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
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
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DOI：
10.1016/j.jtho.2019.03.002
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发表时间：
2019-07-01
影响因子：
20.4
通讯作者：
Dziadziuszko, Rafal
中科院分区：
文献类型：
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作者：
Cho, Byoung Chul;Obermannova, Radka;Dziadziuszko, Rafal
简介：在 ASCEND-8 研究（开放标签、I 期、三组研究、初治患者和预先治疗的晚期/转移性 NSCLC 患者）的早期报告中，表明与餐后 450 mg 色瑞替尼相比，空腹服用 750 mg 具有相当的暴露量和更好的胃肠道耐受性。 方法：在此，我们报告来自 ASCEND-8 主要疗效分析的疗效和更新的安全性数据 学习。关键的次要终点是总体缓解率和缓解持续时间，由盲法独立审查委员会 (BIRC) 使用实体瘤疗效评估标准 1.1 进行评估。结果：总共 306 名患者被随机分配至色瑞替尼 450 mg 饭后服用 (n = 108) 或 600 mg 饭后服用 (n = 87) 或 750 mg 空腹服用 (n = 111)，其中 304 名患者被纳入安全组分析和 198 名初治患者 (ALK 受体酪氨酸激酶 [ALK] 免疫组织化学阳性）被纳入功效分析（450 mg 进食 [n = 73]、600 mg 进食 [n = 51] 和 750 mg 空腹 [n = 74]）。 BIRC评估的总体有效率分别为78.1%（95%置信区间[CI]：66.9-86.9）、72.5%（95% CI：58.3-84.1）和75.7%（95% CI：64.3-84.9）； BIRC 的中位缓解持续时间（月）分别为不可估计 (NE) (95% CI: 11.2-NE)、20.7 (95% CI: 15.8-NE) 和 15.4 (95% CI: 8.3-NE)。根据安全性分析（n = 304），450 mg 喂养组的中位相对剂量强度最高（100% vs 78.5% vs 83.7%），剂量减少的患者比例最低（24.1% vs 65.1% vs 60.9%），出现胃肠道毒性的患者比例最低（75.9% vs 82.6% vs 91.8%）。结论： 与空腹服用 750 mg 剂量的 450 mg 色瑞替尼相比，随餐服用剂量 450 mg 的色瑞替尼显示出一致的疗效和较低的胃肠道毒性。 (C) 2019 年国际肺癌研究协会。由爱思唯尔公司出版
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. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc.