治疗和晚期治疗治疗中ICI适用人群、疗效、安全性、不良反应和生物标志物等关键问题。在PubMed、万方数据库和中国知网等数据库以“triple negative breast cancer”“treatment”“immune checkpoint inhibitor”“三阴性乳腺癌”“治疗”“免疫检查点抑制剂”等为关键词检索2000年1月至2025年1月期间发表的相关文献，获取TNBC免疫治疗的全部文献信息。组建由49位专家（涵盖乳腺外科、乳腺内科和肿瘤科）组成的共识编写团队，经过8次线上和1次线下会议，深入探讨共识的框架和临床治疗难点。按照关键问题完成分工后，由4名成员分别执笔各部分内容，然后进行整理和精简成文。参照牛津大学循证医学中心临床证据水平分级，形成不同强度的推荐意见（ 表1 ）。最后由该49名专家对共识的关键性问题进行线上投票表决。本指南已在国际实践指南注册平台注册（注册号：PREPARE-2025CN787）。

二、ICI在TNBC中的临床应用

（一）PD-1/PD-L1抑制剂在TNBC新辅助治疗中的应用 既往已开展大量临床研究探讨了PD-1/PD-L1抑制剂在早期TNBC中的应用效果。Ⅰb期研究KEYNOTE-173最早探索了帕博利珠单抗联合新辅助化疗在高危、早期、非转移性TNBC患者中的安全性和初步抗肿瘤活性 ［ 2 ］ ，其初步结果显示，帕博利珠单抗在TNBC新辅助治疗中的病理完全缓解（pCR）率达到60%，且PD-L1的CPS、治疗前与治疗中的肿瘤间质浸润淋巴细胞（sTIL）与pCR率显著相关。GeparNuevo研究探索了度伐利尤单抗联合白蛋白结合型紫杉醇+表柔比星/环磷酰胺方案在TNBC新辅助nabP-EC方案中的疗效，结果显示，度伐利尤单抗联合化疗产生了更高的pCR率（53.4%比44.2%，OR=1.53，95%CI：0.82~2.84，P=0.182），而且可显著改善患者的长期生存：3年无侵袭性疾病生存率（iDFS）提升了8.4%（85.6%比77.2%，HR=0.48，95%CI：0.24~0.97，P=0.039 8），3年远处无病生存率（DDFS）提升了13.3%（91.7%比78.4%，HR=0.48，95%CI：0.24-0.97，P=0.039 8），3年总生存率提升了11.7%（95.2%比83.5%，HR=0.48，95%CI：0.24~0.97，P=0.039 8）［ 3 ］ 。NeoTRIPaPDL1研究在接受卡铂+白蛋白结合型紫杉醇新辅助化疗的基础上联合阿替利珠单抗后，患者并未显著提高pCR率（43.5%比40.8%，OR=1.11，95%CI：0.69~1.79，P=0.066）［ 4 ］ 。IMpassion 031研究显示阿替利珠单抗联合新辅助化疗（白蛋白结合型紫杉醇，序贯阿霉素+环磷酰胺）组在意向性分析（ITT）人群（57.6%比41.1%，单侧P=0.004 4）和PD-L1阳性患者（68.8%比49.3%，P=0.021）中的pCR率都得到了大幅提高；长期随访也显示阿替利珠单抗组的无事件生存期（EFS）、无疾病生存期（DFS）、总生存期（OS）更长［ 5 ］ 。总的来说，在TNBC患者新辅助治疗中使用阿替利珠单抗可以显著提高pCR率。KEYNOTE-522研究表明帕博利珠单抗联合化疗（卡铂+紫杉醇序贯多柔比星/表柔比星+环磷酰胺）的pCR率达到64.8%，而对照组为51.2%（95%CI：5.4~21.8，P 1 cm residual invasive cancer or positive lymph nodes ( > pN1mic) after neoadjuvant chemotherapy [J]. 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中华医学杂志. 标准与规范丨三阴性乳腺癌免疫检查点抑制剂临床应用专家共识（2025版）[S/OL]. 2025.