S1888 Helicobacter pylori Seropositivity Is Associated With Worse Outcomes Among Patients on Immunotherapy for Gastric Cancer

Introduction: Helicobacter pylori (Hp) is a known risk factor for gastric cancer. Hp virulence factors induce PD-1/L1 expression to promote infection and eventual tumorigenesis. Theoretically, Hp seropositivity should hinder the efficacy of immune checkpoint inhibitors (ICIs) used for cancer treatment, particularly anti-PD1/L1 agents, leading to worse patient outcomes. Animal models have supported this conclusion in various tumors. This phenomenon has yet to be studied in a human population or in gastric cancer, however. For this reason, we aim to explore the effect of Hp serostatus on survival in patients with gastric cancer. Methods: This was a single-center, retrospective chart review of all patients diagnosed with gastric adenocarcinoma. Patients with a different cancer subtype (lymphoma, neuroendocrine tumors, metastases, etc…) were excluded. Primary variables of interest included Hp serostatus (if diagnostics were negative or no testing, patient was considered Hp-) and treatment with ICIs. Other clinical information included patient demographics, gastric cancer histology, presence of other cancers, and vital status. Results: 2930 patients were included in the initial analysis. Two hundred and 6 patients (7.0%) received ICI, 196 (6.7%) had Hp infection, and 1037 (35.4%) had a mucinous subtype. Mucinous cancer subtypes were associated with improved survival (p < 0.05) at 3 and 5 years compared to non-mucinous, and at 10 years only among Hp+ patients (P = 0.013, vs. P = 0.120 for HP-). Subgroup analyses for patients who received ICI and those who did not showed that Hp positivity was significantly associated with worse survival at 3 years (OR: 2.0, P = 0.041) among patients on ICIs, but not for patients not receiving ICIs (P = 0.325). Conclusion: The link between Hp and ICI efficacy has been explored in animal studies, but in only 1 clinical study thus far. We found that Hp seropositivity may negatively impact the therapeutic effect of ICIs and was associated with worse survival at 3 years in this subgroup. Mucinous adenocarcinoma was associated with better survival at 3 and 5 years, with an additional survival benefit at 10 years only among Hp+ patients. Altogether, these findings suggest that Hp infection may be an obstacle to successful immunotherapy and may interact with cancer subtypes to differentially impact survival. Future studies are needed to validate the potential prognostic value of Hp seropositivity in gastric cancer (Figure 1, Table 1).Figure 1.: Cox Hazard Analysis of 3-year Survival for Helicobacter pylori Status among Patients on Immune Checkpoint Inhibitors. Table 1. - a) Multivariate Cox Hazard analysis for 3- and 5-year survival among patients on ICI; b) Multivariate Cox Hazard analysis for 10-year survival among patients with and without Hp a. Multivariate Cox Hazard analysis for 3- and 5-year survival among patients on ICI, n = 200 3-year survival 5-year survival Variable Hazard ratio P-value Hazard ratio P-value Age 0.9(0.9-0.9) 0.006* 0.9(0.9-0.9) 0.018* Hp + vs. Hp - 2.0(1.0-4.0) 0.041*1 1.5(0.8-2.6) 0.224 Mucinous vs. non-mucinous adenocarcinoma 0.4(0.2-0.9) 0.042* 0.5(0.2-0.9) 0.049* Race: Asian vs. non-Asian2 0.7(0.4-1.3) 0.239 - - Presence of other cancers (concurrent or preceding gastric cancer)2 1.4(0.7-2.8) 0.292 - - b. Multivariate Cox Hazard analysis for 10-year survival among patients with and without Hp Hp - n = 2734 Hp + n = 195 Variable Hazard ratio P-value Hazard ratio P-value Age 0.9(0.9-0.9) 0.000* 0.9(0.9-0.9) 0.006* Mucinous vs. non-mucinous adenocarcinoma 0.9(0.8-1.0) 0.120 0.5(0.2-0.8) 0.013* Receiving ICI vs. no ICI 1.8(1.4-2.3) 0.000* 2.2(1.2-4.2) 0.006* Abbreviations: ICI = immune checkpoint inhibitors, Hp = Helicobacter pylori.*Significant at the P < 0.05 level.1Running the same analysis for patients not on ICI, findings were similar except for Hp seropositivity, which was no longer significant (P = 0.325).2These variables were excluded from the analysis at 5-years given their lack of significance at the 3-year analysis.