Real-World Evidence Favours Immunotherapy Over Lenvatinib in Advanced HCC- Hepatology Feb.26

Immune checkpoint inhibitor–based regimens have become central to the treatment of advanced hepatocellular carcinoma (HCC), but comparative effectiveness against tyrosine kinase inhibitors in real-world practice remains an important clinical question. This study used a target trial emulation approach to compare outcomes of first-line immunotherapy versus lenvatinib in patients with advanced HCC treated in routine clinical settings.

Using a large U.S. healthcare database, the investigators identified patients who received either immunotherapy-based combinations (atezolizumab plus bevacizumab or durvalumab plus tremelimumab) or lenvatinib as initial systemic therapy. By applying rigorous propensity score matching, the study aimed to minimize bias and approximate the conditions of a randomized trial. Overall survival was the primary outcome.

The analysis showed that immunotherapy was associated with longer overall survival compared with lenvatinib in the overall cohort. When specific regimens were examined, atezolizumab plus bevacizumab demonstrated a clear survival advantage over lenvatinib, while durvalumab plus tremelimumab showed a favorable trend that did not reach statistical significance, likely due to smaller sample size. Importantly, the benefit of immunotherapy was most pronounced in patients with viral hepatitis–related and alcohol-associated HCC, whereas no clear survival difference was observed in patients with metabolic dysfunction–associated steatotic liver disease.

These findings reinforce current guideline recommendations supporting immunotherapy as first-line treatment for advanced HCC and highlight the potential importance of disease etiology in treatment response. While observational in nature, this study provides strong real-world evidence that complements randomized trial data and supports immunotherapy as the preferred initial systemic therapy for most patients with advanced HCC.