Efficacy of Therapy with c-Met/HGF Inhibitors in Solid Tumors: A Systematic Review Based on 24 Clinical Trials

Background: The Mesenchymal Epithelial Transition factor (c -Met, MET) is the tyrosine kinase cell surface receptor, and the only known high affinity ligand is hepatocyte growth factor (HGF). HGF/MET pathway is required for not only normal physiologic development, but also a wide variety of human malignancies. More and more pieces of evidence have been identified for the treatment of a variety of malignancies with c-Met/HGF inhibitors. This review aims to more deeply understand the effects of c-Met/HGF inhibitors on patients with solid tumors and investigate the association between HGF/MET pathway biomarkers and survival. Methods: We carried out a review based on 24 published clinical trials to determine whether various kinds of c-Met/HGF inhibitors will benefit patients with solid tumors. We collected information about the tumor efficacy endpoint such as complete response, partial response, stable disease, objective responses and the objective response rate to assess clinical outcomes. Results: The biomarkers were analyzed for their relative efficacies. Interestingly, efficacy is quite different with each c-Met inhibitor, kind of solid tumor, and the combination with other antitumor agents and biomarkers. The outcomes of the biomarkers support the further exploration of c-Met/HGF as a prognostic marker. Conclusion: High quality studies with the identification and selection of the optimal patient populations are needed to further reveal the clinical effects of c-Met/HGF inhibitors and the development of a new generation of c-Met/HGF inhibitors is essential.