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

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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
StatePublished - Jul 2019

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Safety
Food
Confidence Intervals
Advisory Committees
ceritinib
anaplastic lymphoma kinase
Immunohistochemistry
Therapeutics

Keywords

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

Cite this

Cho, Byoung Chul ; Obermannova, Radka ; Bearz, Alessandra ; McKeage, Mark ; Kim, Dong Wang ; Batra, Ullas ; Borra, Gloria ; Orlov, Sergey ; Kim, Sang We ; Geater, Sarayut L. ; Postmus, Pieter E. ; Laurie, Scott A. ; Park, Keunchil ; Yang, Cheng Ta ; Ardizzoni, Andrea ; Bettini, Anna C. ; de Castro, Gilberto ; Kiertsman, Flavia ; Chen, Zhe ; Lau, Yvonne Y. ; Viraswami-Appanna, Kalyanee ; Passos, Vanessa Q. ; Dziadziuszko, Rafal. / 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. In: Journal of Thoracic Oncology. 2019 ; Vol. 14, No. 7. pp. 1255-1265.
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title = "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",
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",
author = "Cho, {Byoung Chul} and Radka Obermannova and Alessandra Bearz and Mark McKeage and Kim, {Dong Wang} and Ullas Batra and Gloria Borra and Sergey Orlov and Kim, {Sang We} and Geater, {Sarayut L.} and Postmus, {Pieter E.} and Laurie, {Scott A.} and Keunchil Park and Yang, {Cheng Ta} and Andrea Ardizzoni and Bettini, {Anna C.} and {de Castro}, Gilberto and Flavia Kiertsman and Zhe Chen and Lau, {Yvonne Y.} and Kalyanee Viraswami-Appanna and Passos, {Vanessa Q.} and Rafal Dziadziuszko",
year = "2019",
month = "7",
doi = "10.1016/j.jtho.2019.03.002",
language = "English",
volume = "14",
pages = "1255--1265",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "7",

}

Cho, BC, Obermannova, R, Bearz, A, McKeage, M, Kim, DW, Batra, U, Borra, G, Orlov, S, Kim, SW, Geater, SL, Postmus, PE, Laurie, SA, Park, K, Yang, CT, Ardizzoni, A, Bettini, AC, de Castro, G, Kiertsman, F, Chen, Z, Lau, YY, Viraswami-Appanna, K, Passos, VQ & 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, vol. 14, no. 7, pp. 1255-1265. https://doi.org/10.1016/j.jtho.2019.03.002

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

In: Journal of Thoracic Oncology, Vol. 14, No. 7, 07.2019, p. 1255-1265.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

T2 - Primary Efficacy Results From the ASCEND-8 Study

AU - Cho, Byoung Chul

AU - Obermannova, Radka

AU - Bearz, Alessandra

AU - McKeage, Mark

AU - Kim, Dong Wang

AU - Batra, Ullas

AU - Borra, Gloria

AU - Orlov, Sergey

AU - Kim, Sang We

AU - Geater, Sarayut L.

AU - Postmus, Pieter E.

AU - Laurie, Scott A.

AU - Park, Keunchil

AU - Yang, Cheng Ta

AU - Ardizzoni, Andrea

AU - Bettini, Anna C.

AU - de Castro, Gilberto

AU - Kiertsman, Flavia

AU - Chen, Zhe

AU - Lau, Yvonne Y.

AU - Viraswami-Appanna, Kalyanee

AU - Passos, Vanessa Q.

AU - Dziadziuszko, Rafal

PY - 2019/7

Y1 - 2019/7

N2 - 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.

AB - 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.

KW - ALK receptor tyrosine kinase

KW - Ceritinib

KW - Food effect

KW - NSCLC

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U2 - 10.1016/j.jtho.2019.03.002

DO - 10.1016/j.jtho.2019.03.002

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