title: Onartuzumab in lung cancer: the fall of Icarus?
abstract: The development of targeted therapies has led to a revolution in non-small-cell lung cancer, and opened up possibilities for improved personalized medicine. With the constant findings of new targets, a lot of inhibitors are being developed. However, reliable biomarkers are urgently needed. The design of clinical trials needs to become more flexible in order to obtain the best results and gain the US FDA/EMEA approval for the new drugs. A recent example of a failed trial is the Phase III MetLung trial that compared the effects of the c-MET monovalent antibody onartuzumab with erlotinib versus erlotinib alone in late-stage non-small-cell lung cancer. Here, we discuss several points as to why this trial could have failed.
authors.affiliation: Oncology Department, Phase I - Early Clinical Trials Unit, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.forename: Nele
authors.initials: N
authors.lastname: Van Der Steen
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D015195:Drug Design; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D057285:Precision Medicine
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000069347:Erlotinib Hydrochloride; C584058:onartuzumab
keywords: Phase I; c-MET; non-small-cell lung cancer; ornatuzumab; trial design