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Front-line treatment of ceritinib improves efficacy over crizotinib for Asian patients with anaplastic lymphoma kinase fusion NSCLC: The role of systemic progression control.

Authors
  • Huang, Shih-Hao1
  • Huang, Allen Chung-Cheng1
  • Wang, Chin-Chou2
  • Chang, Wen-Chen3
  • Liu, Chien-Ying1
  • Pavlidis, Stelios4
  • Ko, Ho-Wen1
  • Chung, Fu-Tsai1
  • Hsu, Ping-Chih1
  • Guo, Yi-Ke4
  • Kuo, Chih-Hsi Scott1, 4
  • Yang, Cheng-Ta1
  • 1 Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taipei, Taiwan. , (Taiwan)
  • 2 Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. , (Taiwan)
  • 3 Department of Medical Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan. , (Taiwan)
  • 4 Data Science Institute, Department of Computing, Imperial College London, London, UK.
Type
Published Article
Journal
Thoracic Cancer
Publisher
Wiley (Blackwell Publishing)
Publication Date
Dec 01, 2019
Volume
10
Issue
12
Pages
2274–2281
Identifiers
DOI: 10.1111/1759-7714.13221
PMID: 31613427
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Approximately 3%-5% of lung adenocarcinoma is driven by anaplastic lymphoma kinase (ALK) fusion oncogene, whose activity can be suppressed by multiple ALK inhibitors. Crizotinib and ceritinib have demonstrated superior efficacy to platinum-based chemotherapy as front-line treatment for patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the direct comparison between them in the front-line setting remains lacking. A total of 48 patients with ALK-positive, previously untreated advanced NSCLC, who received crizotinib and ceritinib as front-line treatment were retrospectively investigated. The efficacy and pattern of disease progression were analyzed. Patients receiving ceritinib treatment were significantly younger than those receiving crizotinib treatment (52.0 vs. 63.0, P = 0.016). The median progression-free survival (PFS) was significantly longer with ceritinib than with crizotinib treatment (32.3 vs. 12.9 months; log-rank P = 0.020); the hazard ratio for disease progression or death, 0.27 (95% CI, 0.08-0.90; P = 0.033). An objective response was noted in all patients in the ceritinib group and in 23 patients in the crizotinib group (74.2%; 95% CI, 59.0 to 88.5). The rate of systemic progression was significantly lower over time with ceritinib treatment compared to crizotinib treatment (cause-specific hazard ratio, 0.21; 95% CI 0.06-0.73; P = 0.014). Serious adverse events were noted in one (2.9%) patient showing elevated liver function in the crizotinib group and three (23.1%) patients showing diarrhea in the ceritinib group. Dose reduction was needed in five out of 13 (38.5%) patients receiving ceritinib treatment. Ceritinib showed higher efficacy associated with a better control of systemic progression compared to crizotinib for the front-line treatment of ALK-positive advanced NSCLCs. © 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

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