Systemic therapy for advanced hepatocellular carcinoma with lung metastases
A 9 cm hepatocellular carcinoma (HCC) with metastatic lung nodules is managed as advanced HCC with systemic therapy rather than liver-directed locoregional therapy. [1]
In advanced HCC with preserved liver function (Child-Pugh A) and good performance status (ECOG 0–1), guideline-directed treatment is an immune checkpoint inhibitor–containing combination. [1]
Medication selection algorithm
Systemic therapy selection is based on liver function status and contraindications rather than tumor size or prognostic serum markers. [1]
Immune checkpoint inhibitor–based combinations are recommended when criteria are met: [1]
- PD-1 or PD-L1 inhibitor–containing regimens (with or without a VEGF-pathway agent) (examples include atezolizumab plus bevacizumab). [1]
Key evidence supporting immune checkpoint inhibitor combinations
The IMbrave150 phase 3 trial showed improved overall survival (hazard ratio [HR] 0.58) and improved progression-free survival (HR 0.59) for atezolizumab plus bevacizumab compared with sorafenib in unresectable HCC. [2]
Monotherapy versus combination therapy
Combination therapy with atezolizumab plus bevacizumab is preferred over sorafenib monotherapy in treatment-naïve unresectable or metastatic advanced HCC when eligible for guideline-recommended immune checkpoint inhibitor combinations. [1], [2]
After discontinuation of immune checkpoint inhibitor–based combinations due to progression or treatment-related adverse events, tyrosine kinase inhibitors can be considered in selected patients. [1]
Important clarifications and nuances
Neither prognostic nor predictive scores should be used to support clinical decision-making between embolic therapy and systemic therapy in appropriate clinical contexts. [1]
The choice of systemic therapy should not be influenced by HCC etiology. [1]
Locoregional therapy is not recommended as the primary strategy when extrahepatic metastatic disease is present. [1]
Treatment initiation thresholds
Immune checkpoint inhibitor–containing combinations are recommended for advanced HCC when all of the following are present: [1]
- Preserved liver function (Child-Pugh A). [1]
- ECOG performance status 0–1. [1]
- No contraindications to immune checkpoint inhibition. [1]
Common pitfalls to avoid
Systemic therapy should not be used routinely in patients with decompensated cirrhosis outside a prospective clinical trial. [1]
Treatment goals and response assessment
Tumor response in systemic therapy should be assessed primarily using RECIST v1.1 criteria. [1]
Overall survival remains the primary endpoint for randomized controlled trials in advanced HCC. [1]