title: U.S. Food and Drug Administration approval: crizotinib for treatment of advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive.
abstract: On August 26, 2011, the U.S. Food and Drug Administration (FDA) approved crizotinib (XALKORI Capsules, Pfizer Inc.) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as detected by an FDA-approved test. The Vysis ALK Break-Apart FISH Probe Kit (Abbott Molecular, Inc.) was approved concurrently. In two multicenter, single-arm trials, patients with locally advanced or metastatic ALK-positive NSCLC previously treated with one or more systemic therapies received crizotinib orally at a dose of 250 mg twice daily. In 119 patients with ALK-positive NSCLC by local trial assay, the objective response rate (ORR) was 61% [95% confidence intervals (CI), 52%-70%] with a median response duration of 48 weeks. In 136 patients with ALK-positive NSCLC by the to-be-marketed test, the ORR was 50% (95% CI, 42%-59%) with a median response duration of 42 weeks. The most common adverse reactions (≥25%) were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Accelerated approval was granted on the basis of the high ORRs and durable responses. On November 20, 2013, crizotinib received full approval based on an improvement in progression-free survival in patients with metastatic ALK-positive NSCLC previously treated with one platinum-based chemotherapy regimen.
authors.affiliation: Authors' Affiliations: Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda; Offices of Hematology and Oncology Products, Biostatistics, and Clinical Pharmacology, Center for Drug Evaluation and Research; and Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiologic Health; U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Shakun M
authors.initials: SM
authors.lastname: Malik
authors.forename: Virginia Ellen
authors.initials: VE
authors.lastname: Maher
authors.forename: Karen E
authors.initials: KE
authors.lastname: Bijwaard
authors.forename: Robert L
authors.initials: RL
authors.lastname: Becker
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Shenghui W
authors.initials: SW
authors.lastname: Tang
authors.forename: Pengfei
authors.initials: P
authors.lastname: Song
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Anshu
authors.initials: A
authors.lastname: Marathe
authors.forename: Brenda
authors.initials: B
authors.lastname: Gehrke
authors.forename: Whitney
authors.initials: W
authors.lastname: Helms
authors.forename: Diane
authors.initials: D
authors.lastname: Hanner
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D000077547:Crizotinib; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D017277:Drug Approval; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; 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 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D014786:Vision Disorders / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
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