Gastric cancer is the fifth most common malignancy worldwide and one of the main causes of cancer-related death. While surgical treatment is the only curative option for early disease, many have inoperable or advanced disease at diagnosis. Treatment in this case would be a combination of chemotherapy and immunotherapy. Gastro-esophageal (GEJ) and gastric cancer (GC) genetic profiling with current molecular diagnostic techniques has significantly changed the therapeutic landscape in advanced cancers. The identification of key players in GEJ and GC survival and proliferation, such as human epidermal growth factor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1), has allowed for the individualization of advanced cancer treatment and significant improvement in overall survival and progression-free survival of patients. This review comprehensively examines the current and emerging role of monoclonal antibody-based first-line treatments in advanced GEJ and GC. We explore the impact of monoclonal antibodies targeting HER2, VEGF, PD-1/PD-L1, and Claudin 18.2 (CLDN18.2) on the first-line treatment landscape by talking about key clinical trials. This review emphasizes the importance of biomarker testing for optimal treatment selection and provides practical recommendations based on ASCO guidelines.

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples (p ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy (p = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; p = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; p = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; p = 0.04) or ≥5% (HR 0.19; p = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; p = 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes.