Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset

Jpn J Clin Oncol. 2017 Jul 1;47(7):618-624. doi: 10.1093/jjco/hyx045.

Abstract

Introduction: 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.

Keywords: Clinical Trials; interventional therapy; lung medicine; thoracic; thoracic-others.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents / therapeutic use*
  • Asian Continental Ancestry Group / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Crizotinib
  • Disease-Free Survival
  • Female
  • Gene Order
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / therapeutic use*
  • Pyridines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Sulfones / therapeutic use*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Pyrimidines
  • Sulfones
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • ceritinib

Associated data

  • ClinicalTrials.gov/NCT01685060