title: Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus.
abstract: Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC. This was due to the striking response data observed with crizotinib in phase I and II trials in patients with ALK-positive NSCLC, as well as the favorable tolerability and safety profile observed. Recently published phase III data established crizotinib as a new standard of care for this NSCLC molecular subset. A consequence of such rapid approval, however, is the limited clinical experience and relative paucity of information concerning optimal therapy management. In this review, we discuss the development of crizotinib and the clinical relevance of its safety profile, examining crizotinib-associated adverse events in detail and making specific management recommendations. Crizotinib-associated adverse events were mostly mild to moderate in severity in clinical studies, and appropriate monitoring and supportive therapies are considered effective in avoiding the need for dose interruption or reduction in most cases. Therapy management of patients following disease progression on crizotinib is also discussed. Based on available clinical data, it is evident that patients may have prolonged benefit from crizotinib after Response Evaluation Criteria in Solid Tumors-defined disease progression, and crizotinib should be continued for as long as the patient derives benefit.
authors.affiliation: Istituto Toscano Tumori, Livorno, Italy. Electronic address: f.cappuzzo@googlemail.com.
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.affiliation: Hôpital A. Michallon, Centre Hospitalier Universitaire, Grenoble, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Moro-Sibilot
authors.affiliation: Department of Oncology, Luzerner Kantonsspital, Luzern, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
authors.affiliation: The Royal Free Hospital, London, United Kingdom.
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Boleti
authors.affiliation: Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.affiliation: University of Groningen and University Medical Center Groningen, Department of Pulmonary Diseases, Groningen, The Netherlands.
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.affiliation: AZ Maria Middelares, Ghent, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Germonpré
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Meldgaard
authors.affiliation: Hospital del Mar, Barcelona, Spain.
authors.forename: Edurne
authors.initials: E
authors.lastname: Arriola
authors.affiliation: Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Steele
authors.affiliation: The Roy Castle Lung Cancer Foundation, Liverpool, United Kingdom.
authors.forename: Jesme
authors.initials: J
authors.lastname: Fox
authors.affiliation: Pfizer Oncology, New York, NY, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schnell
authors.affiliation: Pfizer Oncology, Pfizer Pharma GmbH, Berlin, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Engelsberg
authors.affiliation: Department of Internal Medicine, Centre for Integrated Oncology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D002986:Clinical Trials as Topic; D000077547:Crizotinib; D019468:Disease Management; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000628:therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014178:Translocation, Genetic
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
keywords: Anaplastic lymphoma kinase (ALK) inhibitor; Crizotinib; Non-small cell lung cancer (NSCLC); Safety profile; Therapy management; Treatment beyond progression