Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
Masaryk Memorial Cancer Institute, Brno-střed-Staré Brno, Czech Republic.
J Thorac Oncol. 2019 Jul;14(7):1255-1265. doi: 10.1016/j.jtho.2019.03.002. Epub 2019 Mar 7.
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.
在 ASCEND-8 研究（开放标签、I 期、三臂研究、初治患者和预处理的晚期/转移性 NSCLC 患者）的早期报告中，显示与空腹 750 毫克相比，食物给予塞瑞替尼 450 毫克具有相当的暴露量和更好的胃肠道耐受性。
在此，我们报告 ASCEND-8 研究的主要疗效分析的疗效和更新的安全性数据。关键次要终点是总缓解率和缓解持续时间，由盲法独立审查委员会（BIRC）使用实体瘤反应评价标准 1.1 评估。
总共 306 名患者被随机分配至塞瑞替尼 450 毫克进食组（n=108）、600 毫克进食组（n=87）或 750 毫克空腹组（n=111），其中 304 名患者纳入安全性分析，198 名初治患者（免疫组织化学检测为 ALK 受体酪氨酸激酶 [ALK]阳性）纳入疗效分析（450 毫克进食组 [n=73]、600 毫克进食组 [n=51]、750 毫克空腹组 [n=74]）。BIRC 评估的总缓解率分别为 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 评估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）。基于安全性分析（n=304），进食 450 毫克组显示最高的中位相对剂量强度（100%比 78.5%比 83.7%）、最低的剂量减少患者比例（24.1%比 65.1%比 60.9%）和最低的胃肠道毒性患者比例（75.9%比 82.6%比 91.8%）。
与空腹 750 毫克相比，塞瑞替尼 450 毫克剂量与食物同服显示出一致的疗效和较少的胃肠道毒性。
