Li Junjie, Yu Keda, Pang Da, Wang Changqin, Jiang Jun, Yang Suisheng, Liu Yunjiang, Fu Peifen, Sheng Yuan, Zhang Guojun, Cao Yali, He Qi, Cui Shude, Wang Xijing, Ren Guosheng, Li Xinzheng, Yu Shiyou, Liu Pengxi, Qu Xiang, Tang Jinhai, Wang Ouchen, Fan Zhimin, Jiang Guoqin, Zhang Jin, Wang Jiandong, Zhang Hongwei, Wang Shui, Zhang Jianguo, Jin Feng, Rao Nanyan, Ma Binlin, He Pingqing, Xu Binghe, Zhuang Zhigang, Wang Jianfeng, Sun Qiang, Guo Xiaofeng, Mo Miao, Shao Zhimin
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Key Laboratory of Breast Cancer in Shanghai, Shanghai, People's Republic of China.
J Clin Oncol. 2020 Jun 1;38(16):1774-1784. doi: 10.1200/JCO.19.02474. Epub 2020 Apr 10.
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.
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).
Between June 2012 and December 2013, 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% 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; = .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.
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.
三阴性乳腺癌（TNBC）的标准辅助化疗包括紫杉烷和蒽环类药物。联合使用卡培他滨可能有益，但缺乏有力数据支持。本研究评估了在TNBC辅助治疗方案中添加卡培他滨的疗效和安全性。
本随机、开放标签的III期试验在中国进行。确诊手术后的符合条件的早期TNBC女性患者被随机分配（1:1）至卡培他滨组（3个周期的卡培他滨和多西他赛，随后是3个周期的卡培他滨、表柔比星和环磷酰胺）或对照组（3个周期的多西他赛，随后是3个周期的氟尿嘧啶、表柔比星和环磷酰胺）。随机分组是集中进行的，未进行分层。主要终点是无病生存期（DFS）。
2012年6月至2013年12月期间，636例TNBC患者接受筛查，585例被随机分配接受治疗（对照组288例；卡培他滨组297例）。中位随访时间为67个月。卡培他滨组的5年DFS率高于对照组（86.3%对80.4%；风险比，0.66；95%CI，0.44至0.99；P = 0.044）。5年总生存率在数值上更高，但未显著改善（卡培他滨组，93.3%；对照组，90.7%）。总体而言，39.1%的患者减少了卡培他滨剂量，8.4%的患者报告有≥3级手足综合征。最常见的≥3级血液学毒性是中性粒细胞减少（卡培他滨组，136例[45.8%]；对照组，118例[41.0%]）和发热性中性粒细胞减少（卡培他滨组，50例[16.8%]；对照组，46例[16.0%]）。安全性数据与已知的卡培他滨安全性概况相似，两组之间总体相当。
在3个周期的多西他赛后添加卡培他滨，随后3个周期使用含卡培他滨而非氟尿嘧啶的三联蒽环类药物组合，可显著改善TNBC的DFS，且无新的安全性问题。
