title: Ceritinib: a new tyrosine kinase inhibitor for non-small-cell lung cancer.
abstract: OBJECTIVE
  To review ceritinib for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Literature searches were conducted in PubMed, EMBASE (1974 to July week 5, 2014), and Google Scholar using the terms ceritinib, LDK378, and non-small-cell lung cancer.
  
  
  METHODS
  One phase 1 trial and 2 abstracts were identified.
  
  
  RESULTS
  Ceritinib is approved for the treatment of ALK-positive metastatic NSCLC in patients who are intolerant to or have progressed despite therapy with crizotinib. In the phase 1 clinical trial, the maximum tolerated dose was determined to be 750 mg once daily. The overall response rate (ORR) was 58% (95% CI = 48-67) in patients who received ≥400 mg daily (n = 114). In this group, the ORR was 56% (95% CI = 41-67) and 62% (95% CI = 44-78) among crizotinib-exposed and -naïve patients, respectively. The ORR was 59% (95% CI = 47-70) in patients who received 750 mg daily (n = 78). The ORR was 56% (95% CI = 41-70) in crizotinib-treated patients and 64% (95% CI = 44-81) in crizotinib-naïve patients, respectively, in this subset. The median duration of response was 8.2 months. Median progression-free survival was 7.0 months. The most common adverse reactions included diarrhea, nausea, vomiting, abdominal pain, anorexia, constipation, fatigue, and elevated transaminases.
  
  
  CONCLUSIONS
  Ceritinib has activity in crizotinib-resistant and crizotinib-naïve patients and appears to be a viable alternative for ALK-positive NSCLC. Long-term data are needed to further define the role of ceritinib in the treatment of NSCLC.
authors.affiliation: MCPHS University, Manchester, NH, USA maryann.cooper@mcphs.edu.
authors.forename: Maryann R
authors.initials: MR
authors.lastname: Cooper
authors.affiliation: MCPHS University, Manchester, NH, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Chim
authors.affiliation: MCPHS University, Manchester, NH, USA.
authors.forename: Hoyi
authors.initials: H
authors.lastname: Chan
authors.affiliation: MCPHS University, Manchester, NH, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Durand
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D017321:Clinical Trials, Phase I as Topic; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009325:Nausea / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013450:Sulfones; C586847:ceritinib
keywords: antineoplastics; basic; cancer; oncology; pharmacokinetics; pharmacology