Society: AGA

Background: Gut microbiota composition and diversity have been shown to influence the effectiveness of cancer immunotherapies. Recent evidence suggests that Heliobacter pylori infection may reduce the efficacy of immune checkpoint inhibitors (ICIs), but the validity of this association in large, diverse cohorts of gastric cancer patients is unknown. We aimed to determine the impact of H. pylori infection status on survival outcomes in individuals with gastric cancer undergoing ICI therapy.

Methods: This single-center, retrospective study included all individuals with primary gastric cancer undergoing treatment with ICIs and with documented H. pylori status at Memorial Sloan Kettering Cancer Center between July 2013 and October 2021. Positive H. pylori status was defined as a history of prior or active infection obtained via urea breath test, stool antigen test, and/or histopathology. Negative status was defined as explicitly negative infection testing; unknowns were excluded. The primary outcomes were progression-free survival (PFS; calculated as date of ICI initiation to date of first progression or death) and overall survival (OS; calculated as date of ICI initiation until death). Secondary outcomes included PFS and OS stratified by the usage of concurrent chemotherapy and demographic or histological differences between groups. Comprehensive reviews of medical charts, endoscopic procedures, and pathology reports were performed to identify H. pylori diagnoses and confirm outcomes.

Results: Of 215 ICI-treated gastric cancer patients meeting the inclusion criteria, 49 had a documented history of H. pylori infection prior to or upon cancer diagnosis and 166 had no documented infection. Compared to H. pylori negative patients, H. pylori positive individuals were more likely to be younger, non-white, and Hispanic while also demonstrating higher rates of non-cardia gastric cancers (73.5% vs. 41.6%, p<0.01) and intestinal-type histology (81.6% vs. 65.1%, p=0.08) (Table 1). The H. pylori positive group had significantly shorter PFS and OS than the negative group with an estimated median PFS of 3.2 months vs 6.8 months (HR 1.96, p<0.01) and an estimated median OS of 9.8 months vs 17.9 months (HR 1.54, p=0.02) (Figure 1). These findings persisted when excluding patients receiving concurrent chemotherapy. Multivariable analysis confirmed H. pylori status as an independent predictor of PFS (HR 1.89, p<0.01) and OS (HR 1.80, p<0.01).

Conclusions: In the largest study to date, H. pylori infection was found to be associated with shorter PFS and OS in gastric cancer patients undergoing ICI therapy. This suggests that H. pylori status may be a predictive marker of immune responsiveness. Future studies are needed to elucidate the specific mechanisms by which this immune regulation occurs and whether treatment of active infections would benefit immunotherapy outcomes.

Clinical, treatment, and outcome characteristics of gastric cancer (GC) patients treated with immune-checkpoint inhibitors (ICIs) by <i>Helicobacter pylori</i> infection status

Clinical, treatment, and outcome characteristics of gastric cancer (GC) patients treated with immune-checkpoint inhibitors (ICIs) by Helicobacter pylori infection status

<b>Figure 1.</b> Survival curves of progression-free survival (PFS) and overall survival (OS) in immune checkpoint inhibitor (ICI)-treated gastric cancer patients by <i>Helicobacter pylori </i>infection status: A, PFS in all patients receiving ICIs and concurrent chemotherapy; B, OS in all patients receiving ICIs and concurrent chemotherapy; C, PFS in patients only receiving ICIs; D, OS in patients only receiving ICIs

Figure 1. Survival curves of progression-free survival (PFS) and overall survival (OS) in immune checkpoint inhibitor (ICI)-treated gastric cancer patients by Helicobacter pylori infection status: A, PFS in all patients receiving ICIs and concurrent chemotherapy; B, OS in all patients receiving ICIs and concurrent chemotherapy; C, PFS in patients only receiving ICIs; D, OS in patients only receiving ICIs

Mark Schattner

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