Jin Li, Weijian Guo, Xiaodong Zhu, Dongmei Ji, and Xin Liu, Shanghai Cancer Center and Shanghai Medical College, Fudan University; Liwei Wang, Shanghai First People's Hospital; Leizhen Zheng, XinHua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai; Shukui Qin, The 81 Hospital of PLA, Nanjing; Hao Yu, School of Public Health, Nanjing Medical University, Nanjing; Jianming Xu, The 307 Hospital of the Academy of Military Medical Sciences, Beijing; Jianping Xiong, The First Affiliated Hospital of Nanchang University, Nanchang; Yuxian Bai, The Third Affiliated Hospital of Harbin Medical University, Harbin; Guoping Sun, The First Affiliated Hospital of Anhui Medical University, Hefei; Yan Yang, Gansu Cancer Hospital, Lanzhou; Nong Xu, The First Affiliated Hospital of Zhejiang University, Hangzhou; Ying Cheng, Jilin Cancer Hospital, Changchun; Zhehai Wang, Shandong Cancer Hospital, Jinan; and Min Tao, The First Affiliated Hospital of Soochow University, Suzhou, China.
J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.
Patients with metastatic gastric cancer (mGC) who do not respond to or who experience progression with second-line chemotherapy have no treatment options that clearly confer a survival benefit. This trial investigated the safety and efficacy of apatinib, an inhibitor of vascular endothelial growth factor receptor, as a treatment option for heavily pretreated patients with mGC.
Patients who experienced treatment failure with at least two chemotherapeutic regimens were randomly assigned to receive placebo (group A), apatinib 850 mg once daily (group B), or apatinib 425 mg twice daily (group C).
We enrolled 144 patients onto this study. In groups A, B, and C, the median overall survival (OS) times were 2.50 months (95% CI, 1.87 to 3.70 months), 4.83 months (95% CI, 4.03 to 5.97 months), and 4.27 months (95% CI, 3.83 to 4.77 months), respectively, and the median progression-free survival (PFS) times were 1.40 months (95% CI, 1.20 to 1.83 months), 3.67 months (95% CI, 2.17 to 6.80 months), and 3.20 months (95% CI, 2.37 to 4.53 months), respectively. There were statistically significant differences between the apatinib and placebo groups for both PFS (P < .001) and OS (P < .001 and P = .0017). Nine patients had a partial response (three patients in group B and six patients in group C). Toxicities were tolerable or could be clinically managed. The most common grade 3 to 4 adverse events were hand-foot syndrome and hypertension. Hematologic toxicities were moderate, and grade 3 to 4 hematologic toxicities were rare.
Apatinib showed improved PFS and OS in heavily pretreated patients with mGC who had experienced treatment failure with two or more chemotherapy regimens.
对于二线化疗无效或进展的转移性胃癌（mGC）患者，尚无明确能带来生存获益的治疗方案。本试验旨在研究血管内皮生长因子受体抑制剂阿帕替尼作为一种治疗选择，对于经过大量预处理的 mGC 患者的安全性和有效性。
至少接受两种化疗方案治疗失败的患者被随机分配接受安慰剂（A 组）、阿帕替尼 850mg 每日一次（B 组）或阿帕替尼 425mg 每日两次（C 组）。
本研究共纳入 144 例患者。在 A、B 和 C 组中，中位总生存期（OS）分别为 2.50 个月（95%CI，1.87 至 3.70 个月）、4.83 个月（95%CI，4.03 至 5.97 个月）和 4.27 个月（95%CI，3.83 至 4.77 个月），中位无进展生存期（PFS）分别为 1.40 个月（95%CI，1.20 至 1.83 个月）、3.67 个月（95%CI，2.17 至 6.80 个月）和 3.20 个月（95%CI，2.37 至 4.53 个月）。阿帕替尼组与安慰剂组的 PFS（P<0.001）和 OS（P<0.001 和 P=0.0017）均有统计学显著差异。9 例患者有部分缓解（B 组 3 例，C 组 6 例）。毒性可耐受或可临床处理。最常见的 3 至 4 级不良事件为手足综合征和高血压。血液学毒性为中度，3 至 4 级血液学毒性罕见。
阿帕替尼可改善二线化疗失败的大量预处理的 mGC 患者的 PFS 和 OS。
