Impact ofHelicobacter pyloriinfection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors

Abstract

BackgroundGut microbiota composition can influence cancer immunotherapy response. Recent evidence suggestsHelicobacter pyloriinfection may reduce immune checkpoint inhibitor (ICI) efficacy in lung cancer and melanoma, but thorough characterization of this association in patients with gastric cancer is lacking. We aimed to determine the impact ofH. pylorion survival in this population.MethodsThis single-center, retrospective study included all ICI-treated individuals with metastatic gastric cancer and documentedH. pyloristatus at Memorial Sloan Kettering between July 2013 and October 2021.H. pylori-positive status was defined as history of infection obtained via breath test, stool antigen test, histopathology, and/or chart documentation. Negative status was defined as explicitly negative testing, histopathology, and/or chart documentation. Primary outcomes were progression-free survival (PFS) and overall survival (OS).ResultsOf 215 included patients, 49 had documented history ofH. pyloriinfection. Compared withH. pylori-negative patients, positive individuals tended to be younger, non-white, and Hispanic with non-cardia and intestinal-type gastric cancer.H. pylori-positive patients had significantly shorter median PFS (3.2 vs 6.8 months, HR 1.96, p<0.01) and OS (9.8 vs 17.9 months, HR 1.54, p=0.02). Multivariable analysis confirmedH. pyloriinfection as an independent predictor of PFS (HR 3.04, p<0.01) and OS (HR 2.24, p=0.01).ConclusionsIn this largest study of its kind,H. pyloriinfection was associated with inferior survival in ICI-treated patients with gastric cancer. This suggestsH. pyloristatus may be a prognostic marker of immune responsiveness. Future studies are needed to elucidate immunoregulatory mechanisms and whether treatment of active infections would improve immunotherapy outcomes.