Anti-angiogenic therapies for gastric cancer

Tumor angiogenesis plays an important role in cancer cell proliferation and metastasis. In gastric cancer, among the numerous clinical trials investigating various anti-angiogenic therapies, such as antivascular endothelial growth factor (VEGF) or anti-VEGF receptor (VEGFR)-2 monoclonal antibodies, VEGF-Trap and VEGFR tyrosine kinase inhibitors, the anti-VEGFR-2 antibody ramucirumab was shown to prolong overall survival not only as a single agent but also in combination with paclitaxel as a second-line chemotherapy. Additionally, apatinib, a selective VEGFR-2 tyrosine kinase inhibitor, prolonged survival as a third-line or later treatment option in patients with advanced gastric cancer. Preliminary results of studies investigating ramucirumab plus immune checkpoint inhibitors in gastric cancer were encouraging, and further investigations are ongoing. In China, apatinib in combination with cytotoxic agents is being investigated for systemic chemotherapy or maintenance therapy as an earlier treatment option. The clinical activity in gastric cancer of the multikinase inhibitor regorafenib was suggested in a randomized phase II study. A global phase III trial comparing regorafenib with placebo is currently ongoing. Further studies of anti-angiogenic therapy combined with not only chemotherapy but also immune checkpoint inhibitors are also being pursued, providing hope for improved survival in patients with gastric cancer.