Abstract
Orally available crizotinib, an inhibitor of ALK tyrosine kinase activity (iALK), is more effective and better tolerated than first-line chemotherapy for the treatment of ALK rearranged lung cancer (ALK + NSCLC). Resistance to crizotinib occurs systematically and is due to resistance mutations in one third of the cases, bypass pathways in half of the cases and brain progression in one third of the cases. New generation iALKs (ceritinib, alectinib, brigatinib, lorlatinib, ensartinib) are effective in case of progression with crizotinib. This new generation crizotinib-iALK “classic” sequence allows medians of survival from the diagnosis of the metastatic disease largely exceeding 4 years. Alectinib and brigatinib, second generation iALK, and lorlatinib, third generation iALK, have been shown to be superior to crizotinib as a first-line treatment in terms of survival without and control of brain disease in trials of phase III. Alectinib and brigatinib are the standard of first-line treatment. Crizotinib is the gold standard for advanced ROS1 + NSCLCs. There is no consensus on treatment after relapse with crizotinib.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.
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