Article type
Abstract
Background: Immunotherapy has significantly advanced the management of Hepatocellular Carcinoma (HCC), offering novel therapeutic alternatives for advanced stage patients. Nonetheless, these treatments, particularly immune checkpoint inhibitors, can provoke a distinctive array of immune-related adverse events (irAEs), impacting multiple organ systems and causing a wide range of toxicities. Severe irAEs can impair patient quality of life and necessitate adjustments in the treatment plan. Given that clinical trials may not fully capture all safety concerns, synthesizing data from both trials and real-world pharmacovigilance systems is crucial to understanding the complete toxicity profile of immunotherapy in HCC patients.
Objectives: This study aimed to conduct a thorough evaluation of the toxicity profile in HCC using multi-source medical data to provide a comprehensive reference for clinicians, optimize the risk-benefit ratio, and enhance the safety of immunotherapy in HCC treatment.
Methods: We systematically reviewed RCTs from PubMed, Embase, and Cochrane Library databases (January 2008-March 2024) focusing on ICI-based therapies for HCC. Primary outcomes included treatment-related AEs and irAEs graded 1-5 and 3-4. Secondary outcomes involved specific organ-related trAEs and irAEs. Network comparisons were performed across 16 treatments including ICI monotherapies (PD-1, PD-L1, and CTLA-4 inhibitors) and combinatorial regimens with two or three ICIs, as well as conventional treatments like Sorafenib, Lenvatinib, etc. Disproportionality analysis was done using FAERS database data to calculate reporting odds ratios and fatality proportions for different irAEs.
Results: Of the 22 included RCTs with 12,382 HCC patients, Regorafenib regimen had the highest risk of trAEs, followed by Apatinib and PD-L1+TKI regimens. For irAEs, the triple combination of PD-1+CTLA-4+TKI posed the highest risk of grade 1-5 irAEs, trailed by Apatinib and PD-1+TKI combinations. Sub-organ analysis revealed occurrences of enteritis, pneumonia, hepatitis, nephritis, myositis, thyroid dysfunctions, and pituitary inflammation. FAERS data consistently flagged signals for enteritis, pneumonia, hepatitis, and nephritis across all ICI regimens.
Conclusions: Despite some heterogeneity in clinical factors within the included RCTs and potential inaccuracies in FAERS data, our findings offer valuable insights to refine clinical strategies and design preventive measures for managing irAEs during ICI treatment for HCC patients.
Objectives: This study aimed to conduct a thorough evaluation of the toxicity profile in HCC using multi-source medical data to provide a comprehensive reference for clinicians, optimize the risk-benefit ratio, and enhance the safety of immunotherapy in HCC treatment.
Methods: We systematically reviewed RCTs from PubMed, Embase, and Cochrane Library databases (January 2008-March 2024) focusing on ICI-based therapies for HCC. Primary outcomes included treatment-related AEs and irAEs graded 1-5 and 3-4. Secondary outcomes involved specific organ-related trAEs and irAEs. Network comparisons were performed across 16 treatments including ICI monotherapies (PD-1, PD-L1, and CTLA-4 inhibitors) and combinatorial regimens with two or three ICIs, as well as conventional treatments like Sorafenib, Lenvatinib, etc. Disproportionality analysis was done using FAERS database data to calculate reporting odds ratios and fatality proportions for different irAEs.
Results: Of the 22 included RCTs with 12,382 HCC patients, Regorafenib regimen had the highest risk of trAEs, followed by Apatinib and PD-L1+TKI regimens. For irAEs, the triple combination of PD-1+CTLA-4+TKI posed the highest risk of grade 1-5 irAEs, trailed by Apatinib and PD-1+TKI combinations. Sub-organ analysis revealed occurrences of enteritis, pneumonia, hepatitis, nephritis, myositis, thyroid dysfunctions, and pituitary inflammation. FAERS data consistently flagged signals for enteritis, pneumonia, hepatitis, and nephritis across all ICI regimens.
Conclusions: Despite some heterogeneity in clinical factors within the included RCTs and potential inaccuracies in FAERS data, our findings offer valuable insights to refine clinical strategies and design preventive measures for managing irAEs during ICI treatment for HCC patients.