三阴性乳腺癌术后卡铂＋紫杉化疗有效
蒽环类＋环磷酰胺→紫杉类是乳腺癌化疗标准方案之一，可是不良反应较大，患者的依从性和耐受性较差。铂类对于三阴性乳腺癌早期患者术前新辅助治疗和晚期患者转移后治疗具有重要作用，患者的依从性和耐受性相对较好。不过，铂类对于三阴性乳腺癌早期患者术后辅助治疗的作用尚不明确。
2020年5月11日，施普林格自然旗下《乳腺癌研究与治疗》在线发表中国医学科学院肿瘤医院杜丰、朱安婕、王佳玉、蔡锐刚、马飞、樊英、李青、张频、袁芃、徐兵河、北京大学肿瘤医院杜丰、山东省肿瘤医院王永胜、首都医科大学附属北京潞河医院李明、黑山大学临床中心弗拉基米尔·托多罗维奇的研究报告，对早期三阴性乳腺癌患者术后卡铂＋紫杉类辅助化疗的非劣效性进行了探讨。
该多中心非劣效随机对照二期临床研究于2009年6月1日～2015年10月31日从中国医学科学院肿瘤医院、山东省肿瘤医院、首都医科大学附属北京潞河医院入组经组织学确认为三阴性乳腺癌尚未化疗的初次手术后患者308例，按1∶1的比例随机分为两组：
TP组154例：6个周期紫杉类＋卡铂化疗（每3周第1天多西他赛75mg/m²或紫杉醇175mg/m²＋卡铂AUC=5）
EC→T组154例：4个周期表柔比星＋环磷酰胺→4个周期紫杉类化疗（每3周第1天表柔比星90mg/m²＋环磷酰胺600mg/m²→每3周第1天多西他赛75mg/m²或紫杉醇175mg/m²）
主要终点为5年无病生存，并对乳腺癌遗传基因突变和细胞程序性死亡蛋白配体PD-L1表达的预后和预测价值进行评估。
结果，中位随访66.9个月时，EC→T组与TP组相比：
5年无病生存比例相似：85.8%比84.4%（对数秩P=0.712，非劣效P=0.034）
5年总体生存比例相似：94.4%比93.5%（对数秩P=0.770）
TP组与EC→T组相比，依从性较好，3～4级中性粒细胞减少、3～4级脱发发生比例显著较低，1～4级血小板减少发生比例较高。
表达与未表达PD-L1的肿瘤患者相比，无病生存和总体生存的比例显著较高。
因此，该研究结果表明，对于无法耐受蒽环类高强度化疗的早期三阴性乳腺癌术后患者，卡铂＋紫杉类有望成为安全有效的辅助化疗替代方案之一，故有必要开展三期临床研究进行验证。
Breast Cancer Res Treat. 2020 May 11. [Epub ahead of print]
Carboplatin plus taxanes are non-inferior to epirubicin plus cyclophosphamide followed by taxanes as adjuvant chemotherapy for early triple-negative breast cancer.
Feng Du, Wenmiao Wang, Yongsheng Wang, Ming Li, Anjie Zhu, Jiayu Wang, Ruigang Cai, Fei Ma, Ying Fan, Qing Li, Pin Zhang, Vladimir Todorovic, Peng Yuan, Binghe Xu.
National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Peking University Cancer Hospital and Institute, Beijing, China; Shandong Cancer Hospital/Institute, Jinan, Shandong, China; Beijing Luhe Hospital, Capital Medical University, Beijing, China; Clinical Centre of Montenegro, Podgorica, Montenegro.
PURPOSE: Platinum plays an important role in the treatment of triple-negative breast cancer (TNBC) in neoadjuvant and metastatic settings. However, its role in an adjuvant setting remains unclear.
METHODS: In this non-inferior randomized phase 2 trial, we randomly assigned 308 chemotherapy-naive patients with histologically confirmed TNBC after primary surgery to receive either six cycles of TP (docetaxel: 75 mg/m2 or paclitaxel 175 mg/m2 d1; carboplatin AUC=5, day 1), or four cycles of EC (epirubicin: 90 mg/m2; cyclophosphamide: 600 mg/m2, day 1) followed by four cycles of T (docetaxel: 75 mg/m2 or paclitaxel 175 mg/m2, day 1). The primary end point was the disease-free survival (DFS) rate at 5 years. Both regimens were repeated every 3 weeks. The prognostic and predictive value of germline breast cancer gene mutations and programmed death ligand-1 (PD-L1) expression was evaluated.
RESULTS: At a median follow-up of 66.9 months, the 5-year DFS rate was 85.8% in the EC-T arm, and 84.4% in the TP arm (p non-inferiority=0.034, p log-rank=0.712). The 5-year overall survival (OS) rate was 94.4% in the EC-T arm and 93.5% in the TP arm (p=0.770). Patients in the TP arm showed better compliance and experienced significantly lower frequencies of G3/4 neutrocytopenia and G3/4 alopecia, but higher rates of G1-4 thrombocytopenia than those in the EC-T arm. Patients with PD-L1 expressing tumors showed significantly improved DFS and OS.
CONCLUSIONS: This study indicates that carboplatin plus taxanes could be a feasible adjuvant chemotherapy for patients with early TNBC who are cannot tolerate intensive chemotherapy with anthracycline.
KEYWORDS: Triple-negative breast cancer, Adjuvant chemotherapy, Platinum, BRCA mutation, PD-L1
DOI: 10.1007/s10549-020-05648-9