中国三阴性乳腺癌研究登全球最大讲坛
圣安东尼奥乳腺癌论坛（SABCS）由美国癌症研究学会、德克萨斯大学圣安东尼奥医学中心、休斯敦贝勒医学院联合主办，自1977年以来，已经成为全球规模最大的乳腺癌年度学术会议。其中，由于三阴性乳腺癌的治疗难度较大、治疗方案较少，是该论坛近年来的最热门课题之一。对于早期三阴性乳腺癌术后患者，目前标准的辅助化疗方案包括多西他赛等紫杉类和表柔比星等蒽环类，如果同时加入氟尿嘧啶前体口服靶向化疗药物卡培他滨，可能提高疗效，不过既往研究数据主要来自欧美晚期患者，缺乏有说服力的中国早期患者研究数据。
美国中部时间2019年12月11日上午10:30（北京时间2019年12月12日上午00:30），复旦大学附属肿瘤医院（上海市肿瘤医院）李俊杰登上第42届圣安东尼奥乳腺癌论坛首场全体大会主题发言讲坛，面对来自世界各地上百个国家或地区的上万位乳腺癌工作者，代表该院余科达和邵志敏、哈尔滨医科大学附属第三医院（黑龙江省肿瘤医院）庞达、吉林省肿瘤医院王长青、重庆西南医院（陆军军医大学第一附属医院）姜军、甘肃省肿瘤医院杨碎胜、河北医科大学第四医院（河北省肿瘤医院）刘运江、浙江省第一医院（浙江大学医学院附属第一医院）傅佩芬、上海长海医院（海军军医大学第一附属医院）盛湲、汕头大学医学院附属肿瘤医院张国君、南昌市第三医院（江西乳腺专科医院）曹亚丽、中国福利会国际和平妇幼保健院（上海交通大学医学院附属国际和平妇幼保健院）何奇、河南省肿瘤医院（郑州大学附属肿瘤医院）崔树德、西安交通大学第二附属医院（西北医院）王西京、重庆医科大学附属第一医院任国胜、山西省肿瘤医院（山西医科大学附属肿瘤医院）李炘正、苏州市立医院（南京医科大学附属苏州医院）俞士尤、广东省中医院（广州中医药大学第二附属医院）刘鹏熙、江苏省肿瘤医院（南京医科大学附属肿瘤医院）唐金海、温州医科大学附属第一医院（浙江省立温州第一医院）王瓯晨、吉林大学第一医院范志民、苏州大学第二附属医院蒋国勤、天津医科大学附属肿瘤医院（天津市肿瘤医院）张瑾等学者，报告了中国乳腺癌临床研究协作组（CBCSG）第010号研究长达5年的随访结果，探讨了将卡培他滨加入中国早期三阴性乳腺癌患者术后标准辅助化疗方案的有效性和安全性。
ClinicalTrials.gov Identifier NCT01642771: Comparative Study on Two Post-operative Adjuvant Chemotherapy Regimens for Treating Triple-negative Breast Cancer (A Prospective, Randomized, Open, Multi-center Phase III Clinical Study Comparing Efficacy and Safety of Sequential T-FEC and TX-XEC as Post-operative Adjuvant Chemotherapy Options for the Treatment of Triple-negative Breast Cancer)
该全国多中心前瞻非盲随机对照三期临床研究于2012年6月～2013年11月从全国35家医院入组早期三阴性乳腺癌手术切除后女性患者585例，按1∶1的比例随机分入两组：
卡培他滨组297例：卡培他滨＋多西他赛3个周期 → 环磷酰胺＋表柔比星＋卡培他滨3个周期（TX-XEC）
对照组288例：多西他赛3个周期 → 环磷酰胺＋表柔比星＋氟尿嘧啶3个周期（T-FEC）
随机分组集中进行，未行分层。主要研究终点为5年无病生存。
结果，实际治疗患者561例：卡培他滨组288例、对照组273例。两组患者基本特征相似。
中位随访67个月，卡培他滨组与对照组相比：
5年无病生存比例显著较高（86.26%比80.23%）
发病或死亡风险低34%（风险比：0.66，95%置信区间：0.44～0.98，P=0.038）
5年总体生存比例相似（93.27%比90.55%）
死亡风险低33%（风险比：0.67，95%置信区间：0.37～1.22，P=0.19）
总体而言，38.89%的患者减少卡培他滨剂量，8.42%的患者报告3～4级手足综合征。
卡培他滨组与对照组相比，发生率最高的3～4级血液毒性反应：
中性粒细胞减少：45.79%比41.32%
中性粒细胞减少伴发热：16.5%比15.97%
药物安全数据符合卡培他滨已知安全特征，并且两组患者大致相似。
因此，该研究结果表明，标准的紫杉类＋蒽环类辅助化疗同时，口服卡培他滨可以显著提高中国早期三阴性乳腺癌术后患者的长期无病生存比例，而且未发生新的安全问题。
相关阅读
Cancer Res. 2020;80(4 Suppl):GS1-08.
Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple-negative breast cancer (CBCSG010): An open-label, randomised, multicentre, phase 3 trial.
Junjie Li, Keda Yu, Da Pang, Changqin Wang, Jun Jiang, Suisheng Yang, Yunjiang Liu, Peifen Fu, Yuan Sheng, Guojun Zhang, Yali Cao, Qi He, Shude Cui, Xijing Wang, Guosheng Ren, Xinzheng Li, Shiyou Yu, Pengxi Liu, Jinhai Tang, Ouchen Wang, Zhimin Fan, Guoqin Jiang, Jin Zhang, Zhimin Shao; Chinese Breast Cancer Study Group (CBCSG).
Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China; The Third Affiliated Hospital of Harbin Medical University, Harbin, China; Jinlin Cancer Hospital & Institute, Changchun, China; South West Hospital, Chongqing, China; Gansu Cancer Hospital, Lanzhou, China; The Fourth Clinical Medical College of Hebei Medical University, Shijiazhuang, China; Zhejiang First Hospital, Hangzhou, China; Changhai Hospital of Shanghai, Shanghai, China; Cancer Hospital of Shantou Medical College, Shantou, China; The Third Affiliated Hospital of Nanchang University, Nanchang, China; The International Peace Maternity & Child Health Hospital of China Welfare Institute, Shanghai, China; Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China; The Second Affiliated Hospital of Medical College of Xi'An Jiaotong University, Xi'an, China; The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Shanxi Cancer Hospital, Taiyuan, China; Eastern Hospital of Suzhou Municipal Hospital, Suzhou, China; Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China; Jiangsu Cancer Hospital, Suzhou, Jiangsu, China; The First Hospital of Wenzhou Medical College, Wenzhou, China; The First Hospital of Jilin University, Changchun, China; The Second Affiliated Hospital of Soochow University, Suzhou, China; Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
BACKGROUND: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) comprises a taxane and an anthracycline. Concomitant capecitabine may add efficacy benefits, but robust data are lacking. The efficacy and safety of capecitabine integration into the TNBC adjuvant treatment regimen was evaluated.
METHODS: This was a randomised, open-label, phase 3 trial conducted in China (ClinicalTrials.gov identification NCT01642771). Post-resection, eligible female patients with early TNBC were randomly assigned (1:1) to either capecitabine treatment (3 cycles of capecitabine and docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine [TX-XEC]), or control treatment (3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil [T-FEC]). Randomisation was centralised without stratification. The primary endpoint was 5-year disease-free survival (DFS).
FINDINGS: Between June 2012 and November 2013, 585 patients were randomized to treatment (capecitabine, n=297; control, n=288), of whom 561 were treated per protocol (n=288 and n=273, respectively). Median follow-up was 67 months. The 5-year DFS rate was longer with capecitabine than with control treatment (86.26% vs. 80.23%, hazard ratio 0.66, 95% confidence intervals 0.44-0.98; p=0.038). The 5-year overall survival rates were similar (93.27% vs. 90.55%, respectively). Overall, 38.89% patients had capecitabine dose reductions and 8.42% reported grade 3/4 hand-foot syndrome. The most common grade 3/4 hematologic toxicities were neutropenia (capecitabine 136 [45.79%] patients vs. control 119 [41.32%] patients) and febrile neutropenia (49 [16.5%] vs. 46 [15.97%] patients). Safety data were in line with the known capecitabine safety profile and generally comparable between arms.
INTERPRETATION: Capecitabine, when administered concomitantly with standard adjuvant taxane/anthracycline chemotherapy, significantly improved DFS rates in TNBC, with no new safety concerns.
December 11, 2019, 10:30 AM - 10:45 AM