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

Byoung Chul Cho, Radka Obermannova, Alessandra Bearz, Mark McKeage, Dong Wang Kim, Ullas Batra, Gloria Borra, Sergey Orlov, Sang We Kim, Sarayut L. Geater, Pieter E. Postmus, Scott A. Laurie, Keunchil Park, Cheng Ta Yang, Andrea Ardizzoni, Anna C. Bettini, Gilberto de Castro, Flavia Kiertsman, Zhe Chen, Yvonne Y. LauKalyanee Viraswami-Appanna, Vanessa Q. Passos, Rafal Dziadziuszko

Research output: Contribution to journalArticle

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. 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. 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%). Conclusion: Ceritinib at a dose of 450 mg with food compared to 750-mg fasted showed consistent efficacy and less gastrointestinal toxicity.

Original languageEnglish
Pages (from-to)1255-1265
Number of pages11
JournalJournal of Thoracic Oncology
Volume14
Issue number7
DOIs
Publication statusPublished - Jul 2019

Keywords

  • ALK receptor tyrosine kinase
  • Ceritinib
  • Food effect
  • NSCLC

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Cho, B. C., Obermannova, R., Bearz, A., McKeage, M., Kim, D. W., Batra, U., Borra, G., Orlov, S., Kim, S. W., Geater, S. L., Postmus, P. E., Laurie, S. A., Park, K., Yang, C. T., Ardizzoni, A., Bettini, A. C., de Castro, G., Kiertsman, F., Chen, Z., ... Dziadziuszko, R. (2019). 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. Journal of Thoracic Oncology, 14(7), 1255-1265. https://doi.org/10.1016/j.jtho.2019.03.002