Multikinase inhibitor in combination with chemotherapy in the treatment of advanced breast cancer-a meta-analysis

Background: Multikinase inhibitors in combination with chemotherapy have recently been evaluated in patients with advanced breast cancer (ABC) in the adjuvant treatment, but limited data are available. We performed a meta-analysis of prospective randomized controlled trials to evaluate both the efficacy and safety of approved multikinase inhibitors combined with chemotherapy in the treatment of ABC. Methods: Relevant literature search were performed comprehensively up to June 2015. The endpoints were progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The available data were pooled and evaluated using Stata 12.0 (StataCorp, College Station, USA). Results: Seven randomized controlled trials (RCTs) with 1694 patients were included. Our pooled results showed that, compared to chemotherapy alone, multikinase inhibitors in combination with chemotherapy improved the PFS [hazard ratio (HR), 0.74; 95% confidence interval (CI), 0.63-0.84; P<0.001] and ORR [odds ratios (OR), 1.66; 95% CI, 1.35-2.05; P<0.001], but this did not correspond to an improvement in OS (HR, 1.02; 95% CI, 0.84-1.19; P<0.001). Additionally, a higher incidence of grades 3/4 hypertension, diarrhea, hand-foot syndrome, rash, stomatitis, and mucositis were observed in multikinase inhibitor-based therapy. Conclusions: Our results suggested that the combination of multikinase inhibitors and chemotherapy benefits ABC patients in PFS and ORR, but not OS, and may also have resulted in increased AEs.