Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial

Abstract

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 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% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .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.

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

“…A total of 3842 TNBC patients were included in this meta-analysis. In two of the trials, the entire cohort of patients had TNBC [ 19 , 21 ], while in the other seven trials TNBC patients were one of the subgroups. The main research features are shown in Table 1 .…”

“…There were five [ 14 , 17 – 19 , 21 ] and four [ 15 , 16 , 20 , 22 ] studies involving the addition or replacement of capecitabine to neoadjuvant or adjuvant chemotherapy, respectively. From the available data of TNBC, there were 1373 capecitabine combined and 1356 capecitabine-free cases in the group with the addition of capecitabine, and 384 capecitabine combined and 357 capecitabine-free cases in the group with the replacement of capecitabine.…”

“…There were seven [ 14 – 19 , 21 , 22 ] and one [ 20 ] studies that used capecitabine as adjuvant and neoadjuvant chemotherapy, respectively, and one study that used capecitabine as both neoadjuvant and adjuvant chemotherapy [ 19 ]. From the available data of TNBC, there were 1757 cases of adjuvant chemotherapy with capecitabine and 1713 cases of adjuvant chemotherapy without capecitabine, along with 448 cases of neoadjuvant chemotherapy with capecitabine and 428 cases of neoadjuvant chemotherapy without capecitabine.…”

“…Two studies (CIBOMA 2004/01, CBCSG-010) [ 19 , 21 ] reported that there is a relationship between lymph node status of TNBC patients and neoadjuvant or adjuvant chemotherapy including capecitabine. There were 295 lymph node-positive cases and 440 lymph node-negative cases in the capecitabine group, along with 285 lymph node-positive cases and 427 lymph node-negative cases in the capecitabine-free group.…”

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis

“…Based on the tumor burden, optimal treatments, namely breast-conserving surgery, radiotherapy, chemotherapy, and endocrine therapy, are individually designed for breast cancer patients [ 6 ]. For TNBC patients, anthracyclines and taxanes are preferred in the initial treatment, and neoadjuvant therapy has been recognized as a standard strategy [ 9 – 12 ]. Unfortunately, neither endocrine therapy nor trastuzumab treatment is effective for TNBC.…”