第17屆肺癌世界大會(WCLC, World Conference on Lung Cancer)於2016年底在維也納舉辦，Poster Session中有一篇文章提供ALK癌友參考。若有自費吃Ceritinib(Zykadia, LDK378)的癌友，建議一定要看喔！
Phase 1 Study of Ceritinib 450 mg or 600 mg Taken with a Low-Fat Meal versus 750 mg in Fasted State in ALK+ Metastatic NSCLC
The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is approved at 750 mg fasted for the treatment of patients with ALK-rearranged (ALK+) metastatic non-small cell lung cancer (NSCLC) pretreated with crizotinib. The pharmacokinetic (PK) part of this study (Part 1) compares PK exposure of ceritinib following food consumption versus a fasted state in advanced ALK+ NSCLC patients.
Part 1 of this prospective, open-label, multicenter, randomized, 3-arm, phase 1 study (ASCEND-8; NCT02299505) is investigating PK and safety of ceritinib in advanced ALK+ NSCLC patients, treatment-naïve or pretreated with multiple lines of chemotherapy and/or crizotinib. Here, we compare steady-state PK of ceritinib 450 or 600 mg taken with a low‑fat meal versus ceritinib 750 mg fasted (primary endpoint) and report preliminary safety outcomes from Part 1. Part 2 continues to randomize treatment-naïve patients and will assess safety and efficacy.
As of June 16, 2016 (data cut-off), 137 patients were randomized in a 1:1:1 ratio to each treatment arm; 135 patients received one dose (safety set) and 97 patients had evaluable steady-state PK data. Disease characteristics were comparable between arms. Median follow-up duration was 4.14 months (range, 0.1–13.9). Relative to 750 mg fasted, the 450 mg fed arm demonstrated comparable steady-state PK, while the 600 mg fed arm showed ~25% higher steady-state PK (Table). Preliminary safety data suggests overall frequency of AEs and types of AEs were comparable between arms. However, incidences of gastrointestinal (GI)-related AEs (diarrhea, nausea or vomiting) were lowest, with no grade 3/4 GI AEs reported, in the 450 mg fed arm.
Steady-state PK was comparable in advanced ALK+ NSCLC patients taking ceritinib 450 mg with a low-fat meal versus 750 mg fasted. This study continues to enroll treatment-naïve patients into Part 2 to assess efficacy across the three treatment arms and assess longer safety follow-up.
本研究主要想了解Ceritinib不同服藥方式(空腹狀態 vs. 用餐後)下，藥物動力學的差異。
將ALK+病人分成三組：450mg Ceritinib (隨著低脂食物)、600mg Ceritinib(隨著低脂食物)、750mg Ceritinib(空腹狀態)。
*藥物副作用的定義是由美國癌症研究院制訂的 Common Terminology Criteria for Adverse Events (CTCAE, 又稱常見毒性標準), 用於描述病人接受癌症治療後，所發生器官毒性的嚴重度分級。分為輕微 (1級)、中級 (2級)、嚴重(3級), 或致命( 4級)、死亡 ( 5級)。