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Clinical Trial
. 2019 Jul;14(7):1255-1265.
doi: 10.1016/j.jtho.2019.03.002. Epub 2019 Mar 7.

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  1 , Radka Obermannova  2 , Alessandra Bearz  3 , Mark McKeage  4 , Dong-Wang Kim  5 , Ullas Batra  6 , Gloria Borra  7 , Sergey Orlov  8 , Sang-We Kim  9 , Sarayut L Geater  10 , Pieter E Postmus  11 , Scott A Laurie  12 , Keunchil Park  13 , Cheng-Ta Yang  14 , Andrea Ardizzoni  15 , Anna C Bettini  16 , Gilberto de Castro Jr  17 , Flavia Kiertsman  18 , Zhe Chen  18 , Yvonne Y Lau  18 , Kalyanee Viraswami-Appanna  18 , Vanessa Q Passos  18 , Rafal Dziadziuszko  19
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Free article
Clinical Trial

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 et al. J Thorac Oncol. 2019 Jul.
Free article

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.

Keywords: ALK receptor tyrosine kinase; Ceritinib; Food effect; NSCLC.

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