Abstract 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
Authors: 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 , Tang Jinhai , Wang Ouchen , Fan Zhimin , Jiang Guoqin , Zhang Jin , Shao Zhimin ,   Chinese Breast Cancer Study Group (CBCSG) 010
Published: March 2020

Abstract
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.
Table 1: Baseline patient demographics and clinical characteristics (PPS population; n=561)T-FEC (n=273)TX-XEC (n=288)pAge (years), mean ± SD48.30 ± 8.7649.07 ± 10.440·3501BSA (m2), mean ± SD1.60 ± 0.111.60 ± 0.110·4209Menstruation0·2946Premenopausal61·5757·09Postmenopausal38·4342·91Family History26·3726·830·9029Operation TypeBreast conserving21·8525·090·3683Mastectomy78·1574·91SLNB28·5226·130·5275Axillary dissection71·4873·87Node Stage0·5967N065·0665·97N123·7925·35N26·323·82N34·834·86T Stage0·2938T1a,b4·172·33T1c42·5041·25T250·4255·25T32·921·17Histology0·7190IDC89·6390·24ILC0·741·39Other9·638·36Grade0·2322I3·832·94II47·6640·76III48·5156·30Ki67 ≥30%+87·2185·770·6245LVI +14·8110·100·1363Surgery-to-chemo time (days), mean ± SD16·94 ± 7·7717·99 ± 9·240·1581Data are % except where specified.BSA=body surface area; IDC=invasive ductal carcinoma; ILC=invasive lobular carcinoma; LVI=lymphovascular invasion; PPS=per protocol set; SD=standard deviation;Table 2: Number of events (PPS population; n=561)T-FECTX-XEC(n=273)(n=288)Any event57 (20·88)41 (14·24)Second primary4 (1·47)5 (1·74)Contralateral breast5 (1·83)6 (2·08)Local recurrence18 (6·59)7 (2·43)Ipsilateral breast/Chest135Regional lymph nodes83Distant recurrence37 (13·55)29 (10·07)Liver37Lung1714Bone67Other2714Death26 (9·52)19 (6·60)
Citation Format: 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) 010. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple-negative breast cancer (cbcsg010): An open-label, randomised, multicentre, phase 3 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS1-08.