The efficacy and safety of tivantinib in the treatment of solid tumors: a systematic review and meta-analysis

Background: Tivantinib was designed to kill cancers by targeting the mesenchymal-epithelial transition (MET) protein. Although numerous tivantinib clinical trials are ongoing, tivantinib's efficacy and safety are still not clear. This meta-analysis was done to evaluate tivantinib's efficacy and safety in solid tumor treatment. Materials and Methods: PUBMED, EMBASE, and other databases were searched for eligible tivantinib clinical trials. The hazard ratio (HR) and 95% confidence interval (CI) of progression-free and overall survival (PFS and OS, respectively) were pooled and analyzed to evaluate tivantinib's efficacy. Data concerning adverse events (Grade >= 3) were pooled to calculate relative risks (RRs) with 95% CI for tivantinib-treated compared with control arms. Findings: Patients (1824) from six randomized control trials (RCTs) were enrolled. Compared with controls, tivantinib produced a significant improvement in PFS (HR, 0.73; 95% CI 0.65-0.83) but not in OS. In the non-small-cell lung cancer (NSCLC) subgroup, tivantinib combined with erlotinib prolonged patients' PFS when compared with controls (HR, 0.75; 95% CI, 0.65-0.86). In the white population, tivantinib also significantly improve PFS between treatment and control arms (HR, 0.75; 95% CI, 0.65-0.87). Tivantinib significantly improved OS in patients with high levels of MET expression. Tivantinib was shown to increase the risk of anemia and neutropenia. Interpretation: Tivantinib was better in prolonging PFS (not OS) in patients with solid tumors. High MET expression cancers may benefit from tivantinib. Tivantinib appeared to be well-tolerated by patients.