title: Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset.
abstract: BACKGROUND
  Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer is sensitive to tyrosine kinase inhibitors; however, resistance can develop. Data are presented from the phase II trial (ASCEND-2) evaluating efficacy and safety in a subset of Japanese patients with ALK-rearranged non-small cell lung cancer previously treated with platinum-based chemotherapy, who experienced disease progression on crizotinib.
  
  
  METHODS
  Patients with advanced ALK-rearranged non-small cell lung cancer, including those with asymptomatic or neurologically stable baseline brain metastases, received oral ceritinib 750 mg/day. Whole-body and intracranial responses were assessed by investigator and Blinded Independent Review Committee (RECIST v1.1). Safety and tolerability were also investigated.
  
  
  RESULTS
  All 24 Japanese patients had received ≥2 previous treatment regimens, with crizotinib the last therapy received prior to ceritinib. Median duration of ceritinib exposure was 8.1 (range: 0.2-12.5) months. Overall response rate was 45.8% (95% confidence interval: 25.6-67.2). Other efficacy endpoints included disease control rate (79.2% [95% confidence interval: 57.8-92.9]), time to response (median 1.9 months [range: 1.7-3.5]), duration of response (median 9.2 months [95% confidence interval: 4.0-not estimable]) and progression-free survival (median 6.6 months [95% confidence interval: 3.7-9.3]). Of the four patients with active baseline target brain lesions, two achieved an intracranial partial response (50%). The most commonly reported adverse events (majority grade 1/2) were nausea (91.7%), diarrhea (83.3%) and vomiting (83.3%).
  
  
  CONCLUSIONS
  This study demonstrates the clinical activity and manageable tolerability of ceritinib in a Japanese subset of chemotherapy- and crizotinib-pretreated patients with ALK-rearranged non-small cell lung cancer who progressed on crizotinib, as was shown in the whole ASCEND-2 study population. ClinicalTrials.gov identifier: NCT01685060.
authors.affiliation: Department of Thoracic Oncology, Aichi Cancer Center, Nagoya.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.affiliation: Department of Thoracic Oncology, Hyogo Cancer Center, Akashi.
authors.forename: Miyako
authors.initials: M
authors.lastname: Satouchi
authors.affiliation: Department of Medical Oncology, Kindai University Hospital, Osaka.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Thoracic Oncology, Kyushu Cancer Center, Fukuoka.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Department of Allergy and Respiratory Medicine-Thoracic Oncology, Okayama University Hospital, Okayama.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.affiliation: Department of Thoracic Oncology, National Cancer Center, Tokyo.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka.
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Oncology Clinical Development and Medical Affairs Division, Novartis Pharma K.K., Tokyo.
authors.forename: Kota
authors.initials: K
authors.lastname: Tokushige
authors.affiliation: Oncology Clinical Development and Medical Affairs Division, Novartis Pharma K.K., Tokyo.
authors.forename: Ben
authors.initials: B
authors.lastname: Hatano
authors.affiliation: Thoracic Center - Thoracic Medical Oncology, The Cancer Institute Hospital of JFCR, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishio
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000077547:Crizotinib; D018572:Disease-Free Survival; D005260:Female; D023061:Gene Order; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013450:Sulfones / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib
keywords: Clinical Trials; interventional therapy; lung medicine; thoracic; thoracic-others