title: Diagnostic and therapeutic issues for patients with advanced non‑small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (review).
abstract: The recent availability of crizotinib in clinical practice, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) selected by the presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant implications for both the diagnostic phase and the treatment choices. In the United States, crizotinib was approved by the Food and Drug Administration (FDA) in 2011 for patients with ALK positivity detected by FDA-approved companion diagnostic test. As of January, 2014, the only FDA-approved diagnostic test is Vysis ALK Break-Apart FISH Probe Kit. In Europe, European Medicines Agency (EMA) approved crizotinib for ALK-positive patients in 2012, without specifying the type of test used for determining the positivity. FISH remains the reference technique for ALK determination, but, if fully validated, immunohistochemistry could challenge the current ALK screening practice. Given the robust evidence of activity of crizotinib in ALK-positive patients both pretreated and chemotherapy-naïve, and the favourable tolerability profile of the drug, many oncologists would prefer to administer the drug as early as possible. This is technically feasible in the United States, where crizotinib was approved well before the availability of the results of the randomized phase III trial comparing the drug with standard second-line chemotherapy, and the use of crizotinib in ALK-positive patients is not restricted to a specific line of treatment. On the contrary, in Europe, differently from the FDA decision, crizotinib cannot be used in chemotherapy-naïve patients. In both realities, a deeper knowledge of mechanisms of resistance, the role of repeated biopsies, the treatment strategy for patients experiencing disease progression with crizotinib, the choice of the best chemotherapy regimen are challenging topics for the management of ALK-positive patients in clinical practice.
authors.affiliation: Clinical Trials Unit, Istituto Nazionale dei Tumori Fondazione 'G. Pascale' - IRCCS, I-80131 Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.affiliation: Division of Thoracic Oncology, Istituto Europeo di Oncologia, I-20141 Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: De Marinis
authors.affiliation: University of Colorado Cancer Center, Aurora, CO 80045, USA.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.affiliation: Division of Medical Oncology, San Giuseppe Moscati Hospital, I-83100 Avellino, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D000077547:Crizotinib; D017277:Drug Approval; D005060:Europe; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases