Randomized trial of fixed dose capecitabine compared to standard dose capecitabine in metastatic breast cancer: The X-7/7 trial.

1007 Background: In metastatic breast cancer (MBC), oral capecitabine prescribed at the FDA approved dose of 1250 mg/m 2 twice daily, 14 days on followed by 7 days off, is associated with poor tolerance and high discontinuation rates. Mathematical models suggest a fixed dose, dose dense (7 days on, 7 days off) schedule may be optimal for capecitabine efficacy. We conducted a randomized trial to compare the efficacy and tolerability of fixed-dose capecitabine, 1500 mg twice daily, 7 days on, 7 days off (FD) to the FDA approved dose and schedule (SD). Methods: Females with MBC and any prior lines of endocrine therapy or chemotherapy were included. HER-2 positive patients were allowed with concurrent trastuzumab. Patients were stratified by line of chemotherapy (first or subsequent), measurable disease, and ER status, and randomized 1:1 to either FD or SD. The primary endpoint was 3-month progression free survival (PFS). Additional endpoints included PFS and overall survival (OS). Capecitabine related toxicities were solicited and graded at each visit. Results: Between October 2015 and April 2021, 153 patients were enrolled (N=80 FD, N=73 SD) . 78% were hormone receptor positive/HER-2 negative, 11% each were HER-2 positive and triple negative. The 3-month PFS was 76% in the FD arm and 76% in the SD arm (HR=1.01; 95% CI, 0.52 to 1.94; p=0.99). Landmark analysis of PFS at 12, 24 and 36 months is reported. Non-proportional hazards were detected, so restricted mean survival time (RMST) was used to report estimates of effect. PFS (restricted mean) at 36 months was 13.9 months in the FD arm versus 14.6 months in the SD arm (hazard ratio for progression or death, 1.31; 95% CI, 0.56 to 1.15; p=0.24). OS (restricted mean) at 36 months was 21.2 months in the FD arm versus 19.6 months in the SD arm (hazard ratio for death, 0.80; 95% CI, 0.55 to 1.81; p=0.27). Toxicity related treatment discontinuation occurred in 21 patients (28.8%) in the SD arm compared to 6 patients (7.5%) in the FD arm (p<0.0006). Grade 2-4 toxicities (Table) occurred more frequently in patients receiving SD capecitabine (49.3%) as compared to FD capecitabine (25.0%) (p=0.0018). Conclusions: Fixed dose capecitabine (1500 mg twice daily) on a 7/7 schedule has less toxicity and similar survival when compared to standard BSA-based dosing on a 14/7 schedule in MBC. Clinical trial information: NCT02595320 . [Table: see text]