Recently, the 51st Annual Meeting of ASCO, the most prestigious academic feast in oncology, has come to an end. Although this year’s ASCO annual meeting in the field of gastrointestinal oncology did not have as amazing results announced as last year’s CALGB 80405 study, there were still many new studies that brought new insights to clinical practice from different perspectives, fully reflecting the theme of the meeting: “Insights and Innovations: Translating Data into Learning”. In this paper, we will only take stock of the important studies in gastric cancer among GI tract tumors. Molecular Targeting and Immunotherapy MET Monoclonal Antibodies for Primary Treatment of Advanced Gastric/Gastroesophageal Combined Carcinoma The results of two studies of MET inhibitors in gastric cancer were presented at this year’s ASCO Annual Meeting, one of which (RILOMET-1) was presented orally in a special session on gastrointestinal oncology, while the other (METGastric) was a poster session. center randomized controlled phase III clinical study enrolling 609 untreated patients with advanced human epidermal growth factor receptor 2-negative gastric/gastroesophageal junction cancer confirmed to be MET-positive by immunohistochemistry. Patients were randomized to the trial group [MET monoclonal antibody rilotumumab + ECX (epirubicin/cisplatin/capecitabine)] and the control group (placebo + ECX) with the primary study endpoint of overall survival (OS) period. It was found that instead of prolonging OS, the trial group had worse OS than the placebo group (9.6 months versus 11.5 months, HR=1.36, p=0.021) and a higher incidence of adverse events. The study was eventually terminated early in November 2014 because of more deaths in the trial group. Not coincidentally, another global multicenter phase III clinical study of MET monoclonal antibodies, METGastric, reached similar conclusions, and the addition of another MET monoclonal antibody, onartuzumab, to mFOLFOX6 did not prolong OS (11.0 months versus 11.3 months, HR=0.82, P=0.244), even in the MET high expression group (MET2+/3+) no survival benefit was seen. Grade 3 and 4 adverse reactions were significantly increased in the combination onartuzumab group, particularly neutropenia, thrombocytopenia, edema, and pulmonary embolism. Taken together, these findings suggest that the exploration of monoclonal antibodies targeting MET in gastric cancer has largely come to a halt. In contrast, small molecule tyrosine kinase inhibitors (TKI) targeting MET (e.g. AMG337) have emerged in preliminary clinical studies, and their exact efficacy needs to be confirmed by further studies. Anti-angiogenic multi-targeted TKI for refractory advanced gastric/gastroesophageal cancer The multi-targeted anti-angiogenic TKI regrafinib has been approved by the US Food and Drug Administration (FDA) for the treatment of drug-resistant advanced colorectal cancer (CRC). The results of a phase II study (INTEGRATE) of regefenib in advanced gastric cancer were presented in a special oral presentation session at this year’s ASCO Annual Meeting. The study randomized 152 patients with refractory advanced gastric/gastroesophageal union cancer in a 2:1 ratio and showed that regifenib significantly prolonged progression-free survival (PFS) compared to placebo (2.6 months versus 0.9 months, HR=0.40, p<0.0001). There was no significant prolongation of OS in the trial group (5.8 months versus 4.5 months, HR=0.74, P=0.11) because the study design allowed crossover from the placebo group to the regrafinib group after disease progression. The results of the subgroup analysis suggested that regrafinib was effective in prolonging the PFS period in patients from all geographic regions, and the prolongation of PFS period was particularly significant in Korean patients. Although the effectiveness of regrafinib in refractory gastric cancer still needs to be confirmed in phase III studies, the current findings suggest that regrafinib is likely to be another effective anti-angiogenic targeted agent for the treatment of advanced gastric cancer after ramucirumab. Anti-PD-1 immunotherapy in refractory advanced gastric cancer The results of a phase Ib study (KEYNOTE-012) of the anti-programmed death receptor-1 (PD-1) monoclonal antibody pembrolizumab for advanced gastric/gastroesophageal junction cancer were presented at the 2015 American Society of Clinical Oncology Gastrointestinal Oncology Symposium held earlier this year, and the results of this ASCO Annual Meeting presented updated data from this study in an oral presentation, as well as the relationship between the intensity of programmed death receptor-ligand 1 (PD-L1) expression and efficacy. The study enrolled 39 patients with PD-L1-positive refractory advanced gastric/gastroesophageal union cancer, all treated with pembrolizumab. The results showed a center-reviewed objective remission rate (ORR) of 22.2%, a PFS period of 1.9 months, and an OS period of 11.4 months (data are still immature and the upper 95% confidence interval has not yet been reached). The results of the exploratory analysis suggested that the intensity of PD-L1 expression in tumor cells and stroma was significantly correlated with OS stage (p=0.01). Another study from China analyzed the relationship between tumor infiltrating lymphocytes (TIL) and PD-L1 expression and prognosis in 398 Chinese gastric cancer patients, and the results showed that TIL density was significantly positively correlated with PD-L1 expression in tumor cells, but only TIL was an independent prognostic factor, and the difference between PD-L1 expression and prognosis was not statistically significant. From the above findings, it can be seen that anti-PD-1 immunotherapy has shown initial success in gastric cancer, but the beneficiary population is still unclear, and future studies should continue to explore biomarkers that can predict efficacy and enrich the dominant population under their guidance to proceed. Exploration of chemotherapy regimens based on pathological staging of enriched populations Chemotherapy for gastric cancer has not been groundbreaking in recent years, and there were no oral presentations on gastric cancer chemotherapy studies at this year's ASCO annual meeting. A randomized controlled phase III clinical study (DIGEST) evaluating the efficacy of the chemotherapeutic agent S-1 in advanced diffuse gastric cancer was presented in a poster session at the meeting. The study design was based on the results of a subgroup analysis of the previously conducted FLAGS study, in which the CS regimen (cisplatin + S-1) appeared to be superior to the CF regimen (cisplatin + 5-fluorouracil) in diffuse gastric cancer. 361 patients with initially treated advanced gastric cancer were randomized in the DIGEST study in a 2:1 ratio, and all had Lauren's staging of diffuse type. The primary endpoint of the study was the OS period, which was 7.5 months in the CS group and 6.6 months in the CF group (HR=0.99, P=0.9312), with no statistically significant difference. The difference in PFS period between the two groups was also not statistically significant, and the dose intensity and adverse effects were similar. the DIGEST study is another study of S-1 after the FLAGS study that failed in Western populations, despite population enrichment based on pathological typing. the different results of S-1 in different ethnic groups suggest that gastric cancer, as a highly heterogeneous disease, is difficult to achieve true population enrichment by relying on a single pathological feature. Molecular typing based on gene expression patterns is the development direction of individualized treatment. Laparoscopic versus open surgery for progressive gastric cancer The efficacy and safety of laparoscopic surgery for early gastric cancer have been recognized, but its application in progressive gastric cancer is still controversial. A prospective multicenter randomized controlled study from China (CLASS-01) was presented in a poster session at the ASCO Congress. The study was initiated by the Chinese Laparoscopic Gastrointestinal Surgery Study Group (CLASS) to compare the safety and efficacy of laparoscopic distal D2 radical surgery with conventional open surgery for locally progressive gastric cancer. A total of 607 patients were enrolled in the study and randomized to laparoscopic (LG) or open surgery (OG). To ensure the quality of the study, all participating surgeons were carefully selected and experienced, and the procedures were photographed and documented. The preliminary results published here showed that the differences in surgery-related complications and morbidity and mortality rates between the LG and OG groups were not statistically significant, suggesting that laparoscopic surgery performed by experienced surgeons for locally progressive gastric cancer is safe, with long-term survival data pending further follow-up results.