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Efficacy and Safety of Ceritinib (450 mg/d or 600 mg/d) With Food Versus 750-mg/d Fasted in Patients With ALK Receptor Tyrosine Kinase (ALK)-Positive NSCLC: Primary Efficacy Results From the ASCEND-8 Study.
- Source :
-
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2019 Jul; Vol. 14 (7), pp. 1255-1265. Date of Electronic Publication: 2019 Mar 07. - Publication Year :
- 2019
-
Abstract
- Introduction: In an earlier report of the ASCEND-8 study (open-label, phase I, three-arm study, treatment-naive patients and pre-treated patients with advanced/metastatic NSCLC), it was shown that ceritinib 450 mg with food had comparable exposure and better gastrointestinal tolerability than 750-mg fasted.<br />Methods: Here, we report efficacy and updated safety data from primary efficacy analysis of the ASCEND-8 study. Key secondary endpoints were overall response rate and duration of response, assessed by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors 1.1.<br />Results: In total, 306 patients were randomized to ceritinib 450-mg fed (n = 108) or 600-mg fed (n = 87) or 750-mg fasted (n = 111), of which 304 patients were included in safety analysis and 198 treatment-naive patients (ALK receptor tyrosine kinase [ALK]-positive by immunohistochemistry) were included in the efficacy analysis (450-mg fed [n = 73], 600-mg fed [n = 51], and 750-mg fasted [n = 74]). The BIRC-assessed overall response rate was 78.1% (95% confidence interval [CI]: 66.9-86.9), 72.5% (95% CI: 58.3-84.1), and 75.7% (95% CI: 64.3-84.9), respectively; and the median duration of response (months) by BIRC was not estimable (NE) (95% CI: 11.2-NE), 20.7 (95% CI: 15.8-NE), and 15.4 (95% CI: 8.3-NE), respectively. Based on the safety analysis (n = 304), the 450-mg fed arm showed the highest median relative dose intensity (100% versus 78.5% versus 83.7%), lowest proportion of patients with dose reductions (24.1% versus 65.1% versus 60.9%), and lowest proportion of patients with gastrointestinal toxicities (75.9% versus 82.6% versus 91.8%).<br />Conclusion: Ceritinib at a dose of 450 mg with food compared to 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity.<br /> (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Bone Neoplasms drug therapy
Bone Neoplasms genetics
Bone Neoplasms secondary
Brain Neoplasms drug therapy
Brain Neoplasms genetics
Brain Neoplasms secondary
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Female
Follow-Up Studies
Gene Rearrangement
Humans
Liver Neoplasms drug therapy
Liver Neoplasms genetics
Liver Neoplasms secondary
Lung Neoplasms genetics
Lung Neoplasms pathology
Male
Maximum Tolerated Dose
Middle Aged
Prognosis
Response Evaluation Criteria in Solid Tumors
Young Adult
Anaplastic Lymphoma Kinase genetics
Antineoplastic Agents therapeutic use
Carcinoma, Non-Small-Cell Lung drug therapy
Fasting
Food
Lung Neoplasms drug therapy
Pyrimidines therapeutic use
Sulfones therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1556-1380
- Volume :
- 14
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 30851442
- Full Text :
- https://doi.org/10.1016/j.jtho.2019.03.002