What can real-world data teach us about treating patients with unresectable hepatocellular carcinoma?

Abstract

Introduction: Hepatocellular carcinoma (HCC) remains a major global health concern, as it is the most common primary liver cancer and the fourth leading cause of cancer-related mortality.

Areas covered: Immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm, offering promising survival outcomes. However, the controlled conditions of randomized clinical trials (RCTs) often fail to reflect real-world complexities, emphasizing the necessity for strong real-world evidence (RWE). RWE, in most cases derived from observational studies, provides critical insights into the effectiveness, safety, and tolerability of systemic therapies across diverse populations and settings. The authors searched MEDLINE, Ovid Embase, and Scopus for full-text published articles in any language from the inception to 30 June 2024.This review evaluates RWE on systemic therapies for advanced HCC, including tyrosine kinase inhibitors (TKIs) like sorafenib and lenvatinib, ICIs such as nivolumab and pembrolizumab, and combination therapies like atezolizumab/bevacizumab and durvalumab/tremelimumab.

Expert opinion: Studies reveal discrepancies in treatment efficacy and adverse event profiles between RCTs and routine clinical practice, underscoring the need for individualized treatment strategies. RWE highlights the influence of liver disease etiology, liver function, and tumor burden on treatment outcomes, guiding therapy selection.

Keywords: Hepatocellular carcinoma; ICIs; TKI; randomized controlled trials; real-world evidence; systemic therapy.