Concurrent use of capecitabine with radiation therapy and survival in breast cancer (BC) after neoadjuvant chemotherapy.

Abstract

e12117 Background: Capecitabine has been studied as a radiosensitizer in rectal cancer, but its role in BC is unclear. Our study seeks to examine the association of concurrent capecitabine/radiation therapy (RT) on survival in women with BC and residual disease after neoadjuvant chemotherapy (NAC). Methods: In a retrospective study of women with stage I-III BC who received Adriamycin/Taxane-based NAC from 2010-2016, we identified 21 women administered concurrent capecitabine/RT. To assess differences in survival, we selected a clinical control cohort (n = 64) based on criteria used to select patients for capecitabine/RT including pathological stage II/III disease and non-HER2+ tumor subtype. We also created a matched cohort (2:1), matching on tumor subtype, pathological stage, and age ( < 50 or 50+ years). Differences in progression-free survival (PFS), using STEEP criteria, and overall survival (OS), using all-cause mortality, between those who received capecitabine/RT and controls were assessed. Results: Of the 21 women who received capecitabine/RT, the majority were 50+ years (n = 12), pathological stage III (n = 15), and hormone receptor positive/HER2 negative BC (n = 20). Compared with clinical controls, women who received capecitabine/RT had larger disease (p = 0.041) and a higher pathological stage (p = 0.067), but there were no other differences. In those receiving capecitabine/RT, there were 9 recurrences (3 local, 6 distant) compared with 14 recurrences (4 local, 10 distant) in the clinical controls and 10 recurrences (all distant) in the matched controls. In multivariate models, capecitabine/RT was associated with worse PFS (HR 3.04 95% CI 1.24-7.43 p = 0.015) and OS (HR 4.29 95% CI 1.45- 12.6 p = 0.008), after adjusting for clinical size and pathologic stage. In the 2:1 matched cohort, capecitabine/RT was also associated with worse PFS (HR 2.96 95% CI 1.20-7.29 p = 0.018) and OS (HR 5.61 95% CI 1.76-17.9 p = 0.004). Conclusions: Capecitabine/RT after NAC is associated with worse PFS and OS using two control populations, suggesting capecitabine/RT should be discouraged in BC.

Modulating the Radiation Response for Improved Outcomes in Breast Cancer

“…Many chemotherapy agents used for the treatment of breast cancer work by inhibiting the synthesis of DNA or its precursors, including fluorinated pyrimidine analogs such as gemcitabine and 5-fluorouracil or the purine nucleoside antimetabolite cordycepin. 5 Preclinical studies with gemcitabine showed efficacy as radiosensitizing strategy in both wild-type and p53 mutant MCF-7 cells 6 (although initial results from others were mixed), 7 and have led to clinical trials with gemcitabine 8 and capecitabine 9,10 (ClinicalTrials.gov identifier: NCT03958721) in combination with RT. These pivotal studies were some of the first to demonstrate the value of combination chemotherapy and RT in breast cancer, which has led to an increased interest in the potential use of other chemotherapeutic agents with concurrent RT.…”

Post-neoadjuvant treatment with capecitabine and trastuzumab emtansine in breast cancer patients—sequentially, or better simultaneously?

“…In a retrospective study including 317 patients who received doxorubicin and taxan-based neoadjuvant chemotherapy from 2004 to 2016, Liu et al identified 21 patients receiving adjuvant radiotherapy over 6-8 weeks and simultaneous capecitabine [12]. In all patients, the whole breast and also the lymphatic pathways were included into the radiation fields.…”