Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial

Abstract

Purpose

Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.

Patients and Methods

We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.

Results

All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).

Conclusion

This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Keywords:

• adjuvant chemotherapy
• capecitabine
• SYSUCC-001
• triple-negative breast cancer
• TNBC

Abbreviations

TNBC, triple-negative breast cancer; DFS, disease-free survival; HR, hazard ratio; CI, confidence interval; A, doxorubicin; E, epirubicin; C, cyclophosphamide; T, paclitaxel (P) or docetaxel (D); M, methotrexate; F, 5-fluorouracil; NCCN, National Comprehensive Cancer Network; PD-1, programmed cell death protein 1; PD-L1, programmed cell death ligand 1.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Declarations

The present study was approved by the Ethics Committee of Sun Yat-sen University, and the requirement of obtaining written informed consent from the patients was waived owing to the retrospective nature of the study. Patients’ medical data were handled confidentially, and the study followed the Declaration of Helsinki.

Acknowledgments

The authors thank their departments and research teams for their help and dedication.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the National Natural Science Fund of China (No. 81974571) and the Found of “Double First-Class” and High-level University of Guangzhou University of Chinese Medicine (No. XKP2019002).