New Molecular Targets for NSCLC

Conference Correspondent - ASCO 2014 - Lung Cancer


Results of clinical studies with several agents directed at novel molecular targets were also featured. Lenvatinib is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT, and PDGFR-B. In a double-blind, randomized, placebo-controlled study with 135 patients with nonsquamous (NS)?non-small-cell lung cancer (NSCLC) who had failed at least 2 prior therapies, treatment with lenvatinib once daily resulted in a median overall survival (OS) of 38.4 months and a median progression-free survival (PFS) of 20.9 weeks compared with 24.1 months and 7.9 weeks, respectively, with placebo (P <.001) (Havel L, et al. ASCO 2014. Abstract 8043). These data suggest that lenvatinib monotherapy may be a good option for heavily pretreated patients with NS-NSCLC. Another novel agent, patritumab (an anti-HER3 antibody), was tested in the HERALD study in combination with erlotinib in 215 patients with advanced NSCLC (Von Pawel J, et al. ASCO 2014. Abstract 8045). Compared with erlotinib alone, the combination therapy resulted in significantly longer median PFS and OS, but only in patients with high levels of HRG, suggesting that HRG is a predictive biomarker for patritumab and can be used to identify patients with advanced NSCLC who could benefit from this agent in combination with erlotinib.