对于早期三阴性乳腺癌患者，目前标准的术后辅助化疗方案包括多西他赛等紫杉类药物和表柔比星等蒽环类药物，如果同时加入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。
4月10日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表复旦大学附属肿瘤医院李俊杰、余科达、莫淼、邵志敏、哈尔滨医科大学附属第三医院庞达、吉林省肿瘤医院王长青、重庆西南医院姜军、甘肃省肿瘤医院杨碎胜、河北医科大学第四医院刘运江、浙江大学医学院附属第一医院傅佩芬、上海长海医院盛湲、汕头大学医学院附属肿瘤医院张国君、南昌市第三医院曹亚丽、中国福利会国际和平妇幼保健院何奇、河南省肿瘤医院崔树德、西安交通大学第二附属医院王西京、重庆医科大学附属第一医院任国胜、山西省肿瘤医院李炘正、苏州市立医院俞士尤、广东省中医院刘鹏熙、首都医科大学附属北京友谊医院屈翔、江苏省肿瘤医院唐金海、温州医科大学附属第一医院王瓯晨、吉林大学第一医院范志民、苏州大学第二附属医院蒋国勤、天津医科大学肿瘤医院张瑾、解放军总医院王建东、复旦大学附属中山医院张宏伟、江苏省人民医院王水、哈尔滨医科大学附属第二医院张建国、中国医科大学附属第一医院金锋、中山大学孙逸仙纪念医院饶南燕、新疆医科大学附属肿瘤医院马斌林、上海市第六人民医院何萍青、中国医学科学院肿瘤医院徐兵河、上海市第一妇婴保健院庄志刚、上海市第一人民医院王建丰、北京协和医院孙强等学者的中国乳腺癌临床研究协作组CBCSG010研究5年随访结果，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。
CBCSG010 (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 (NCT01642771)
该全国多中心前瞻非盲随机对照三期临床研究于6月～12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的比例随机分为两组：
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）
标准化疗组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。主要研究终点为无病生存，次要研究终点包括无复发生存、无远处病变生存、总生存。
结果，中位随访67个月，卡培他滨组与标准化疗组相比：
无病生存比例较高（86.26%比80.23%）
发病死亡风险低34%（风险比：0.66，95%置信区间：0.44～0.99，P=0.044）
无复发生存比例较高（89.5%比83.1%）
复发死亡风险低41%（风险比：0.59，95%置信区间：0.38～0.93，P=0.02）
无远处病变生存比例较高（89.8%比84.2%）
远处病变死亡风险低37%（风险比：0.63，95%置信区间：0.39～1.0，P=0.048）
总生存比例相似（93.3%比90.7%）
总死亡风险低33%（风险比：0.67，95%置信区间：0.37～1.22，P=0.19）
亚组分析表明，无论是否绝经、淋巴结是否转移、肿瘤大小、TNM分期高低、分级高低、增殖指数Ki-67高低，卡培他滨组与标准化疗组相比，无病生存比例都较高。
总体而言，38.89%的患者卡培他滨减量，8.42%的患者报告≥3级手足综合征。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。卡培他滨组与标准化疗组相比，发生率最高的≥3级血液毒性反应：
中性粒细胞减少：45.8%比41.0%
中性粒细胞减少伴发热：16.8%比16.0%
因此，该研究结果表明，对于早期三阴性乳腺癌术后患者，紫杉类＋蒽环类标准辅助化疗方案±口服卡培他滨相比，5年无病生存比例显着较高，而且未发生新的安全问题。
相关链接
中国三阴性乳腺癌研究登全球最大讲坛
三阴乳腺癌卡培他滨辅助化疗荟萃分析
卡培他滨对早期三阴乳腺癌化疗的作用
早期乳腺癌老年患者卡培他滨十年结局
早期乳腺癌术后卡培他滨辅助治疗之争
乳腺癌辅助化疗：加速表柔比星无益，口服卡培他滨取代静脉三药有益
乳腺癌术前化疗失败后的卡培他滨辅助疗法安全有效
J Clin Oncol. Apr 10. [Epub ahead of print]
Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial.
Junjie Li, Keda Yu, Da Pang, Changqin Wang, Jun Jiang, Suisheng Yang, Yunjiang Liu, Peifen Fu, Yuan Shen, Guojun Zhang, Yali Cao, Qi He, Shude Cui, Xijing Wang, Guosheng Ren, Xinzheng Li, Shiyou Yu, Pengxi Liu, Xiang Qu, Jinhai Tang, Ouchen Wang, Zhimin Fan, Guoqin Jiang, Jin Zhang, Jiandong Wang, Hongwei Zhang, Shui Wang, Jianguo Zhang, Feng Jin, Nanyan Rao, Binlin Ma, Pingqing He, Binghe Xu, Zhigang Zhuang, Jianfeng Wang, Qiang Sun, Xiaofeng Guo, Miao Mo, Zhimin Shao; CBCSG Study Group.
Fudan University Shanghai Cancer Center, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China; The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Jilin Cancer Hospital and Institute, Changchun, Jilin, China; Southwest Hospital, Chongqing, Chongqing, China; Gansu Cancer Hospital, Lanzhou, Gansu, China; The Fourth Clinical Medical College of Hebei Medical University, Shijiazhuang, Hebei, China; The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Changhai Hospital of Shanghai, Shanghai, China; Cancer Hospital of Shantou Medical College, Shantou, Guangdong, China; The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; The International Peace Maternity and Child Health Hospital of China, Welfare Institute, Shanghai, China; Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China; Medical College, The Second Affiliated Hospital of Xi"An Jiaotong University, Xi"an, Shanxi, China; The First Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing, China; Shanxi Cancer Hospital, Taiyuan, Shanxi, China; Eastern Hospital of Suzhou Municipal Hospital, Suzhou, Jiangsu, China; Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China; Beijing Friendship Hospital, Capital Medical University, Beijing, China; Jiangsu Cancer Hospital, Suzhou, Jiangsu, China; The First Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China; The First Hospital of Jilin University, Changchun, Jilin, China; The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; The General Hospital of the People"s Liberation Army, Beijing, China; Zhongshan Hospital, Fudan University, Shanghai, China; Jiangsu Province Hospital, Suzhou, Jiangsu, China; The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; The First Hospital of China Medical University, Shenyang, Liaoning, China; The Second Affiliated Hospital of Zhongshan University, Guangzhou, Guangdong, China; Xinjiang Cancer Hospital, Wulumuqi, Xinjiang, China; Shanghai Sixth People"s Hospital, Shanghai, China; Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China; Shanghai First Maternity and Infant Hospital Corporation, Shanghai, China; Shanghai General Hospital, Shanghai, China; Peking Union Medical College Hospital, Beijing, China; Continuing Education and Technology Services Department, Chinese Anti-Cancer Association, Tianjin, China.
PURPOSE: Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated.
PATIENTS AND METHODS: This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS).
RESULTS: Between June and December , 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = 0.044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms.
CONCLUSION: Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.
DOI: 10.1200/JCO.19.02474
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