Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

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

2019; Elsevier BV; Volume: 14; Issue: 7 Linguagem: Inglês

10.1016/j.jtho.2019.03.002

1556-1380

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

Lung Cancer Research Studies

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