Gastric cancer has a high incidence and mortality rate worldwide. Epidemiological, clinical, and molecular features significantly impact patient outcomes. In regions lacking a national gastric cancer registry, hospital-based registries can provide crucial data that may aid in planning therapeutic strategies for the disease. A retrospective observational cohort design was carried out in European Union (EU) and Latin American (LATAM) countries participating in the LEGACy project. Survival estimates were determined using actuarial Kaplan–Meier curves. Comparison was carried out with the log-rank test, and differences were considered statistically significant for P values ≤0.05. A total of 689 patients diagnosed with gastric cancer from November 2018 to November 2019 were included. Both cohorts had the body as the most common site reported (34.4% for EU and 51% for LATAM). The most used method for staging was computed tomography for both cohorts, although 6.9% of the LATAM population had positron emission tomography/computed tomography instead. Intestinal histological subtype was the most common (41.9% and 46.3% reported by EU and LATAM), while diffuse subtype was 44.9% for the LATAM and 21.3% for the EU population. Among patients tested for human epidermal growth factor receptor 2 (HER2), 12.5% were positive in the EU cohort and 13.8% in the LATAM cohort. For both cohorts, the most common site of human epidermal growth factor receptor 2 positivity was the gastroesophageal junction. Systemic treatment with curative intention was indicated in 50.7% in the EU cohort and 46.4% of the LATAM cohort. The most frequent scheme indicated for both the localized and the advanced setting was platinum-based (42.6% and 84.8% for EU and LATAM). Considering both cohorts, only 14.4% of the patients received second-line treatment, and 3% received a third-line treatment. After using Cox regression analysis, no difference in overall survival was reported, with a median of 10.9 months. Despite the limitations of hospital-based registry analysis, our study has provided valuable insights into clinical characteristics and treatment approaches of EU and LATAM populations.

Purpose: Immune checkpoint inhibitors combined with chemotherapy have provided successful results in patients with gastric and gastroesophageal junction (G/GEJ) cancers in the metastatic setting. Similar strategies have been explored in earlier stages. In this study, we present the final results of the phase II MONEO trial, which evaluated the addition of avelumab to neoadjuvant chemotherapy. Patients and Methods: Patients with untreated, resectable G/GEJ adenocarcinoma received neoadjuvant treatment with four cycles of avelumab plus the FLOT4 regimen, followed by surgery. Upon postoperative recovery, patients underwent four additional adjuvant cycles of the same combination, followed by avelumab monotherapy for up to 1 year. The primary endpoint was pathologic complete response rate. Sequential flow cytometry and cytokine determination were performed in peripheral blood, along with multiplex tissue immunofluorescence and RNA sequencing in tumor specimens. Results: Forty patients were enrolled, achieving a pathologic complete response rate of 21.1% (95% confidence interval, 10.0–37.0). The major pathologic response rate was 28.9%, more pronounced in patients with tumors expressing PD-L1 before treatment as measured by the combined positive score (cutoff, 10; 33.3% vs. 21.1%). The results propose several potential biomarkers considering tumor immune infiltrate, circulating immune cells, and cytokines. Eighty percent of patients experienced treatment-related grade ≥3 adverse events. Conclusions: The combination of avelumab plus the FLOT4 regimen showed relatively modest efficacy in resectable G/GEJ adenocarcinoma. Better results were observed in PD-L1 combined positive score ≥10% tumors. Exploratory biomarker analyses provide insights that may help to identify candidates most likely to benefit from chemoimmunotherapy as a neoadjuvant treatment.

Gastric and gastro-oesophageal junction cancer (GC) represent a global healthcare problem being the fifth most common tumour type and the fourth cause of cancer mortality. Extremely poor median survival of approximately 10 months is normally reported within advanced GC patients, mainly secondary to two factors, i.e., the fragility of these patients and the aggressiveness of this disease. In this context, the correct treatment of GC patients requires not only a multidisciplinary team with special attention to palliative and nutritional care but also a close follow-up with regular monitoring of disease symptoms and tumour evaluation. Sequential treatment lines with few toxic adverse events have emerged as the best therapeutic approach, and a third line of therapy could further improve survival and quality of life of GC patients. Chemotherapy, immunotherapy, and targeted agents -when indicated- constitute the treatment armamentarium of these patients. In this review, we discuss treatment options in the refractory setting as well as novel approaches to overcome the poor prognosis of GC.

Background: Gastric cancer (GC) patients from European (EU) and especially Latin American (LATAM) countries are underrepresented in previous large-scale multi-omic studies that have identified clinically relevant subgroups. The LEGACY study aimed to profile the molecular and immunological features of GCs from EU and LATAM countries. Methods: Tumor biopsies from 95 EU and 56 LATAM GCs were profiled with immunohistochemistry (CD3, CD8, FOXP3, PD-L1, MSI and HER2), Nanostring mRNA expression analyses, and microbiome sequencing. Results: Immune profiling identified four distinct immune clusters: a T cell dominant cluster with enriched activation pathways, a macrophage dominant cluster and an immune excluded microenvironment which were equally distributed among the countries. A fourth cluster of mostly Mexican patients consisted of excessive T cell numbers accompanied by enhanced cytokine signaling in absence of enhanced antigen presentation and cytotoxicity signatures and a strong association with H. pylori infection. Discussion: Both EU and LATAM countries have GCs with a T cell inflamed microenvironment that might benefit from checkpoint inhibition. We identified a highly inflamed GC subgroup that lacked antigen presentation and cytotoxicity associated with H. pylori CagA-positive strains, suggesting their contribution to tumor immune tolerance. Future studies are needed to unravel whether these cancers benefit from immunotherapy as well.

Supplementary Figure 1. Study flowchart.