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 journalArticlepeer-review

26 Citations (Scopus)

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 - 2019 Jul

Bibliographical note

Funding Information:
Disclosure: Dr. D.-W. Kim has received nonfinancial support from Novartis. Dr. Geater has received grants from Novartis; and has received personal fees from Astra Zeneca, Boehringer Ingelheim, and Roche. Dr. Postmus has received personal fees from Novartis, Bristol-Myers Squibb, Astra Zeneca, Abbvie, Roche, Boehringer Ingelheim, Merck Sharp & Dohme, G1 Therapeutics, and Janssen. Dr. Park has received personal fees from Novartis. Dr. Ardizzoni has received grants from Bristol-Myers Squibb and Celgene; and personal fees from Pfizer, Eli Lilly, Roche, and Merck Sharp & Dohme. Dr. de Castro has received personal fees from Novartis and Pfizer. Drs. Kiertsman, Chen, Lau, Viraswami-Appanna, and Passos are employees with and have stock in Novartis Pharmaceuticals Corporation. Dr. Dziadziuszko has received personal fees from Novartis, Roche, Pfizer, Tesaro, Astra Zeneca, Bristol-Myers Squibb, Ignyta, and Novacure. The remaining authors declare no conflict of interest.This study was funded by Novartis Pharmaceuticals Corporation. The authors thank the participating patients, their families, all of the study co-investigators, and research contributors. Medical writing support was provided by Shiva Krishna Rachamadugu, Novartis Healthcare Pvt Ltd. (Hyderabad, India). Disclosure: Dr. D.-W. Kim has received nonfinancial support from Novartis. Dr. Geater has received grants from Novartis; and has received personal fees from Astra Zeneca, Boehringer Ingelheim, and Roche. Dr. Postmus has received personal fees from Novartis, Bristol-Myers Squibb, Astra Zeneca, Abbvie, Roche, Boehringer Ingelheim, Merck Sharp & Dohme, G1 Therapeutics, and Janssen. Dr. Park has received personal fees from Novartis. Dr. Ardizzoni has received grants from Bristol-Myers Squibb and Celgene; and personal fees from Pfizer, Eli Lilly, Roche, and Merck Sharp & Dohme. Dr. de Castro has received personal fees from Novartis and Pfizer. Drs. Kiertsman, Chen, Lau, Viraswami-Appanna, and Passos are employees with and have stock in Novartis Pharmaceuticals Corporation. Dr. Dziadziuszko has received personal fees from Novartis, Roche, Pfizer, Tesaro, Astra Zeneca, Bristol-Myers Squibb, Ignyta, and Novacure. The remaining authors declare no conflict of interest.

Funding Information:
Disclosure: Dr. D.-W. Kim has received nonfinancial support from Novartis . Dr. Geater has received grants from Novartis; and has received personal fees from Astra Zeneca, Boehringer Ingelheim, and Roche. Dr. Postmus has received personal fees from Novartis, Bristol-Myers Squibb, Astra Zeneca, Abbvie, Roche, Boehringer Ingelheim, Merck Sharp & Dohme, G1 Therapeutics, and Janssen. Dr. Park has received personal fees from Novartis . Dr. Ardizzoni has received grants from Bristol-Myers Squibb and Celgene; and personal fees from Pfizer, Eli Lilly, Roche, and Merck Sharp & Dohme. Dr. de Castro has received personal fees from Novartis and Pfizer. Drs. Kiertsman, Chen, Lau, Viraswami-Appanna, and Passos are employees with and have stock in Novartis Pharmaceuticals Corporation. Dr. Dziadziuszko has received personal fees from Novartis, Roche, Pfizer, Tesaro, Astra Zeneca, Bristol-Myers Squibb, Ignyta, and Novacure. The remaining authors declare no conflict of interest.

Funding Information:
Disclosure: Dr. D.-W. Kim has received nonfinancial support from Novartis. Dr. Geater has received grants from Novartis; and has received personal fees from Astra Zeneca, Boehringer Ingelheim, and Roche. Dr. Postmus has received personal fees from Novartis, Bristol-Myers Squibb, Astra Zeneca, Abbvie, Roche, Boehringer Ingelheim, Merck Sharp & Dohme, G1 Therapeutics, and Janssen. Dr. Park has received personal fees from Novartis. Dr. Ardizzoni has received grants from Bristol-Myers Squibb and Celgene; and personal fees from Pfizer, Eli Lilly, Roche, and Merck Sharp & Dohme. Dr. de Castro has received personal fees from Novartis and Pfizer. Drs. Kiertsman, Chen, Lau, Viraswami-Appanna, and Passos are employees with and have stock in Novartis Pharmaceuticals Corporation. Dr. Dziadziuszko has received personal fees from Novartis, Roche, Pfizer, Tesaro, Astra Zeneca, Bristol-Myers Squibb, Ignyta, and Novacure. The remaining authors declare no conflict of interest.This study was funded by Novartis Pharmaceuticals Corporation. The authors thank the participating patients, their families, all of the study co-investigators, and research contributors. Medical writing support was provided by Shiva Krishna Rachamadugu, Novartis Healthcare Pvt Ltd. (Hyderabad, India).

Funding Information:
This study was funded by Novartis Pharmaceuticals Corporation . The authors thank the participating patients, their families, all of the study co-investigators, and research contributors. Medical writing support was provided by Shiva Krishna Rachamadugu, Novartis Healthcare Pvt Ltd. (Hyderabad, India).

Publisher Copyright:
© 2019 International Association for the Study of Lung Cancer

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

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