The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

Abstract

Background The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety. Methods PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs). Results A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65–0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53–0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53–0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63–0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44–0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23–3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53–2.64, P < 0.001) and hand–foot syndrome (OR = 8.67, 95% CI 6.70–11.22, P < 0.001). Conclusion This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

The Clinical Value of Chemotherapy Combined With Capecitabine in Triple-Negative Breast Cancer—A Meta-Analysis

“…A fixed effects model was applied to calculate the combined HR and 95% CI as 0.80 (0.71–0.90), P = 0.0003, indicating a statistically significant difference between capecitabine group and capecitabine-free group ( Figure 2 ). This demonstrated that capecitabine could significantly improve DFS in TNBC patients when combined with chemotherapy, which was consistent with the conclusions of two recent meta-analyses about the role of capecitabine for TNBC treatment ( Li Y. et al, 2020 ; Huo et al, 2021 ).…”

“…For some patients with special baseline characteristics, the benefits of capecitabine may be more obvious according to more clinical data and more rigorous analysis. The positive efficacy of adding capecitabine might depend on patient’s race, age and different clinical characteristics of patients ( Zhang et al, 2016 ; Li Y. et al, 2020 ; Huo et al, 2021 ).…”

“…Compared to other meta-analysis, we included more data and performed other subgroup analysis including the effect of capecitabine and cyclophosphamide in combination and the influence of capecitabine dose on adjuvant chemotherapy ( Zhang et al, 2016 ; Natori et al, 2017 ; Li Y. et al, 2020 ; Huo et al, 2021 ). The meta-analysis by Yan Li et al focused on the role of adjuvant capecitabine in standard chemotherapy, the influence of region and treatment period on the effect of capecitabine were analyzed in the subgroup.…”

“…At the same time, some analyses showed that the addition of capecitabine couldn't affect DFS but improve OS (Natori et al, 2017). Two meta-analyses focused on the role of capecitabine in the treatment of TNBC, the results confirmed that the addition of capecitabine could improve DFS and OS in TNBC patients (Li Y. et al, 2020;Huo et al, 2021). However, these meta-analyses were short of the latest updates of relevant clinical trials, and did not show further subgroup analysis such as the effect of capecitabine dose or combination with other chemotherapeutic drugs.…”

Adjuvant treatment for triple negative breast cancer with residual tumor after neo-adjuvant chemotherapy. A single institutional retrospective analysis

“…Before 2017, the use of post-neoadjuvant chemotherapy was not clearly supported by any scientific evidence. However the role of capecitabine in adjuvant setting for TNBC remains controversial [ 7 ].…”