Effect of Vonoprazan, potassium-competitive acid blocker, on Atezolizumab plus Bevacizumab efficacy in patients with hepatocellular carcinoma: a multicenter retrospective study.

[BACKGROUND] Proton pump inhibitors (PPIs) have received considerable attention as inducers of gut dysbiosis through gastric acid suppression. PPI-induced gut dysbiosis is associated with a poor prognosis in patients with non-small cell lung cancer and urothelial cancer treated with immune checkpoint inhibitors (ICIs), but not in those with hepatocellular carcinoma (HCC). Although vonoprazan, which showed more powerful acid suppression than PPIs, tended to decrease efficacy in non-small cell lung cancer and urothelial cancer, its effect on ICIs therapy for HCC remains unknown and was evaluated in this study.

[METHODS] This multicenter retrospective study included patients aged ≥ 18 years with HCC who received atezolizumab plus bevacizumab (Atz/Bev) between September 2020 and December 2023 at five hospitals. The primary and secondary endpoints were differences in progression-free survival (PFS) and overall survival (OS), respectively.

[RESULTS] Of the 354 eligible patients, 115 received PPIs, 55 received vonoprazan, and 184 received neither vonoprazan nor PPIs (non-gastric acid suppression [GAS] group). In the multivariate analysis, compared to vonoprazan group, there were no significant differences in the PFS of the PPI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.73-1.53; P = 0.77) and non-GAS groups (HR, 0.93; 95% CI, 0.65-1.32; P = 0.67). Similarly, there were no significant differences in the OS of PPI (HR, 0.94; 95% CI, 0.59-1.48; P = 0.78) and non-GAS groups (HR, 0.75; 95% CI, 0.48-1.17; P = 0.20).

[CONCLUSION] Vonoprazan was not associated with worse PFS and OS in patients with HCC treated with Atz/Bev than in those who did not receive PPIs and neither.