Evaluation of safety and efficacy of tivantinib in the treatment of inoperable or recurrent non-small-cell lung cancer
Massimo Broggini,1 Marina Chiara Garassino,2 Giovanna Damia1
1Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche "Mario Negri", 2Division of Medical Oncology, Fondazione IRCCS National Cancer Institute, Milan, Italy
Abstract: Tivantinib is a selective, oral, non-ATP-competitive, small molecule inhibitor of the c-Met receptor, tyrosine kinase, which is implicated at different levels of tumor cell migration, invasion, proliferation, and metastasis. Tivantinib has shown antitumor activity in various human tumor cell lines and in xenograft models of human cancers, including non-small-cell lung cancer. Few therapeutic options are available at present for advanced non-small-cell lung cancer, so there is a pressing need for new therapeutic strategies to improve response and survival. Amplification of Met has been reported in more than 20% of lung tumors that have acquired resistance to epidermal growth factor receptor inhibitors, implying that treatment of these tumors with a c-Met inhibitor should overcome resistance. Tivantinib has shown interesting and promising results in advanced non-small-cell lung cancer and appears to be well tolerated, either alone or in combination with other drugs. An interesting additional feature is the ability of the drug to delay development of new metastasis, in agreement with the proposed role of Met in this particular setting.
Keywords: non-small-cell lung cancer, Met inhibitors, tivantinib, biomarkers
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