What is the role of Nivolumab (nivolumab) in treating metastatic hepatocellular carcinoma with lung metastasis and impaired liver function (Child-Turcotte-Pugh score of B)?

Nivolumab in Metastatic Hepatocellular Carcinoma with Child-Pugh B and Lung Metastasis

Nivolumab can be considered as a treatment option for this patient with metastatic hepatocellular carcinoma and Child-Pugh B liver function, but only with extreme caution and after careful risk-benefit assessment, as it represents one of the few viable systemic therapy options in this challenging population. 1

Evidence Supporting Nivolumab Use in Child-Pugh B

The 2024 ASCO guidelines explicitly recommend PD-1 or PD-L1 inhibitors (including nivolumab) as treatment options for Child-Pugh B patients with good performance status, though with a cautious approach. 1

Key efficacy data from CheckMate 040 Cohort 5:

• In 49 patients with Child-Pugh B7-B8 hepatocellular carcinoma treated with nivolumab, the objective response rate was 12% 1
• Median overall survival was 7.6 months 1
• The safety profile was comparable to Child-Pugh A patients 1, 2
• Disease control rate reached 55% 2

Critical Patient Selection Criteria

You must assess the following factors before initiating nivolumab: 1

• Underlying liver function - Limit to Child-Pugh B7-B8 only; Child-Pugh C is contraindicated 1, 2
• Bleeding risk - Evaluate for varices and coagulopathy 1
• Portal hypertension presence - Assess for ascites and hepatic encephalopathy 1
• Performance status - Must have good ECOG performance status (0-1) 1
• Tumor burden and major vascular invasion - Consider extent of disease 1

Safety Profile and Monitoring

Treatment-related adverse events occur at similar rates to Child-Pugh A patients: 1

• Grade 3-4 treatment-related adverse events occurred in 28% of Child-Pugh B patients in retrospective series 3
• Immune-related adverse events occurred in approximately 50% of patients 3
• Steroid requirement was needed in 28% of patients 3
• Treatment discontinuation due to adverse events occurred in 22% 3

The most common grade 3-4 treatment-related adverse events include: 2

• Hypertransaminasemia
• Amylase elevation
• AST elevation

Dosing and Administration

Nivolumab should be administered at 240 mg intravenously every 2 weeks until disease progression or unacceptable toxicity. 2 This dosing was established in the CheckMate 040 trial and showed tolerability in Child-Pugh B7-B8 patients. 2

Critical Limitations and Contraindications

Important restrictions that apply to this patient: 4

• All second-line agents (regorafenib, cabozantinib, ramucirumab, pembrolizumab after nivolumab failure) require Child-Pugh A and are NOT recommended for Child-Pugh B 4
• Atezolizumab plus bevacizumab is NOT recommended for Child-Pugh B patients due to bleeding concerns with bevacizumab and lack of clinical trial data 1, 4
• Durvalumab plus tremelimumab has no data in Child-Pugh B patients 4

Alternative First-Line Options

If nivolumab is not suitable, sorafenib remains the primary alternative: 4

• Sorafenib 400 mg orally twice daily is the standard treatment for Child-Pugh B7 patients with good performance status 4
• This recommendation has B1 level evidence from multiple international guidelines 4
• Lenvatinib has limited data in Child-Pugh B and higher adverse event rates 1, 4

Management of Lung Metastases

For symptomatic lung metastases, external beam radiation therapy should be considered for palliation: 4

• This has B1 level evidence for symptom control 4
• Radiotherapy is particularly useful for symptomatic metastases 1, 4

Shared Decision-Making Requirements

The 2024 ASCO guidelines emphasize that treatment decisions must involve extensive shared decision-making with the patient given: 1

• Very low quality of evidence (GRADE: Very Low) 1
• Weak strength of recommendation 1
• Modest expectations for clinical benefit 1
• Risk of life-threatening immune-related toxicities 1

A multidisciplinary team including hepatologists, surgeons, radiologists, pathologists, and oncologists should make treatment decisions whenever possible. 1

Common Pitfalls to Avoid

Do not use nivolumab if: 1, 4

• Child-Pugh score is C - systemic therapy options are not recommended 1
• Performance status is poor (ECOG ≥2) 1
• Active hepatic decompensation with worsening ascites or encephalopathy is present 4

Do not plan for second-line immunotherapy or TKI therapy after nivolumab failure in Child-Pugh B patients, as no agents are approved for this population. 4 This makes the first-line treatment decision particularly critical.

Real-World Outcomes

Real-world data from German centers showed median overall survival of only 7.5 weeks in unselected Child-Pugh B patients, with Child-Pugh B status significantly associated with poor outcomes. 5 This underscores the importance of careful patient selection and realistic prognostic discussions. 5