title: The European medicines agency review of bosutinib for the treatment of adult patients with chronic myelogenous leukemia: summary of the scientific assessment of the committee for medicinal products for human use.
abstract: On March 27, 2013, a conditional marketing authorization valid throughout the European Union was issued for bosutinib (Bosulif) for the treatment of adult patients with chronic-phase, accelerated-phase, and blast-phase Philadelphia chromosome positive (Ph⁺) chronic myelogenous leukemia (CML) previously treated with one tyrosine kinase inhibitor or more and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options. Bosutinib is a kinase inhibitor that targets the BCR-ABL kinase. The recommended dose is 500 mg of bosutinib once daily. The main evidence of efficacy for bosutinib was based on a CML subgroup analysis of study 3160A4-200, a phase I/II study of bosutinib in Ph⁺ leukemia in imatinib-resistant or intolerant CML. The subgroup was defined based on the presence of a BCR-ABL kinase domain mutation that would be expected to confer resistance to dasatinib (F317, E255) or nilotinib (E255, Y253, F359) and expected to have sensitivity to bosutinib or based on the presence of medical conditions or prior toxicities that may predispose the patient to unacceptable risk in the setting of nilotinib or dasatinib therapy. A conditional marketing authorization was granted because of the limited evidence of efficacy and safety currently supporting this last-line indication.
authors.affiliation: European Medicines Agency, London, United Kingdom; Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany; Agencia Española de Medicamentos y Productos Sanitarios, Servicio de Farmacología Clínica, Hospital Puerta de Hierro, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hanaizi
authors.forename: Christoph
authors.initials: C
authors.lastname: Unkrig
authors.forename: Harald
authors.initials: H
authors.lastname: Enzmann
authors.forename: Jorge
authors.initials: J
authors.lastname: Camarero
authors.forename: Arantxa
authors.initials: A
authors.lastname: Sancho-Lopez
authors.forename: Tomas
authors.initials: T
authors.lastname: Salmonson
authors.forename: Christian
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: Edward
authors.initials: E
authors.lastname: Laane
authors.forename: Francesco
authors.initials: F
authors.lastname: Pignatti
mesh_terms: D000814:Aniline Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D017277:Drug Approval; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005060:Europe; D005062:European Union; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000814:Aniline Compounds; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C471992:bosutinib; D016044:Fusion Proteins, bcr-abl
keywords: Bosulif; Bosutinib; Chronic myelogenous leukemia; EMA; European Medicines Agency