Les patients ALK et ROS1 : quelle séquence ?

Abstract

Crizotinib, an inhibitor of ALK tyrosine kinase activity (ALKi), available as an oral compound is more efficient and better tolerated than chemotherapy, in first-line setting treatment of patients with metastatic non-small lung cancer with ALK rearrangement (NSCLC ALK+). A resistance occurs systematically. In one-third of cases such resistance comes from the emergence of clones with a resistance mutation in ALK gene sequence, while in half of the cases some bypass pathways become hyper-activated, when one third of cases consists of a brain progression. The new generation ALKi (ceritinib, alectinib, brigatinib, lorlatinib, ensartinib) show good efficacy for resistance to crizotinib. Alectinib and brigatinib, two second-generation ALKi, and lorlatinib, a third generation ALKi, all showed their superiority as compared with crizotinib, in first line setting treatment, in terms of progression-free survival, survival without brain progression and control of brain disease, in large phase 3 trials. Alectinib and brigatinib thus became the standard of care in frontline. Lorlatinib, is very efficient in first-line setting either and might become a new treatment option. Crizotinib remains the reference treatment in advanced NSCLC ROS1+. The treatment at relapse upon crizotinib in such NSCLC ROS1+ patients is not currently consensual.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.