A randomized, double-blind, multicenter, phase II, three-arm, placebo-control study of apatinib as third-line treatment in patients with metastatic gastric carcinoma.

4019 Background: Apatinib at a daily dose of 850mg was tolerable from our phase I study. The objective of this study was to evaluate the efficacy and safety of apatinib in patients with advanced or metastatic gastric cancer after failure of two lines of chemotherapy. Methods: Inclusion criteria were ECOG performance status ≤ 1, measurable disease and adequate organ functions. Patients were randomized to the placebo (A), 850mg qd (B), and 425mg bid (C) arm. Study treatment was continued as a 28-day cycle until progression or intolerable toxicity. Tumor assessments were performed after cycle 2, 3, and then every 2 cycle thereafter. The primary endpoint was progression-free survival (PFS). The secondary endpoints were disease-free control rate (DCR), objective response rate (ORR), and overall survival (OS). All adverse events were reported using CTCAE v3.0). COX analysis method was used. Results: 141 patients were enrolled. Results were presented in the table. Treatment-related toxicities of each arm was 8 (16.67%),13 (27.66%), 13 (50%), respectively, P=0.0021. The most common adverse events were hypertension and hand-foot syndrome. Conclusions: Apatinib once daily or twice daily has been shown to be active against gastric cancer with manageable safety profile. n PFS (M) Hazard ratio (95%CI) P Arm A 48 1.40 B vs A 0.353 (0.216, 0.578) <0.0001 B 47 3.43 C vs A 0.367 (0.224, 0.603) <0.0001 C 46 3.43 C vs B 0.997 (0.589, 1.689) 0.9909 OS(M) A 48 2.50 B vs A 0.525 (0.326, 0.845) 0.0080 B 47 4.83 C vs A 0.585 (0.363, 0.942) 0.0273 C 46 4.30 C vs B 1.191 (0.724, 1.961) 0.4908 ORR Arm % 95%CI Rate variance (95%CI) A 0.00 (0.0, 7.4) % B vs A (-0.61, 13.37) % B 6.38 (1.3, 17.5) % C vs A (3.31, 22.77) % C 13.04 (4.9, 26.3) % C vs B (-5.32, 18.64) % DCR Arm % 95%CI Rate variance (95%CI) A 10.42 (3.5, 22.7) % B vs A (15.56, 48.70) % B 42.55 (28.3, 57.8) % C vs A (12.17, 45.25) % C 39.13 (25.1, 54.6) % C vs B (-23.39, 16.55) %