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

Abstract

Background The use of immune checkpoint inhibitors in upper track gastrointestinal malignancies is a major and rapidly evolving field of research. As a result in the last 5 years a lot of data have emerged from randomized clinical trials and even more are expected in the future. Methods The aim of the study was to systematically review and examine in a pooled analysis all the data from randomized clinical studies on the use of immune checkpoint inhibitors compared to chemotherapy in the second line of treatment for advanced upper gastrointestinal cancers. Results Systematic literature search revealed five randomized, multicenter clinical trials, comparing the use of immunotherapy against chemotherapy in the second-line treatment of upper gastrointestinal carcinoma. Overall a total of 2190 patients were randomized, 1096 of whom received immunotherapy and 1094 standard chemotherapy. In the overall population immunotherapy demonstrated an improved overall survival with a significant 16% lower risk of death compared to chemotherapy (HR 0.84, 95% CI 0.76 to 0.93, p 0.0004). The benefit of immunotherapy was even more prominent for patients with CPS score > 1 or > 10 and for those with squamous cell histology. In contrast, there was no survival benefit confirmed in patients with esophageal or G/GEJ adenocarcinoma (HR 0.99, 95% CI 0.85 to 1.15, p = 0.89). Also, a benefit of immunotherapy in progression free survival was only evident in patients CPS score > 10 (HR 0.71, 95% CI 0.56 to 0.89, p = 0.003), but not in the overall population (HR 1.06, 95% CI 0.79 to 1.42, p = 0.70). Conclusions The above findings highlight the benefit of second-line immunotherapy, but further investigation is needed in future studies to discover the patient populations that will benefit the most from such an approach.