Multitargeted antiangiogenic tyrosine kinase inhibitors combined to chemotherapy in metastatic breast cancer: a systematic review and meta-analysis

We undertook a meta-analysis of randomized trials to evaluate the efficacy of multitargeted antiangiogenic tyrosine kinase inhibitors (MATKIs) in addition to chemotherapy in metastatic breast cancer. PubMed, Web of Knowledge databases and the ASCO meeting abstracts were searched for eligible literature published up to August 30, 2013. The endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and toxicities. Pooled hazard ratios (HRs) for survival outcomes and odds ratio (ORs) for dichotomous data with 95 % confidence intervals (CIs) were derived. Eight studies including 2,077 participants were analyzed. Compared to chemotherapy alone, adding MATKIs to chemotherapy resulted in a 14 % risk reduction of PFS events. However, the benefit did not reach statistical significance (HR 0.86; 95 % CI 0.70-1.04, P = 0.126). Also, no OS benefit was observed (HR 1.03; 95 % CI 0.89-1.18, P = 0.724). The addition of MATKIs significantly increased the ORR (OR 1.57; 95 % CI 1.30-1.91, P = 0.000). Subgroup analysis revealed that sorafinib showed a significantly greater effect on PFS in patients with HER2 negative metastatic breast cancer (HR 0.67; 95 % CI 0.55-0.82, P = 0.000) in comparison to chemotherapy alone. Additionally, sunitinib seemed to have no substantial efficacy for metastatic breast cancer. Toxicities were more frequent in patients receiving MATKIs. Overall, regimens consisting of MATKIs seemed not to be superior to chemotherapy alone in terms of PFS and OS, although significant improvement in ORR was observed. However, the addition of sorafenib significantly improved PFS. Further studies are needed to corroborate this finding.