Retrospective evaluation of adjuvant capecitabine dosing patterns in triple negative breast cancer.
Authors: Lin Kun , Michaels Elena , Polley Eric , O'Donnell Peter H. , Howard Frederick Matthew , Conzen Suzanne D. , Hahn Olwen Mary , Fleming Gini F. , Nanda Rita , Chen Nan , Yang Heng 
Published: June 2023

e12515 Background: Patients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant chemotherapy have an increased risk of relapse. The CREATE-X trial demonstrated that adjuvant capecitabine was effective in both reducing recurrence and prolonging survival in this high-risk population. However, the recommended dose (2500 mg/m2 per day) is generally not well tolerated in US populations. The goal of this study is to analyze dosing patterns in an ethnically diverse patient population to better characterize tolerability and inform future dosing guidelines. Methods: We conducted a single-center, retrospective study including TNBC patients who were treated with adjuvant capecitabine. The primary endpoint was relative dose intensity (RDI) of capecitabine, defined as the dose received relative to the dose intended across eight cycles. Subgroup analyses were performed by age, race, BMI, and initial starting dose. Secondary endpoints included capecitabine-related side effects, disease-free survival (DFS), and overall survival (OS). A one-sample t-test was used to compare the average RDI to the CREATE-X trial estimate. A two-sample t-test was performed to evaluate for differences in RDI between subgroups. A proportional hazards model estimated the impact of capecitabine dose on DFS and OS. Results: 67 patients who completed adjuvant capecitabine at the University of Chicago between January 2017 and November 2022 were eligible. The mean age was 55 years (range 20-77). 46.3% of patients were of self-reported Black race, 44.8% were non-Hispanic Whites, and 9% were other races. The mean RDI across eight cycles of treatment was 60.2% (95% CI 55.4% -65.0%). When compared to the CREATE-X trial, the RDI in our population was significantly lower (60.2% vs. 78.7%, p<0.001). There was no statistically significant difference in average RDI across eight cycles for patients stratified by age, BMI, race, or initial starting dose ≥ 2000mg/m2. Patients younger than 65 years had a higher average RDI compared to those 65 years and older (62.2% vs. 51.8%, p= 0.094), however, this was not statistically significant. Lower RDI did not confer worse DFS or OS ( p=0.4 , p=0.9 ). The most frequently reported adverse events were hand-foot syndrome (73%), diarrhea (27%), and fatigue (22%), consistent with prior studies. Conclusions: These data demonstrate that a significant portion of patients have a lower tolerated dose of capecitabine in comparison to the recommended adjuvant dose. Acknowledging the limitations of our single-center, underpowered analysis, RDI was not significantly affected by age, race, BMI, or recommended starting dose. Younger patients did however appear to have a better tolerance than older patients. Regardless, a lower RDI was not associated with worse long-term outcomes. Additional studies are needed to further investigate optimal capecitabine dosing strategies in diverse populations.