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.
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.
Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is now the fastest-growing cause of hepatocellular carcinoma (HCC). Because a substantial proportion of MASLD-related HCC develops before cirrhosis, better tools are needed to identify high-risk patients who...
Introduction: The HIMALAYA trial established durvalumab plus tremelimumab (STRIDE) as a first-line treatment for unresectable hepatocellular carcinoma (HCC). However, many real-world patients do not meet the strict eligibility criteria of clinical trials. This multicenter study...
Introduction: Prognosis in unresectable hepatocellular carcinoma (HCC) depends not only on tumor burden but also on liver function and nutritional status. This study evaluated the prognostic value of ALBI grade, EZ-ALBI grade, and sarcopenia in...
Introduction: Hepatocellular carcinoma (HCC) surveillance enables earlier diagnosis and improves survival. This largest UK multicenter study evaluated how patients are diagnosed in routine clinical practice and identified major gaps in the surveillance pathway. Why was...
Introduction: Selective internal radiation therapy (SIRT) using yttrium-90 (Y90) glass microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), but guideline recommendations remain inconsistent. This large prospective multicenter study evaluated the real-world effectiveness, safety,...
Introduction: Atezolizumab–bevacizumab (A/B) and durvalumab–tremelimumab (STRIDE) are preferred first-line treatments for advanced hepatocellular carcinoma (HCC). Because bevacizumab inhibits VEGF, concerns remain regarding bleeding and thromboembolic complications in patients with underlying cirrhosis and portal hypertension. Why...
We are pioneers in clinical intelligence, dedicated to helping gastroenterologists harness the power of artificial intelligence to drive precision, efficiency, and patient growth.