Comparative safety profiles of atezolizumab-bevacizumab vs tyrosine kinase inhibitors in advanced hepatocellular carcinoma: A FAERS-based study.

Abstract

568 Background: Atezolizumab–bevacizumab (Atezo-Bev) has replaced tyrosine kinase inhibitors (TKIs) as the preferred first-line therapy for advanced HCC, but underlying cirrhosis or uncontrolled portal hypertension (PHTN) raise concerns for complications. Clinical trials underrepresent these high-risk patients, and comparative real-world safety data between these regimens remain limited. Post-marketing pharmacovigilance is needed to guide safer treatment selection. Methods: We conducted a retrospective study using Federal Adverse Event Reporting System (FAERS) data from Q1 2020 to Q1 2025. Reports involving Atezo-Bev and TKIs (sorafenib, lenvatinib, cabozantinib, regorafenib) were identified by drug name string-matching in patients with HCC and aggregated at the patient level. Events studied included variceal bleed, ascites, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), PHTN, upper gastrointestinal bleed (UGIB), splanchnic thrombosis (SVT), portal vein thrombosis (PVT), neutropenia, hepatotoxicity, colitis, pneumonitis, hypothyroidism, immune-related adverse events (irAEs), and outcomes (death, hospitalization). Disproportionality was assessed using proportional reporting ratios (PRR) and reporting odds ratios (ROR) with 95% confidence intervals (CI) for Atezo-Bev compared to TKIs, with TKIs serving as the reference group. Statistical significance was set at p<0.05. Results: A total of 9,450 adverse events (AEs) involving Atezo-Bev and 9,526 involving TKIs were identified. The majority occurred in patients aged 50–89 years. Atezo-Bev was linked to portal hypertension complications and mortality, while TKIs were associated with irAEs and hospitalization. Table 1 summarizes PRR and ROR values for key events. Conclusions: These findings reveal distinct safety trade-offs between Atezo-Bev and TKIs, highlighting the importance of individualized treatment in advanced HCC and the value of pharmacovigilance in complementing trial evidence. AEs and outcomes with PRR and ROR. AE/ outcome Atezo-Bev (%) TKI (%) PRR ROR 95% CI P value Variceal bleed 2.25 0.89 2.53 2.56 1.99-3.30 <0.0001 UGIB 1.99 1.80 1.11 1.11 0.90-1.37 0.33 Ascites 5.1 3.55 1.43 1.46 1.26-1.68 <0.0001 HE 1.92 5.02 0.38 0.37 0.31-0.44 <0.0001 SBP 0.17 0.03 5.38 5.38 1.57-18.48 0.007 PHTN 0.54 0.09 5.71 5.74 2.82-11.66 <0.0001 SVT 0.16 .05 3.02 3.03 1.10-8.33 0.03 PVT 0.76 0.4 1.96 1.97 1.32-2.93 0.0008 Hepatotoxicity 5.05 2.20 2.29 2.36 2.00-2.78 <0.0001 Neutropenia 0.73 0.41 1.78 1.79 1.21-2.65 0.004 Colitis 7.34 15.17 0.48 0.44 0.40-0.49 <0.0001 Pneumonitis 4.06 1.5 2.67 2.74 2.26-3.32 <0.0001 Hypothyroidism 4.52 2.46 1.84 1.88 1.60-2.21 <0.0001 irAEs 14.2 18.4 0.77 0.73 0.68-0.79 <0.0001 Death 29.6 20.3 1.46 1.65 1.54-1.77 <0.0001 Hospitalization 37.1 58.4 0.64 0.42 0.40-0.45 <0.0001