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.

Trial registration: ClinicalTrials.gov NCT01642771.

FIG 1.

CONSORT diagram of patient disposition. mITT, modified intention to treat; PPS, per-protocol set; T-FEC, 3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide; XT-XEC, 3 cycles of capecitabine plus docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide.

FIG 2.

Kaplan-Meier estimates of 5-year survival (modified intention-to-treat population; n = 585). (A) Disease-free survival (DFS), (B) recurrence-free survival (RFS), (C) distant DFS (DDFS), and (D) overall survival (OS). HR, hazard ratio; T-FEC, 3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide; XT-XEC, 3 cycles of capecitabine plus docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide.

FIG 3.

Results of exploratory subgroup analyses for disease-free survival. A forest plot shows the hazard ratios (HRs) and 95% CIs (horizontal lines) according to menstrual status, tumor size, nodal status, grade, and protein encoded by the MKI67 gene (Ki-67) status. Data are from the log-rank test. Data are presented as number of patients with events of total number of patients. T-FEC, 3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide; XT-XEC, 3 cycles of capecitabine plus docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide.

FIG A1.

Kaplan-Meier estimates of 5-year disease-free survival (DFS) per-protocol set population (n = 564). HR, hazard ratio; T-FEC, 3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide; XT-XEC, 3 cycles of capecitabine plus docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide.