The role of vascular epithelial growth factor receptor-tyrosine kinase inhibitors in the treatment of advanced breast cancer: a meta-analysis of 12 randomized controlled trials.

Abstract

AIM:

To perform a systematic review and meta-analysis of randomized controlled trials to determine the efficacy and toxicity of approved vascular epithelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in advanced breast cancer.

METHODS:

A comprehensive literature search for studies published up to August 2013 was performed. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.

RESULTS:

Twelve randomized controlled trials involved 3256 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that VEGFR-TKI therapy significantly improved ORR (RR 1.14, 95% CI: 1.03-1.28, p = 0.016), but it did not translate into benefits in PFS (HR 0.99, 95% CI: 0.81-1.22, p = 0.93) and OS (HR 1.11, 95% CI 0.99-1.24, p = 0.084) when compared to non-VEGFR-TKI therapy. Additionally, a higher incidence of grade 3 or 4 anemia, neutropenia, thrombocytopenia, diarrhea, hand-foot syndrome and fatigue was observed in VEGFR-TKI-based therapy.

CONCLUSIONS:

The VEGFR-TKI-based therapy offered a significant improvement in ORR in patients with advanced breast cancer but did not benefit PFS and OS. With present available data from randomized clinical trials, we were still unable to clearly set the role of VEGFR-TKIs in the treatment of metastatic breast cancer (MBC).

• Authors: Jianwen Li, Shengchao Huang, Wanting Zheng, Hongfei Ding, Yuanqi Zhang, Shuichuan Huang, Zhi Zhang, Baoying Chen, Zhongzeng Liang, Gan He, Xiongsheng Xiao, Siyi Li, Tuo Xu, Xiaodong Chen
• Journal: Current medical research and opinion (Curr Med Res Opin) Vol. 29 Issue 12 Pg. 1691-9 (Dec 2013) ISSN: 1473-4877 [Electronic] England
• PMID: 23981081 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)

Chemical References

• Neoplasm Proteins
• Protein Kinase Inhibitors
• Receptors, Vascular Endothelial Growth Factor

Topics

• Breast Neoplasms (drug therapy, enzymology)
• Female
• Humans
• Neoplasm Proteins (antagonists & inhibitors)
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Randomized Controlled Trials as Topic
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors)
• Risk Factors