Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Cancer Med. 2021 Mar;10(5):1681-1689. doi: 10.1002/cam4.3771. Epub 2021 Feb 14.
Currently, there are no randomized trials on the effect of antiangiogenic therapy in patients with esophageal squamous cell carcinoma (ESCC). The following study investigated the efficacy and safety of anlotinib in patients with advanced ESCC who were previously treated with chemotherapy.
This randomized, placebo-controlled, double-blind phase 2 trial (NCT02649361) was conducted in 13 Chinese hospitals. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC who were previously treated with chemotherapy, and were randomly assigned (2:1) to receive oral anlotinib 12 mg or placebo on days 1-14 (repeated every 21 days). The primary endpoint was progression-free survival (PFS).
One hundred and sixty-five patients were randomly assigned to the anlotinib (n = 110) or the placebo (n = 55) arm. Median PFS was 3.02 months (95% CI 2.63-3.65) in the anlotinib group and 1.41 months (95% CI 1.38-1.41) in the placebo group (hazard ratio 0.46 [95% CI 0.32-0.66]; p < 0.001). The most common treatment-related adverse events of grade 3 or 4 were hypertension (17 [16%] patients), decreased appetite (6 [6%] patients), and hyponatremia (4 [4%] patients) in the anlotinib group and decreased appetite (2 [4%] patients) in the placebo group. Three (3%) deaths in the anlotinib group were considered as drug related, while there were no treatment-related deaths in the placebo group.
The use of anlotinib in previously treated, recurrent, or metastatic ESCC patients significantly improved PFS compared with placebo. Our findings suggest that antiangiogenesis might be an important therapeutic target in advanced ESCC.
Study of Anlotinib in Patients With Esophageal Squamous Cell Carcinoma (ALTER1102), NCT02649361.
目前，尚无抗血管生成治疗在食管鳞状细胞癌（ESCC）患者中的随机临床试验。本研究旨在探讨抗血管生成药物安罗替尼在既往接受过化疗的晚期 ESCC 患者中的疗效和安全性。
这是一项在中国 13 家医院开展的随机、安慰剂对照、双盲的 2 期临床试验（NCT02649361）。符合条件的患者为组织学确诊的复发性或转移性 ESCC 成年患者，既往接受过化疗，按 2:1 的比例随机分配（随机化）接受口服安罗替尼 12mg 或安慰剂治疗，每 21 天为一个周期。主要终点为无进展生存期（PFS）。
共有 165 例患者被随机分配至安罗替尼（n=110）或安慰剂（n=55）组。安罗替尼组中位 PFS 为 3.02 个月（95%CI 2.63-3.65），安慰剂组为 1.41 个月（95%CI 1.38-1.41）（风险比 0.46 [95%CI 0.32-0.66]；p<0.001）。安罗替尼组最常见的 3 级或 4 级治疗相关不良事件是高血压（17 例[16%]）、食欲下降（6 例[6%]）和低钠血症（4 例[4%]），安慰剂组是食欲下降（2 例[4%]）。安罗替尼组有 3 例（3%）死亡被认为与药物相关，而安慰剂组无治疗相关死亡。
在既往接受过治疗、复发或转移性 ESCC 患者中，安罗替尼治疗可显著提高 PFS，优于安慰剂。我们的研究结果表明，抗血管生成可能是晚期 ESCC 的一个重要治疗靶点。
ALTER1102 研究，安罗替尼治疗食管鳞状细胞癌患者的研究，NCT02649361。
