title: Receptor kinase inhibitors target NSCLC: two antibodies and a small-molecule MET inhibitor.
abstract: Joining cetuximab, sorafenib, afatinib, intedanib, and crizotinib in phase III development for non-small cell lung cancer (NSCLC) are ramucirumab (developed by ImClone, a subsidiary of Lilly), necitumumab (developed by ImClone and Bristol-Myers Squibb), and tivantinib (ARQ 197, developed by ArQule and Daiichi Sankyo). Necitumumab is a second-generation anti-EGFR monoclonal antibody (mAb) similar to cetuximab. Enrollment has been stopped in one of two necitumumab phase III trials because of safety concerns. Ramucirumab is an anti-VEGFR2 mAb targeting the same pathway as bevacizumab. Although the phase II safety data for ramucirumab appear better than the data for necitumumab, fewer phase III data are available. Tivantinib is a highly selective, orally available MET tyrosine kinase inhibitor. MET is overexpressed in 61% of NSCLC cases. Although tivantinib is the last of the three agents discussed here to enter phase III, its phase II results are the most robust.
authors.affiliation: inThought Research, Wolters Kluwer Pharma Solutions, Yardley, PA, USA. david.yee@wolterskluwer.com
authors.forename: David
authors.initials: D
authors.lastname: Yee
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D011760:Pyrrolidinones; D011804:Quinolines; D000096662:Ramucirumab; C551661:ARQ 197; C527969:necitumumab