Randomized phase II non-inferiority study (NO16853) of two different doses of capecitabine in combination with docetaxel for locally advanced/metastatic breast cancer.

Background: This phase II study investigated whether a lower-than-approved dose of capecitabine, plus docetaxel (XT), would improve tolerability versus standard-dose XT without compromising efficacy.

Patients And Methods: Women aged ≥18 years with locally advanced/metastatic breast cancer resistant to anthracycline-based chemotherapy in the (neo)adjuvant, first- or second-line metastatic setting were eligible. Patients were randomly assigned to receive standard-dose XT (capecitabine 1250 mg/m(2) twice daily, days 1-14; docetaxel 75 mg/m(2), day 1 every 3 weeks) or low-dose XT (capecitabine 825 mg/m(2) twice daily, days 1-14; docetaxel as above). The primary objective was to demonstrate non-inferiority of low-dose to standard-dose XT in terms of progression-free survival (PFS).

Results: 470 patients were randomly allocated in a 1 : 1 ratio to standard-dose or low-dose XT. Median PFS was 7.9 versus 5.8 months [hazard ratio 1.16, 95% confidence interval (CI) 0.95-1.43] in the standard-dose and low-dose arms, respectively. The upper limit of the 95% CI was above the predefined non-inferiority margin (1.35, P = 0.078). Secondary efficacy end points were consistent with PFS. The frequency and severity of adverse events was similar in both treatment arms.

Conclusions: Non-inferiority of low-dose to standard-dose XT in terms of PFS was not demonstrated; this may be due to regional subgroup effects.