| Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide. The prognosis of patients with advance gastric cancer (AGC) has been much improved during the past decades, however, still remains poor.There has been a modest improvement of cytotoxic chemotherapy of AGC. Newer agents with better safety profile and convenience were developed, and more patients are receiving 2nd-line or even 3rd-line chemotherapy with prolongation of overall survival. With cytotoxic chemotherapy alone, median survival of these patients is approximately 1 year at this time.Molecular targeted agents have been actively tested in AGC during the past decade. At this time, only 2 classes of agents have been shown to be effective. One is trastuzumab, a humanized anti-HER2 antibody, which is effective in HER2-positive AGC. ToGA trial clearly demonstrated that chemotherapy plus trastuzumab is more effective than chemotherapy alone. Median survival of patients with HER2 overexpression (IHC 2+ or 3+) was 16.0 months. The other is anti-VEGFR antibody or tyrosine kinase inhibitor. Two large phase III studies have shown that ramucirumab, a humanized VEGFR2 antibody, alone or in combination with paclitaxel, was effective as the 2nd-line treatment of AGC. In the Chinese phase III study, apatinib, a selective inhibitor of VEGFR2, prolonged overall survival of patients as the 3rd+-line treatment of AGC.Recently, immune check-point inhibitors are tested in patients with AGC. Ipilimumab, an anti-CTLA-4 antibody, was tested in a randomized phase II study as the maintenance therapy after 1st-line chemotherapy, however, the results was negative. Pembrolizumab, an anti-PD-1 antibody, was tested in 39 patients with PD-L1-positive AGC. Objective response rate by central review was 22.2%, and median overall survival was 11.4 months. Avelumab, an anti-PD-L1 antibody, was tested as the 2nd-line or maintenance therapy in all-comers. Sixty-two patients were treated in the 2nd-line setting, and objective response rate was 9.7%. Very recently, the results of phase III study, in which nivoulmab was compared to placebo as the 3rd+-line treatment, were presented. Overall survival was prolonged by 1.18 months with a hazard ratio of 0.63 (5.32 months and 4.14 months, respectively). At this time, a number of phase III trials of anti-PD-1 or anti-PD-L1 antibodies are ongoing, either as monotherapy or in combination with chemotherapy. |
