Background and aims: Immune checkpoint inhibitor–based combi- nations (ICIs), including atezolizumab–bevacizumab (AB), have improved outcomes in unresectable HCC, although responses remain heterogeneous. Concomitant medications may modulate treatment efficacy through systemic and tumor microenvironment– mediated effects. Inhibition of the renin–angiotensin system (RAS) has been shown to potentiate the effects of immunotherapy in different solid cancers, acting on angiogenesis, fibrosis, and immune regulation. Nonetheless, the clinical impact of RAS inhibition in patients with HCC receiving ICIs remains controversial. Method: We conducted a retrospective multicenter analysis of the national ARTE cohort, which includes patients with unresectable HCC treated with A + B, comparing those receiving therapy with angio- tensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) at treatment initiation with those not exposed. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were first evaluated using Kaplan–Meier analyses, univariate and multi- variate Cox and logistic regression models. Confounding variables were then addressed by propensity score subclassification based on relevant clinical, hepatic, and tumor-related variables, and survival outcomes were subsequently re-assessed. Results: A total of 538 patients were analyzed. In multivariate analyses, ACEi/ARB use was associated with worse OS (HR 1.29, 95% CI 1.00–1.66; p = 0.05) and a trend toward reduced DCR (OR 0.63, 95% CI 0.39–1.02). No associations were observed for PFS or ORR. After propensity score adjustment, patients receiving ACEi/ARB therapy (n = 182) had a numerically shorter median OS (17.0 vs 19.4 months) compared with non-users (n = 325), although this difference was not significant ( p = 0.36). Conclusion: In a large multicenter cohort of HCC patients treated with AB, concomitant ACEi/ARB therapy did not improve outcomes and was associated with a trend towards of poorer survival.
FRI-381 Inhibition of the renin–angiotensin system does not improve the outcomes of hepatocellular carcinoma treated with atezolizumab–bevacizumab
Alfredo Vozza;
2026-01-01
Abstract
Background and aims: Immune checkpoint inhibitor–based combi- nations (ICIs), including atezolizumab–bevacizumab (AB), have improved outcomes in unresectable HCC, although responses remain heterogeneous. Concomitant medications may modulate treatment efficacy through systemic and tumor microenvironment– mediated effects. Inhibition of the renin–angiotensin system (RAS) has been shown to potentiate the effects of immunotherapy in different solid cancers, acting on angiogenesis, fibrosis, and immune regulation. Nonetheless, the clinical impact of RAS inhibition in patients with HCC receiving ICIs remains controversial. Method: We conducted a retrospective multicenter analysis of the national ARTE cohort, which includes patients with unresectable HCC treated with A + B, comparing those receiving therapy with angio- tensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) at treatment initiation with those not exposed. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were first evaluated using Kaplan–Meier analyses, univariate and multi- variate Cox and logistic regression models. Confounding variables were then addressed by propensity score subclassification based on relevant clinical, hepatic, and tumor-related variables, and survival outcomes were subsequently re-assessed. Results: A total of 538 patients were analyzed. In multivariate analyses, ACEi/ARB use was associated with worse OS (HR 1.29, 95% CI 1.00–1.66; p = 0.05) and a trend toward reduced DCR (OR 0.63, 95% CI 0.39–1.02). No associations were observed for PFS or ORR. After propensity score adjustment, patients receiving ACEi/ARB therapy (n = 182) had a numerically shorter median OS (17.0 vs 19.4 months) compared with non-users (n = 325), although this difference was not significant ( p = 0.36). Conclusion: In a large multicenter cohort of HCC patients treated with AB, concomitant ACEi/ARB therapy did not improve outcomes and was associated with a trend towards of poorer survival.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
