ASCEND-8 pharmacokinetic, safety, and efficacy data for ceritinib 450 mg with food in patients with anaplastic lymphoma kinase–positive non-small cell lung Cancer: A clinical perspective. (2019)

• Record Type: Journal Article
• Authors: Otoukesh, Salman; Sanchez, Tiffany; Mirshahidi, Saied; Wallace, Desiree; Mirshahidi, Hamid
• Is Part Of: Cancer treatment and research communications. Number 20(2019)
• Publication Date: 2019
• Subjects: Ceritinib -- Anaplastic lymphoma kinase -- Non-small cell lung cancer -- Food-effect trial -- Pharmacokinetics -- Gastrointestinal adverse events; AE adverse event -- ALK anaplastic lymphoma kinase -- ALK+ anaplastic lymphoma kinase positive -- AUC area under the plasma drug concentration–time curve -- AUCinf AUC from time 0 extrapolated to infinite time -- CI confidence interval -- Cmax maximum plasma drug concentration -- CNS central nervous system -- EML4-ALK echinoderm microtubule–associated protein-like 4-ALK -- FDA US Food and Drug Administration -- GI gastrointestinal -- NSCLC non-small cell lung cancer -- ORR overall response rate -- PFS progression-free survival -- PK pharmacokinetic -- QD once daily -- TKI tyrosine kinase inhibitor -- Tmax time to reach maximum plasma drug concentration
• DOI: 10.1016/j.ctarc.2019.100149
• Languages: English
• ISSNs: 2468-2942

Abstract

Highlights: The FDA-approved dosage of ceritinib was changed in 2017–450 mg taken with food. The new dosage may reduce gastrointestinal adverse events and dose modifications. Prescribing ceritinib 450 mg with food may positively impact patient management. Abstract: Anaplastic lymphoma kinase–positive ( ALK +) non-small cell lung cancer (NSCLC) is diagnosed in up to 126, 000 patients worldwide annually. Ceritinib is a next-generation ALK-targeted tyrosine kinase inhibitor that is approved for the treatment of patients with metastatic ALK + NSCLC. In December 2017, the US Food and Drug Administration–approved dose of ceritinib was changed from 750 mg/day under fasting conditions to 450 mg/day taken with food for the treatment of patients with ALK + NSCLC. This change was implemented on the basis of data from studies designed to investigate ways to reduce the frequency of gastrointestinal adverse events noted in patients enrolled in several ASCEND clinical trials that evaluated a ceritinib 750-mg fasted dose as either first- or second/third-line treatment. This review highlights and discusses published findings from the ASCEND-8 food-effect trial and includes commentary from physicians regarding their own clinical cases of patients who were enrolled in the trial and treated with either the 750-mg fasted or 450-mg fed dose of ceritinib. The review also discusses the implications of using the recently approved ceritinib 450-mg dose in the clinical setting.