title: Testing for anaplastic lymphoma kinase rearrangement to target crizotinib therapy: oncology, pathology and health economic perspectives.
abstract: Crizotinib is a first-in-class oral anaplastic lymphoma kinase (ALK) inhibitor targeting ALK-rearranged non-small-cell lung cancer. The therapy was approved by the US FDA in August 2011 and received conditional marketing approval by the European Commission in October 2012 for advanced non-small-cell lung cancer. A break-apart FISH-based assay was jointly approved with crizotinib by the FDA. This assay and an immunohistochemistry assay that uses a D5F3 rabbit monoclonal primary antibody were also approved for marketing in Europe in October 2012. While ALK rearrangement has relatively low prevalence, a clinical benefit is exhibited in more than 85% of patients with median progression-free survival of 8-10 months. In this article, the authors summarize the therapy and alternative test strategies for identifying patients who are likely to respond to therapy, including key issues for effective and efficient testing. The key economic considerations regarding the joint companion diagnostic and therapy are also presented. Given the observed clinical benefit and relatively high cost of crizotinib therapy, companion diagnostics should be evaluated relative to response to therapy versus correlation alone whenever possible, and both high inter-rater reliability and external quality assessment programs are warranted.
authors.affiliation: Altarum Institute, Ann Arbor, MI, USA. jim.lee@altarum.org
authors.forename: James A
authors.initials: JA
authors.lastname: Lee
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahel
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000191:economics / Q000473:pathology; D000077547:Crizotinib; D018572:Disease-Free Survival; D016527:Drug Costs; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000191:economics / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy / Q000191:economics / Q000473:pathology; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000191:economics / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases