Capecitabine in early breast cancer: A meta-analysis of randomised controlled trials

Eur J Cancer. 2017 May:77:40-47. doi: 10.1016/j.ejca.2017.02.024. Epub 2017 Mar 27.

Abstract

Purpose: Capecitabine is an effective therapy for metastatic breast cancer. Its role in early breast cancer is uncertain due to conflicting data from randomised controlled trials (RCTs).

Methods: PubMed and major conference proceedings were searched to identify RCTs comparing standard chemotherapy with or without capecitabine in the neoadjuvant or adjuvant setting. Hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS), as well as odds ratios (ORs) for toxicities were extracted or calculated and pooled in a meta-analysis. Subgroup analysis compared triple-negative breast cancer (TNBC) to non-TNBC and whether capecitabine was given in addition to or in place of standard chemotherapy. Meta-regression was used to explore the influence of TNBC on OS.

Results: Eight studies comprising 9302 patients were included. In unselected patients, capecitabine did not influence DFS (hazard ratio [HR] 0.99, p = 0.93) or OS (HR 0.90, p = 0.36). There was a significant difference in DFS when capecitabine was given in addition to standard treatment compared with in place of standard treatment (HR 0.92 versus 1.62, interaction p = 0.002). Addition of capecitabine to standard chemotherapy was associated with significantly improved DFS in TNBC versus non-TNBC (HR 0.72 versus 1.01, interaction p = 0.02). Meta-regression showed that adding capecitabine to standard chemotherapy was associated with improved OS in studies with higher proportions of patients with TNBC (R = -0.967, p = 0.007). Capecitabine increased grade 3/4 diarrhoea (odds ratio [OR] 2.33, p < 0.001) and hand-foot syndrome (OR 8.08, p < 0.001), and resulted in more frequent treatment discontinuation (OR 3.80, p < 0.001).

Conclusion: Adding capecitabine to standard chemotherapy appears to improve DFS and OS in TNBC, but increases adverse events in keeping with its known toxicity profile.

Keywords: Adjuvant chemotherapy; Breast cancer; Capecitabine; Meta-analysis; RCTs; Triple negative.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Capecitabine / therapeutic use*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / drug therapy

Substances

  • Antimetabolites, Antineoplastic
  • Capecitabine