Wu Yi-Long, Shi Yuankai, Tan Daniel Shao Weng, Xiaoqing Liu, Cheng Ying, Zhou Jianying, An Tong Tong, Lu You, Zhu Bo, Bai Chunxue, Passos Vanessa Q, Lau Yvonne Y, Xun Liao, Zhang Li
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Lung Cancer. 2020 Dec;150:240-246. doi: 10.1016/j.lungcan.2020.10.024. Epub 2020 Nov 5.
Patients with anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC) treated with crizotinib inevitably relapse, with brain as common site of progression.
ASCEND-6, a phase 1/2, single-arm study, included adult Chinese patients with stage IIIB or IV ALK+ NSCLC pretreated with crizotinib as the last therapy (irrespective of prior chemotherapies [≤2]). Primary endpoints were pharmacokinetics (PK), safety, and tolerability. Key secondary endpoint was overall response rate (ORR; investigator assessed).
Of the 103 enrolled patients, all received prior crizotinib, 70 % received ≥1 prior chemotherapy regimen, and 63.1 % had brain metastases at baseline. In the phase 1 component, 20 patients completed a 5-day PK run-in period. Median T (n = 16) was ∼6 h; geometric means of AUC (n = 16) and C (n = 16) at steady state were 22,000 ng*h/mL and 1080 ng/mL, respectively. In the final analysis, median follow-up time was 34 months (range: 27.8-40.6). The ORR was 41.7 % (95 % confidence interval [CI]: 32.1-51.9), and median progression-free survival was 7.2 months (95 % CI: 4.1-7.5). Median overall survival was 17.5 months (95 % CI: 10.8-24.3). Most frequent adverse events, regardless of study drug relationship (mostly grade 1/2), were diarrhea (74.8 %), vomiting (62.1 %), alanine transaminase increased (59.2 %), aspartate transaminase increased (58.3 %), and nausea (58.3 %).
Ceritinib PK in Chinese patients is consistent with those observed in the global ASCEND-1 study. Ceritinib was well tolerated and showed durable responses in Chinese patients with ALK+ NSCLC who progressed after crizotinib and ≤2 prior lines of chemotherapy.
接受克唑替尼治疗的间变性淋巴瘤激酶重排（ALK+）非小细胞肺癌（NSCLC）患者不可避免地会复发，脑是常见的进展部位。
ASCEND-6是一项1/2期单臂研究，纳入了成年中国患者，这些患者为IIIB期或IV期ALK+ NSCLC，之前接受过克唑替尼作为最后一种治疗（无论之前是否接受过化疗[≤2线]）。主要终点是药代动力学（PK）、安全性和耐受性。关键次要终点是总缓解率（ORR；研究者评估）。
103例入组患者均接受过克唑替尼治疗，70%接受过≥1线先前化疗方案，63.1%在基线时有脑转移。在1期部分，20例患者完成了为期5天的PK导入期。中位T（n = 16）约为6小时；稳态时AUC（n = 16）和C（n = 16）的几何均值分别为22,000 ng*h/mL和1080 ng/mL。在最终分析中，中位随访时间为34个月（范围：27.8 - 40.6个月）。ORR为41.7%（95%置信区间[CI]：32.1 - 51.9），中位无进展生存期为7.2个月（95% CI：4.1 - 7.5）。中位总生存期为17.5个月（95% CI：10.8 - 24.3）。无论与研究药物的关系如何（大多为1/2级），最常见的不良事件为腹泻（74.8%）、呕吐（62.1%）、谷丙转氨酶升高（59.2%）、谷草转氨酶升高（58.3%）和恶心（58.3%）。
色瑞替尼在中国患者中的PK与全球ASCEND-1研究中观察到的一致。色瑞替尼耐受性良好，在接受过克唑替尼和≤2线先前化疗后进展的中国ALK+ NSCLC患者中显示出持久疗效。
