Efficacy and toxicity of apatinib combined with or without chemotherapy for patients with advanced or metastatic chemotherapy-refractory gastric adenocarcinoma: A prospective clinical study

Apatinib (Jiangsu HengRui Medicine Co. Ltd), a vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor, has been proven to be safe and to significantly prolong survival in advanced chemotherapy-refractory gastric cancer. This study aimed to assess and compare the efficacy and safety of apatinib combined with chemotherapy with that of chemotherapy alone as second- or higher-line treatment in patients with advanced and metastatic gastric or those with metastatic gastroesophageal junction adenocarcinoma (mGC). Patients with chemotherapy-refractory mGC at Jiangsu Cancer Hospital & Research Institute were prospectively enrolled and assigned into 2 groups at a 2:1 ratio. The first group (combination group) comprised patients with combination treatment (apatinib + chemotherapy), while the second group comprised patients treated with chemotherapy alone (chemotherapy group). The dose of apatinib was 500 mg/d, and the chemotherapy regimens were based on fluoropyrimidine, platinum, and paclitaxel or irinotecan. The primary end points were progression-free survival (PFS). Between November 2014 and December 2016, 175 patients were enrolled. PFS was significantly improved in the combination group compared with that in the chemotherapy group (8.5 months [95% confidence interval [CI], 6.45–10.54] vs 7.0 months [95% CI, 5.12–8.88] P = .021; hazard ratio (HR): 0.645 [95% CI: 0.429–0.969] P = .035). The disease control rate (DCR) was also higher in the combination group than that in the chemotherapy group (58.4% vs 41.9%, P = .041). Moreover, the incidence of Grade 3 to 4 hand-foot syndrome, proteinuria, and hypertension was significantly different between the 2 groups. Combined therapy (P = .040) and metastatic sites <2 (P = .008) were the independent prognostic factors for disease progression. Compared with chemotherapy alone, the addition of apatinib to chemotherapy could better improve PFS and DCR with an acceptable safety profile for mGC refractory to 1 or more line of prior chemotherapy.