Second-line TKI after first-line immunotherapy-based treatment in advanced HCC: Reconstructed IPD meta-analysis

Area of Science:

• Hepatocellular Carcinoma (HCC) treatment sequencing
• Oncology drug efficacy analysis
• Immunotherapy and tyrosine-kinase inhibitor combinations

Background:

• Efficacy of second-line tyrosine-kinase inhibitors (TKIs) following first-line immunotherapy (IO) in advanced hepatocellular carcinoma (HCC) remains unclear.
• Limited data exists on comparative survival outcomes for TKIs used after IO progression.

Purpose of the Study:

• To evaluate the efficacy of second-line TKIs after first-line IO treatment in advanced HCC.
• To compare survival outcomes (overall survival and progression-free survival) of different TKIs in this setting.

Main Methods:

• Systematic literature search for studies on second-line TKIs after first-line IO in advanced HCC.
• Reconstruction of individual patient survival data from Kaplan-Meier curves.
• Analysis of overall survival (OS) and progression-free survival (PFS) using restricted mean survival time (RMST) and meta-regression.

Main Results:

• 1663 patients from 16 studies were analyzed, with most receiving atezolizumab-bevacizumab first-line.
• Lenvatinib and regorafenib demonstrated significantly longer 12-month OS and 6-month PFS compared to sorafenib.
• Survival outcomes were heterogeneous, with limitations due to the retrospective nature and potential confounding factors.

Conclusions:

• Second-line TKIs after IO therapy in advanced HCC show heterogeneous survival patterns.
• Lenvatinib and regorafenib appear to offer survival benefits over sorafenib in this context.
• Prospective studies are essential to establish optimal post-immunotherapy treatment sequencing strategies.