Randomized Trial of Fixed-Dose Capecitabine Compared With Standard-Dose Capecitabine in Metastatic Breast Cancer: X-7/7 Trial

PURPOSE In metastatic breast cancer (MBC), oral capecitabine prescribed at the US Food and Drug Administration (FDA)–approved dose of 1,250 mg/m 2 twice daily, 14 days on, 7 days off, is associated with poor tolerance. Mathematical models suggest that a fixed-dose (FD), dose-dense schedule may optimize efficacy. We conducted a randomized, open-label trial to compare the efficacy and tolerability of FD capecitabine, 1,500 mg twice daily, 7 days on, 7 days off (FD-7/7), with the FDA-approved dose and schedule (standard-dose SD-14/7). METHODS Females with MBC and any previous lines of therapy were included. Patients were randomly assigned 1:1 to either FD-7/7 or SD-14/7. The primary end point was 3-month progression-free survival (PFS). Capecitabine-related toxicities were graded at each visit. RESULTS Between October 2015 and April 2021, 153 patients were enrolled (n = 80 FD-7/7, n = 73 SD-14/7). The 3-month PFS was 63.1% (95% CI, 52.0 to 74.2) in the FD-7/7 arm and 67.2% (95% CI, 54.5 to 79.9) in the SD-14/7 arm. Restricted mean survival time was used to report estimates of effect. The PFS (restricted mean) at 33 months was 10.1 months (95% CI, 7.6 to 12.6) in the FD-7/7 arm compared with 9.1 months (95% CI, 6.6 to 11.7) in the SD-14/7 arm. The overall survival (restricted mean) at 80 months was 30.6 months (95% CI, 23.6 to 37.6) in the FD-7/7 arm versus 24.5 months (95% CI, 18 to 31.1) in the SD-14/7 arm. Toxicity-related treatment discontinuation occurred in 24 patients (32.9%) in the SD-14/7 arm compared with seven patients (8.8%) in the FD-7/7 arm ( P = .0002). Grade 2 to 4 toxicities occurred in 79.5% in the SD-14/7 arm compared with 37.5% in the FD-7/7 arm ( P < .0001). CONCLUSION In MBC, FD capecitabine 1,500 mg twice daily on a 7/7 schedule has less toxicity and similar efficacy when compared with body surface area-based dosing on a 14/7 schedule.