Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial

The randomized phase III JO21095 trial compared the efficacy and safety of low-dose capecitabine plus docetaxel combination therapy (XT) versus single-agent administration of docetaxel in anthracycline-pretreated HER2-negative metastatic breast cancer. Patients were randomized to either low-dose XT (capecitabine 825 mg/m(2) twice daily, days 1-14; docetaxel 60 mg/m(2), day 1 every 3 weeks) or docetaxel (70 mg/m(2), day 1 every 3 weeks). The primary objective was to demonstrate superior progression-free survival (PFS) with low-dose XT versus single-agent docetaxel. Overall survival (OS) and safety were secondary endpoints. In total, 162 patients were treated. Median PFS was 10.5 months with low-dose XT and 9.8 months with single-agent docetaxel (hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.40-0.97]; p = 0.03). The OS HR was 0.89 (95% CI 0.52-1.53; p = 0.68). Grade >= 3 treatment-related toxicities occurred in 74% of XT-treated patients and 76% of docetaxel-treated patients. The main differences in grade >= 3 treatment-related toxicities were hand-foot syndrome (7.3% of XT-treated patients vs 0% receiving docetaxel), fatigue/malaise (2.4 vs 10.0%), and peripheral edema (1.2 vs 7.5%). Dose modifications were required in 100% of low-dose XT and 49% of docetaxel patients. Toxicity-related treatment discontinuations occurred in 18 and 33%, respectively. The improved PFS with low-dose XT versus docetaxel alone is consistent with higher-dose XT phase III experience, but the safety profile was more favorable and manageable.