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投稿时间：2022-02-09 网络发布日期：2022-09-20
投稿时间：2022-02-09 网络发布日期：2022-09-20
中文摘要: 目的 解析三阴性乳腺癌（TNBC）含免疫检查点抑制剂治疗方案的Ⅲ期临床研究。方法 检索美国临床试验注册中心（ClinicalTrials.gov）有关TNBC含免疫检查点抑制剂治疗方案的Ⅲ期临床研究，时间截至2021年12月。结果 共检索相关Ⅲ期临床研究17项，其中程序性细胞死亡受体1（PD-1）相关研究7项（帕博利珠单抗5项+卡瑞利珠单抗2项），程序性细胞死亡受体-配体1（PD-L1）相关研究10项（阿替利珠单抗9项+Avelumab 1项）。单臂研究1项，随机对照研究16项。17项研究中仅2项研究NCT02425891(IMpassion130)和NCT02555657(KEYNOTE-119)已全部完成，6项研究仍在招募中，另外9项研究尚未完成，但不再招募患者。截至目前，共有6项研究已公布初步或更新的研究结果。IMpassion130研究结果显示，一线阿替利珠单抗联合紫杉醇（白蛋白结合型）治疗能够显著改善全部TNBC患者的无进展生存（PFS）和PD-L1阳性患者的总生存（OS）。同样，KEYNOTE-355研究发现一线帕博利珠单抗联合化疗对联合阳性评分（CPS）≥10患者的PFS有显著改善。但KEYNOTE-119和IMpassion131研究分别揭示二线或三线单药帕博利珠单抗及一线阿替利珠单抗联合普通紫杉醇未能改善患者的PFS和或OS。IMpassion031和KEYNOTE-522研究表明在早期 TNBC中，阿替利珠单抗或帕博利珠单抗联合紫杉类和蒽环类化疗的新辅助治疗能够显著提高患者的病理完全缓解（pCR）且总体安全性较好。结论 含免疫检查点抑制剂联合治疗方案在早期、局部晚期和/或转移TNBC中均显示出一定的临床获益，但最佳联合方案和目标人群的选择仍需进一步研究证实。
Abstract:Objective To analyze the phase Ⅲ clinical study of immune checkpoint inhibitor in triple-negative breast cancer (TNBC). Methods The related data from ClinicalTrials.gov until December 2021 was searched. Results A total of 17 relevant studies were collected, including 7 PD-1-related studies (Pembrolizumab×5+Camrelizumab×2) and 10 PD-L1-related studies (Atezolizumab×9+Avelumab×1), including 1 single-arm study and 16 randomized controlled studies. Of which only 2 studies ［NCT02425891 (IMpassion130) and NCT02555657 (KEYNOTE-119)］ had been completed, 6 studies were still recruiting, and the other 9 studies had not been completed but no longer recruiting. So far, a total of 6 studies had preliminary or updated results. IMpassion130 showed that first-line Atezolizumab combined with Nab-Paclitaxel significantly improve PFS in all TNBC patients and OS in PD-L1 positive patients. Similarly results were observed in KEYNOTE-355. Different from the above two studies, KEYNOTE-119 and IMpassion131 revealed that both second-line or third-line single-agent Pembrolizumab and first-line Atezolizumab combined with Paclitaxel did not improve PFS and/or OS in patients. IMpassion031 and KEYNOTE-522 showed that neoadjuvant therapy with Atezolizumab or Pembrolizumab combined with Taxane and Anthracycline significantly improve pCR(pathological complete response) in early-stage TNBC. Compared with placebo group, immunotherapy in combination with chemotherapy was safety. Conclusion Combination of immune checkpoint inhibitors has certain clinical significance in early, locally advanced and/or metastatic TNBC, but the choice of optimal combination regimen and population still needs to be further confirmed by more large-sample studies in the future.
keywords: Triple negative breast cancer Immune checkpoint inhibitor Phase Ⅲ clinical study PD-1 PD-L1 Atezolizumab Pembrolizumab Camrelizumab
文章编号： 中图分类号：R737.9 文献标志码：A
基金项目:江苏省社会发展重点项目—临床前沿技术（BE2021741）
引用文本：
李萍,朱程君,孙月,等.三阴性乳腺癌含免疫检查点抑制剂治疗方案的Ⅲ期临床研究解析[J].中国临床研究,2022,35(9):1205-1210.
李萍,朱程君,孙月,等.三阴性乳腺癌含免疫检查点抑制剂治疗方案的Ⅲ期临床研究解析[J].中国临床研究,2022,35(9):1205-1210.