Lee Francis A S, Zee Benny Chung-Ying, Cheung Foon Yiu, Kwong Philip, Chiang Chi Leung, Leung Kwong Chuen, Siu Steven W K, Lee Conrad, Lai Maria, Kwok Chloe, Chong Marc, Jolivet Jacques, Tung Steward
*Department of Clinical Oncology, Tuen Mun Hospital †Division of Biostatistics and Centre for Clinical Research and Biostatistics, Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong ‡Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital §Department of Clinical Oncology, Queen Mary Hospital ∥Department of Clinical Oncology, Princess Margaret Hospital, Hong Kong ¶Aegera Therapeutics (Pharmascience Inc.), Montreal, QC, Canada.
Am J Clin Oncol. 2016 Dec;39(6):609-613. doi: 10.1097/COC.0000000000000099.
This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone.
Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile.
A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm.
AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.
本多中心、随机、开放标签的II期试验评估了AEG35156联合索拉非尼对比单独使用索拉非尼治疗晚期肝细胞癌（HCC）患者的疗效和安全性。
符合条件的患者按2:1的比例随机分组，分别接受AEG35156（每周静脉输注300mg）联合索拉非尼（每日口服400mg，分两次服用）或单独使用索拉非尼。主要终点为无进展生存期（PFS）。其他终点包括总生存期（OS）、客观缓解率（ORR）和安全性。
共纳入51例患者，其中48例可评估。中位随访16.2个月时，联合治疗组的中位PFS和OS分别为4.0个月（95%CI，1.2 - 4.1）和6.5个月（95%CI，3.9 - 11.5），索拉非尼组分别为2.6个月（95%CI，1.2 - 5.4）和5.4个月（95%CI，4.3 - 11.2）。根据方案中断研究治疗或进行剂量调整的患者，在PFS和OS方面明显优于联合治疗组中未降低剂量的患者以及索拉非尼组患者。联合治疗组基于Choi和RECIST标准的ORR分别为16.1%和9.7%。对照组的ORR为0。联合治疗组发生1例与药物相关的严重过敏不良事件，而索拉非尼组发生2例胃肠道严重不良事件。
AEG35156联合索拉非尼在ORR方面显示出额外活性，且耐受性良好。对PFS的益处中等，但在剂量降低的亚组中更明显。
