An ALK Inhibitor in Crizotinib-Resistant NSCLC

Conference Correspondent - ASCO 2014 - Lung Cancer


AP26113 is a novel, orally active tyrosine kinase inhibitor with activity against ALK and crizotinib-resistant mutants. This agent was tested in 106 patients with advanced ALK+ NSCLC who progressed on crizotinib therapy (Gettinger SN, et al. ASCO 2014. Abstract 8047). After a median follow-up of 3.6 months, 63% of the patients responded with a median progression-free survival of 47 weeks. A radiologic review of 10 patients with progressing brain metastases showed that 6 patients had a response in the brain, with 4 of these patients having no detectable brain metastases after therapy with AP26113. The most common treatment-emergent adverse events in the treated patients were nausea, diarrhea, fatigue, cough, and headache, mainly Grade 1 or 2. These data suggest that AP26113 is a promising agent for patients with crizotinib-resistant, ALK+, advanced NSCLC, but further testing in randomized clinical trials is needed.