Systemic therapies for hepatocellular carcinoma: the present and the future

Area of Science:

• Hepatocellular carcinoma (HCC) research
• Oncology
• Medical treatment strategies

Background:

• Hepatocellular carcinoma is often diagnosed at an unresectable stage, limiting curative treatment options.
• Sorafenib was the sole first-line systemic therapy for unresectable HCC for over a decade.
• Lenvatinib demonstrated non-inferiority to sorafenib, offering an alternative first-line option.

Purpose of the Study:

• To review current evidence on systemic treatments for unresectable hepatocellular carcinoma.
• To explore future therapeutic strategies and challenges in managing unresectable HCC.
• To discuss the complexity of treatment decisions in patients with coexisting cirrhosis.

Main Methods:

• Systematic review of randomized controlled trials (RCTs) and clinical data.
• Analysis of first-line and second-line treatment efficacy for unresectable HCC.
• Evaluation of combination and sequential therapy approaches.

Main Results:

• Atezolizumab plus bevacizumab significantly improved overall survival and progression-free survival compared to sorafenib, establishing a new first-line standard.
• Regorafenib, cabozantinib, ramucirumab, nivolumab, and pembrolizumab are approved second-line treatments.
• Heterogeneous inclusion criteria in second-line RCTs and lack of direct comparisons hinder optimal agent selection.

Conclusions:

• The combination of atezolizumab and bevacizumab represents the current best-performing first-line treatment for unresectable HCC.
• Optimal sequencing and combination of second-line therapies for HCC require further investigation.
• Managing unresectable HCC is complex due to patient comorbidities like cirrhosis and liver decompensation risk.