Crizotinib to overcome alectinib-resistance in non-small cell lung cancer (NSCLC) harboring EML4-ALK.

• DOI: 10.1200/jco.2015.33.15_suppl.e19140
• Publication Date: 2019-04-19T20:26:11Z
• Authors: Hideko Isozaki; Eiki Ichihara; Nagio Takigawa; Toshiaki Sendo; Mitsune Tanimoto; Katsuyuki Kiura
• Keywords: Alectinib; ALK inhibitor

e19140 Background: Crizotinib, which is capable of blocking MET, ALK and ROS1, has been demonstrated the superior efficacy on first second line therapy for advanced/metastatic patients with NSCLC harboring EML4-ALK fusion gene compared chemotherapy. Alectinib, selective inhibitor also showed dramatic response rate, long duration acceptable toxic profile (Lancet Oncol 14, 2013: 590-98). Two randomized clinical trials comparing alectinib crizotinib in a first-line setting are ongoing. Alectinib would be key drug ALK-positive lung cancer treatment future. However, subsequent resistance to expected after its approval. Thus, we need consider therapeutic strategy overcome advance. To elucidate mechanisms alectinib-resistance, established resistant cell analyzed. Methods: alectinib-resistant ABC-11/CHR lines from ABC-11 genes were by continuous exposure alectinib. We characterized using MTT assay, Western blotting, immunohistochemistry, polymerase chain reaction, fluorescent situ hybridization, phospho-receptor tyrosine kinase array, RNA ELISA xenograft models. Results: cells 17-fold more than parent assay. The resitant activated MET increment ligand (hepatocyte growth factor) as an autocrine action. Because could inhibit well ALK, sensitive both vitro vivo. Conclusions: found that activation caused acquired combined AKK was effective such case. positive refractory might have benefits crizotinib.