title: [Second generation ALK inhibitors in non-small cell lung cancer: systemic review].
abstract: The 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.
authors.affiliation: Institut Gustave-Roussy, département d'innovation thérapeutique et d'essais précoces, 94805 Villejuif, France; CHU de Clermont-Ferrand, oncologie médicale, 63011 Clermont-Ferrand, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Viala
authors.affiliation: Institut Gustave-Roussy, département d'innovation thérapeutique et d'essais précoces, 94805 Villejuif, France; CHU de Caen, pneumologie, 14033 Caen, France.
authors.forename: Solenn
authors.initials: S
authors.lastname: Brosseau
authors.affiliation: Institut Gustave-Roussy, département de médecine oncologique, 94805 Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.affiliation: Institut Gustave-Roussy, département de médecine oncologique, 94805 Villejuif, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.affiliation: Institut Gustave-Roussy, département d'innovation thérapeutique et d'essais précoces, 94805 Villejuif, France; Institut Gustave-Roussy, département de médecine oncologique, 94805 Villejuif, France; Université Paris-Sud, 75011 Paris, France. Electronic address: jean-charles.soria@gustaveroussy.fr.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D006801:Humans; D000077548:Anaplastic Lymphoma Kinase; D002227:Carbazoles / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics; D017326:Clinical Trials, Phase III as Topic; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000032:analysis; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D013450:Sulfones / Q000627:therapeutic use
chemical_list: C582670:alectinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C000598580:brigatinib; D002227:Carbazoles; C586847:ceritinib; D000077547:Crizotinib; C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion; D009943:Organophosphorus Compounds; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D020794:Receptor Protein-Tyrosine Kinases; D013450:Sulfones
keywords: ALK; ALK inhibitors; Cancer bronchique non à petites cellules; Crizotinib; Inhibiteurs de ALK; Mécanismes de résistance; NSCLC; Resistance mechanisms