Capecitabine in Combination with Standard (Neo)Adjuvant Regimens in Early Breast Cancer: Survival Outcome from a Meta-Analysis of Randomized Controlled Trials.

Ze-Chun Zhang,Xu-Yuan Li,Sui-Ling Lin,Qi-Ni Xu,Hemant Kumar Bid

doi:10.1371/journal.pone.0164663

Ze-Chun Zhang, Xu-Yuan Li + Show 3 more

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https://doi.org/10.1371/journal.pone.0164663

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Abstract

Capecitabine has been investigated in early breast cancer in several studies, but it was undefined that whether it could improve survival. To investigate whether the addition of capecitabine affected survival in patients with early breast cancer, a meta-analysis was conducted and overall survival (OS), disease-free survival (DFS), and toxicity were assessed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for studies between January 2006 and April 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived. Seven trials with 9097 patients, consisted of 4 adjuvant and 3 neoadjuvant studies, were included in this meta-analysis. Adding capecitabine showed no improvement in DFS (HR = 0.93; 95% CI, 0.85–1.02; P = 0.12), whereas a significant improvement in OS was observed (HR = 0.85; 95% CI, 0.75–0.96; P = 0.008). A sub-analysis of DFS showed that benefit of capecitabine derived from patients with triple negative subtype and with extensive axillary involvement. Safety profiles were consistent with the known side-effects of capecitabine, but more patients discontinued scheduled treatment in the capecitabine group. Combining capecitabine with standard (neo)adjuvant regimens in early breast cancer demonstrated a significantly superior OS, and indicated DFS improvement in some subtypes with high risk of recurrence. Selection of subtypes was a key to identify patients who might gain survival benefit from capecitabine.

Highlights

Adjuvant polychemotherapy, mostly a regimen containing anthracycline and taxane, has been proved to reduce recurrence and death rate in breast cancer [1]
Seven phase III trials met the inclusion criteria of this meta-analysis [5, 6, 7, 8, 12, 13, 14], and 9,097 patients were included in the assessment of overall survival (OS), disease-free survival (DFS), and toxicity
The role of capecitabine in patients with metastatic breast cancer had been established [25], and studies were further conducted to test its efficacy in theadjuvant setting

Summary

Introduction

Mostly a regimen containing anthracycline and taxane, has been proved to reduce recurrence and death rate in breast cancer [1]. Neoadjuvant chemotherapy has no downside if clinical assessment suggests that patients with primary breast cancer will require systemic adjuvant therapy. No significant difference was found in overall survival or disease-free survival for adjuvant versus neoadjuvant chemotherapy [2]. The 5-year recurrence rate in early breast cancer is still as high as over 20% [3], which suggests probability for improvement. Capecitabine currently is considered one of the most active drugs available for advanced BC, which has a favorable safety profile. A phase III trial has demonstrated that the addition of capecitabine to the docetaxel advanced or metastatic breast cancer significantly prolonged the progression-free survival and overall survival [4]

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