A new drug in thoracic oncology: MetMab (onartuzumab)

Met pathway is activated in many solid cancers. In advanced non-small cell lung cancer (NSCLC), Met amplification is involved in 5 to 20% of acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in tumors with initially sensitive EGFR mutation. MetMab (onartuzumab) is a monoclonal single-arm humanized anti-Met antibody. Its fixation on the Met receptor prevents the binding of the ligand (Hepatocyte Growth factor [HGF]) and the signal transduction. After promising results in preclinical and phase I trials, a randomized phase II trial has been conducted in advanced NSCLC in 2nd or 3rd line treatment. One hundred and twenty-eight patients have been randomized between an association of erlotinib+placebo and erlotinib+MetMab (15mg/kg IV every 3 weeks) until progression or toxicity. Patients with overexpression of Met in immunohistochemistry (IHC) had a progression-free survival (PFS) and an overall survival (OS) two-fold (median 1.5 versus 2.9 months; HR=0.53; P=0.04) and three-fold (median 3.8 versus 12.6 months; HR=0.37; P=0.002) longer, respectively, than patients with negative IHC score. The erlotinib+MetMab association had a worse effect on SSP and OS than the control arm in patients with negative IHC. The toxicity profile of MetMab is very good, and the main adverse effect is the occurrence of peripheral edemas, most of the time of low grade. A randomized phase III is on going to validate these results.