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- Marie Viala, Solenn Brosseau, David Planchard, Benjamin Besse, and Jean-Charles Soria.
- Institut Gustave-Roussy, département d'innovation thérapeutique et d'essais précoces, 94805 Villejuif, France; CHU de Clermont-Ferrand, oncologie médicale, 63011 Clermont-Ferrand, France.
- Bull Cancer. 2015 Apr 1; 102 (4): 381-9.
AbstractThe identification of the EML4-ALK rearrangement in 5% of NSCLC enhanced the development of 1st generation ALK inhibitors such as crizotinib. Two phase III trials demonstrated crizotinib efficacy in second line metastatic (PROFILE 1007) and more recently first line metastatic (PROFILE 1014) NSCLC in terms of progression-free survival and also objective response. However, within 12 to 16 months, patients will progress due to the emergence of acquired resistance mechanisms such as mutation (L1196M) or amplification of the ALK gene, as well as activation of alternative signaling pathways (EGFR, KRAS). Second generation ALK inhibitors have been developed such as ceritinib, alectinib, and AP26113. This review will present those new drugs, summarize the results of their ongoing trials, and discuss the best way to treat ALK+ NSCLC patients. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
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