Apatinib for Chemotherapy-Refractory Advanced Metastatic Gastric Cancer: Results From a Randomized, Placebo-Controlled, Parallel-Arm, Phase II Trial

作者：Jin Li, Shukui Qin, Jianming Xu, Weijian Guo, Jianping Xiong, Yuxian Bai, Guoping Sun, Yan Yang, Liwei Wang, Nong Xu, Ying Cheng, Zhehai Wang, Leizhen Zheng, Min Tao, Xiaodong Zhu, Dongmei Ji, Xin Liu, Hao Yu · 发表于：Journal of Clinical Oncology · 年份：2013 · DOI：10.1200/jco.2013.48.8585 · 被引用次数：559 · 研究领域：Gastric Cancer Management and Outcomes、Colorectal Cancer Treatments and Studies、Advanced Breast Cancer Therapies

PURPOSE: 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 AND METHODS: 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). RESULTS: 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 tox...