Abstract
Gastric cancer (GC) remains a public health problem, being the fifth most common cancer worldwide. In the western countries, the majority of patients present with advanced disease. Additionally, 65 to 75% of patients treated with curative intent will relapse and develop systemic disease. In metastatic disease, systemic treatment still represents the state of the art, with less than a year of median overall survival. The new molecular classification of GC was published in 2014, identifying four distinct major subtypes of gastric cancer, and has encouraged the investigation of new and more personalized treatment strategies. This paper will review the current evidence of immunotherapy in advanced gastric cancer.
Highlights
Gastric cancer (GC) is the 5th most common cancer diagnosed worldwide, and it represents one of the major causes of malignant disease morbidity and mortality, with almost 107,000 deaths in Europe in 2012 [1, 2].The majority of the patients are diagnosed with locally advanced disease not suitable for surgery or metastatic disease
A phase II trial evaluated the efficacy of ipilimumab immediately following 1st line chemotherapy in unresectable or metastatic adenocarcinoma of the gastric and gastroesophageal junction (GEJ) compared with best supportive care (BSC)
In a phase I trial, atezolizumab was administered as a single agent to patients with locally advanced or metastatic solid tumours or hematologic malignancies, and 175 patients were evaluated by RECIST v1.1 and confirmed that complete and partial responses were observed in 18% of patients with all tumour types, 21% in non-smallcell lung cancer (NSCLC), 26% in melanoma, 13% in renal cell carcinoma, and 13% of patients with other tumours including colorectal cancer, gastric cancer, and head and neck squamous cell carcinoma
Summary
GC is the 5th most common cancer diagnosed worldwide, and it represents one of the major causes of malignant disease morbidity and mortality, with almost 107,000 deaths in Europe in 2012 [1, 2]. Ramucirumab, a vascular endothelial growth factor receptor (VEGFR-2) antibody, was the first biological treatment given as a single drug or in combination with paclitaxel in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma progressing after first-line chemotherapy that demonstrated survival benefits in two randomized trials [7,8,9,10,11]. MSI tumours seem to occur in 15–30% of GC and are related more commonly with female gender, older patients, and intestinal histology and tumours arising from the distal stomach This category of gastric cancer is characterized by increased lymphocytic infiltrate, which may reflects activation of T-cells against tumour antigens and genomic changes in tumour cells that are linked to PD-L1 expression, indicating a potential role for immunotherapy [13]. Both MSI and EBV positive GCs have a high somatic mutational burden which is a feature that has been associated with response to immunotherapy
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