The efficacy and safety of tivantinib in the treatment of solid tumors: a systematic review and meta-analysis
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Hao Zhang1,*, Zhengqiang Bao2,*, Hongwei Liao3, Wen Li1, Zhihua Chen1, Huahao Shen1 and Songmin Ying1,3
1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou, China
2Department of Cancer Center, The Second Hospital of Shandong University, Jinan, China
3Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, China
*These authors contributed equally to this work
Songmin Ying, email: [email protected]
Keywords: tivantinib, ARQ197, MET, NSCLC, hepatocellular carcinoma
Received: June 28, 2017 Accepted: October 03, 2017 Published: November 03, 2017
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.
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