Efficacy of immunotherapy in the first line treatment of advanced upper gastrointestinal tract malignancies: A pooled analysis of randomized clinical trials

Abstract

Background Upper gastrointestinal tract malignancies include cancers of the oesophagus, gastro-esophageal junction and stomach. For the management of advanced disease, chemotherapy remains the primary treatment option in the 1st line, but the use of immune checkpoint inhibitors is a rapidly evolving field of research. Methods The volume of data from randomized clinical trials of the use of immunotherapy in upper gastrointestinal malignancies is steadily increasing over the last five years. Thus, we performed a systematic literature search and a pooled analysis of the available data, including both published articles and conference abstracts to identify trials evaluating immune checkpoint inhibitors in the 1st line of upper gastrointestinal malignancies. Results We identified overall four randomized trials comparing the addition of immunotherapy vs. standard chemotherapy as 1st line regimen in upper gastrointestinal malignancies. A total of 3561 patients were randomized, 1781 of whom received combination chemotherapy with immunotherapy and 1780 received standardized chemotherapy. The addition of immune checkpoint inhibitors in the first-line has been shown to benefit overall survival of patients compared to chemotherapy alone (HR = 0.81, 95% CI 0.75-0.87, p <0.00001) with a reduction in the risk of death by 20%, and up to 30% in a population of patients with CPS> 5%. Progression free survival was also increased by the addition of immunotherapy to chemotherapy (HR = 0.75, 95% CI 0.69 -0.81, p <0.00001). Furthermore, the addition of immunotherapy to chemotherapy appears to lead to a 70% increase in objective responses compared to chemotherapy alone. Conclusions The above findings pose new bases for the management of advanced upper gastrointestinal malignancies in the 1st line, highlighting the important role of immunotherapy in combination with standard chemotherapy.