Heterogeneity in adverse events related to Atezolizumab-Bevacizumab for hepatocellular carcinoma reported in real-life studies

Highlights:•Systematic review analyzed 30 studies with 3867 HCC patients treated with atezolizumab-bevacizumab.•High variability in adverse events (AEs) reporting across studies available in literature.•Severe AEs like bleeding, thrombosis, and perforation are often underreported.•Need for standardized and thorough AE reporting in clinical practice.AbstractBackground & AimsThe aim of this study was to evaluate the incidence of adverse events (AEs) in patients with hepatocellular carcinoma (HCC) treated with atezolizumab-bevacizumab in literature.MethodsIn this systematic review and meta-analysis, we searched on Pubmed from 2020 to 2023 using "Atezolizumab/Bevacizumab", "HCC" and "Adverse events" and included original studies reporting percentages of AEs in patients with HCC receiving atezolizumab-bevacizumab. We summarized the incidence of adverse events and performed a meta-analysis in order to evaluate the incidence of AE reported in the literature.ResultsA total of 30 studies (3867 patients) were included. The analysis revealed heterogeneity in AEs reporting, with arterial hypertension, proteinuria, and fatigue being the most frequently reported AEs whereas incidence of bleeding was reported in 66.7% of the studies and rare immune-related adverse events was reported in 26.7% of the studies. The meta-analysis revealed pooled incidence rates of 79% for any grade AEs, 56% for grade 1/2, and 30% for grade≥3. While the pooled rates of hypertension, anorexia, bleeding, pruritus, rash, and thyroid dysfunction were similar to those reported in the IMbrave150 trial, higher rates were observed in literature for proteinuria, fatigue, ALT and AST elevation and gastrointestinal perforation. For grade≥3 AEs, the percentages were consistent with the IMbrave150 trial, except for lower incidences of arterial hypertension and thrombosis in literature. The exposure-adjusted incidence rates for proteinuria (55.7%), hypertension (45.3%) and fatigue (33.6%) were high. Heterogeneity was observed in the analysis of AEs across articles within the same cohorts of patients.ConclusionWe observed a significant variability in AEs reporting for atezolizumab-bevacizumab treatment in HCC in literature, underscoring the need for standardized reporting practices.Impact and ImplicationsConsidering the demonstrated safety of atezolizumab-bevacizumab in randomized controlled trials, this meta-analysis offers valuable insights into reported occurrences of adverse events. Our study highlights significant heterogeneity among studies, underscoring the need to improve adverse event recording. Understanding the incidence and severity of treatment-related adverse events beyond clinical trial is essential for prompt intervention and may help preventing treatment discontinuation and complications, potentially leading to better outcomes without significantly compromising quality of life due to adverse events.