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.

Response to Yu and Fuhleret al

“…We thank Yu and Fuhler et al 1 for their interest and insightful comments regarding our recent study entitled 'Impact of Helicobacter Pylori Infection Status on Outcomes among Patients with Advanced Gastric Cancer Treated with Immune Checkpoint Inhibitors'. 2 We agree with the commenting authors that there is a diagnostic advantage to using multimodal testing to determine H. pylori infection status. However, due to our study's retrospective and observational design we did not have access to serum samples for dedicated antibody testing in this study and acknowledge this as a limitation.…”

“…We thank Yu and Fuhler et al 1 for their interest and insightful comments regarding our recent study entitled ‘Impact of Helicobacter Pylori Infection Status on Outcomes among Patients with Advanced Gastric Cancer Treated with Immune Checkpoint Inhibitors’. 2 …”

Bioactive peptides as alternative treatment for Helicobacter pylori infection

“…As previously noted, the majority of patients infected with H. pylori exhibit histologic gastritis, and the phenotype of this gastritis will influence the progression of symptoms [48][49][50]. Most of the patients have a mild gastritis phenotype that in general is asymptomatic and do not affect the acid secretion, 10 to 15% presents the duodenal ulcer phenotype that affects the secretory function with a higher production of gastrin and acid secretion, with disturbances in the inhibitory control of acid secretion leading to dyspeptic symptoms and/or duodenal ulcer, and less than 1% present the gastric cancer phenotype that culminates in a strong reduction or absence of acid secretion, leading to severe atrophic gastritis, intestinal metaplasia and gastric cancer [21,34,[51][52][53].…”

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

“…We have read with great interest the recent publication titled ‘Impact of Helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors’ by Magahis et al . 1 The study presents intriguing findings on the association between H. pylori infection status and the efficacy of immune checkpoint inhibitor (ICI) therapy in patients with advanced gastric cancer. We commend the authors for their contribution to this critical field of cancer research.…”