Safety of Immune-Targeted Therapy in Patients with Hepatocellular Carcinoma in the Real-World.

BACKGROUND: Combining immunotherapy with targeted therapy represents a promising trajectory for cancer treatment; however, safety profiles remain insufficient. This study aimed to characterize adverse events associated with immune-targeted regimens in hepatocellular carcinoma (HCC).

METHODS: This study used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) to detect signals of adverse events based on data from FDA Adverse Event Reporting System.

RESULTS: Signals of fulminant type-1 diabetes mellitus (ROR = 13.3, PRR = 13.2, IC = 3.7), myositis (8.5, 8.3, 3.1), encephalitis (8.4, 8.3, 3.0), and myocarditis (7.3, 7.2, 2.8) were identified in atezolizumab+bevacizumab. Immune-mediated hepatitis (5.6, 5.1, 2.4), hepatic encephalopathy (3.3, 3.0, 1.6), and uppergastrointestinal haemorrhage (4.3, 4.2, 2.1) were associated with pembrolizumab+lenvatinib. Signals of gastrointestinal haemorrhage (5.1, 4.8, 2.3) and malignant neoplasm progression (2.9, 2.7, 1.4) were in patients using atezolizumab+cabozantinib.

CONCLUSION: This study delineated distinct profiles of adverse events associated with immunotargeted therapies, which serves as a critical reference for risk assessment and therapeutic selection. Though atezolizumab plus bevacizumab is recommended as first-line treatment for advanced HCC, potential severe immune-mediated adverse events affecting multiple organs suggested the importance of clinical vigilance. Extrapolation of pembrolizumab+lenvatinib and atezolizumab+cabozantinib from other cancers to HCC warrants caution in consideration of the associated bleeding risks and hepatic complications.