Byoung Chul Cho1, Radka Obermannova2, Alessandra Bearz3, Mark McKeage4, Dong-Wang Kim5, Ullas Batra6, Gloria Borra7, Sergey Orlov8, Sang-We Kim9, Sarayut L Geater10, Pieter E Postmus11, Scott A Laurie12, Keunchil Park13, Cheng-Ta Yang14, Andrea Ardizzoni15, Anna C Bettini16, Gilberto de Castro17, Flavia Kiertsman18, Zhe Chen18, Yvonne Y Lau18, Kalyanee Viraswami-Appanna18, Vanessa Q Passos18, Rafal Dziadziuszko19. 1. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: CBC1971@yuhs.ac. 2. Masaryk Memorial Cancer Institute, Brno-střed-Staré Brno, Czech Republic. 3. Centro di Riferimento Oncologico-IRCCS, Aviano, Italy. 4. University of Auckland, Auckland, New Zealand. 5. Seoul National University Hospital, Seoul, Republic of Korea. 6. Rajiv Gandhi Cancer Institute, Rohini, New Delhi, India. 7. Az. Osp. Univ.Maggiore della Carità, Italy. 8. State Pavlov Medical University, St. Petersburg, Russia. 9. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 10. Songklanagarind Hospital, Prince of Songkla University, Songkhla, Thailand. 11. The Clatterbridge Centre NHS Foundation Trust, Liverpool, United Kingdom. 12. Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada. 13. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 14. Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. 15. S.Orsola-Malpighi University Hospital, Bologna, Italy. 16. A.S.S.T. Papa Giovanni XXIII, Bergamo, Italy. 17. Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil. 18. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. 19. Rafal Dziadziuszko, Medical University of Gdansk, Gdansk, Poland.
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.
RCT Entities:
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.
Authors: Angelo Delmonte; Marco Angelo Burgio; Alberto Verlicchi; Giuseppe Bronte; Paola Cravero; Paola Ulivi; Giovanni Martinelli; Lucio Crinò Journal: Transl Lung Cancer Res Date: 2019-11
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Authors: Yuke Tian; Tian Tian; Ping Yu; Li Ren; Youling Gong; Wenxiu Yao; Xi Zhang; Jun Yin; Lang He; Li Chen; Ke Wang; Meijuan Huang; Juan Li Journal: Zhongguo Fei Ai Za Zhi Date: 2020-08-20