title: FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer.
abstract: On April 29, 2014, the FDA granted accelerated approval to ceritinib (ZYKADIA; Novartis Pharmaceuticals Corporation), a breakthrough therapy-designated drug, for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. The approval was based on a single-arm multicenter trial enrolling 163 patients with metastatic ALK-positive NSCLC who had disease progression on (91%) or intolerance to crizotinib. Patients received ceritinib at a starting dose of 750 mg orally once daily. The objective response rate (ORR) by a blinded independent review committee was 44% (95% CI, 36-52), and the median duration of response (DOR) was 7.1 months. The ORR by investigator assessment was similar. Safety was evaluated in 255 patients. The most common adverse reactions and laboratory abnormalities included diarrhea (86%), nausea (80%), increased alanine transaminase (80%), increased aspartate transaminase (75%), vomiting (60%), increased glucose (49%), and increased lipase (28%). Although 74% of patients required at least one dose reduction or interruption due to adverse reactions, the discontinuation rate due to adverse reactions was low (10%). With this safety profile, the benefit-risk analysis was considered favorable because of the clinically meaningful ORR and DOR.
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland. Sean.Khozin@fda.hhs.gov.
authors.forename: Sean
authors.initials: S
authors.lastname: Khozin
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Blumenthal
authors.affiliation: Office of Biostatistics, FDA, Silver Spring, Maryland.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Office of Biostatistics, FDA, Silver Spring, Maryland.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Tang
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland.
authors.forename: Margaret
authors.initials: M
authors.lastname: Brower
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland.
authors.forename: Emily
authors.initials: E
authors.lastname: Fox
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland.
authors.forename: Whitney
authors.initials: W
authors.lastname: Helms
authors.affiliation: Office of Translational Sciences, FDA, Silver Spring, Maryland.
authors.forename: Ruby
authors.initials: R
authors.lastname: Leong
authors.affiliation: Office of Translational Sciences, FDA, Silver Spring, Maryland.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Song
authors.affiliation: Office of Translational Sciences, FDA, Silver Spring, Maryland.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Office of Translational Sciences, FDA, Silver Spring, Maryland.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Office of Translational Sciences, FDA, Silver Spring, Maryland.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Office of Translational Sciences, FDA, Silver Spring, Maryland.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Office of New Drug Quality Assessment, FDA, Silver Spring, Maryland.
authors.forename: Donghao
authors.initials: D
authors.lastname: Lu
authors.affiliation: Office of New Drug Quality Assessment, FDA, Silver Spring, Maryland.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Office of New Drug Quality Assessment, FDA, Silver Spring, Maryland.
authors.forename: Ali
authors.initials: A
authors.lastname: Al Hakim
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland.
authors.forename: Karen
authors.initials: K
authors.lastname: Boyd
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.affiliation: Office of Hematology and Oncology Products, FDA, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D018570:Risk Assessment; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D011743:Pyrimidines; D013450:Sulfones; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib