Is durvalumab (durvalumab) monotherapy recommended as a first-line treatment for a patient with hepatocellular carcinoma (HCC) classified as Barcelona Clinic Liver Cancer (BCLC) stage C, with a Child-Turcotte-Pugh (CTP) score indicating moderate to severe liver dysfunction and evidence of portal vein tumor thrombus (PVTT)?

Durvalumab Monotherapy for BCLC Stage C HCC with PVTT and Moderate-Severe Liver Dysfunction

Durvalumab monotherapy is NOT recommended as first-line treatment for this patient and should only be considered when both atezolizumab plus bevacizumab and durvalumab plus tremelimumab are contraindicated. 1, 2

Critical Patient Assessment Required

Your patient presents with multiple high-risk features that significantly narrow treatment options:

• BCLC Stage C with portal vein tumor thrombus (PVTT) - confirms advanced disease 1, 2
• Child-Pugh score indicating moderate to severe dysfunction - this is the most critical limiting factor 1, 2

Child-Pugh Status Determines Everything

If Child-Pugh Class A:

• Durvalumab monotherapy is inferior to combination regimens and should NOT be first-line 1, 2
• First-line priority: Durvalumab plus tremelimumab (STRIDE regimen) - median OS 16.43 months, particularly valuable because main portal vein thrombosis was excluded from the HIMALAYA trial, but segmental/lobar PVTT patients were included 1, 2, 3
• Alternative first-line: Atezolizumab plus bevacizumab - median OS 19.2 months, but requires endoscopic variceal screening and management, which may be problematic with PVTT 1, 2
• Durvalumab monotherapy only becomes an option when both combinations are contraindicated (autoimmune disease, bleeding risk, etc.) 1

If Child-Pugh Class B or C:

• No immunotherapy regimens (including durvalumab monotherapy) are recommended - all pivotal trials excluded Child-Pugh B/C patients 1, 2, 4
• Best supportive care is the guideline-recommended approach for Child-Pugh C 1
• Selected Child-Pugh B patients may be considered for locoregional therapies (TACE, HAIC) rather than systemic therapy 5, 6

Why Durvalumab Monotherapy Fails as First-Line

The HIMALAYA trial included a durvalumab monotherapy arm that demonstrated:

• No improvement in progression-free survival compared to sorafenib (HR 0.90,95% CI 0.77-1.05) 1
• Inferior outcomes compared to the durvalumab plus tremelimumab combination 1
• ASCO guidelines explicitly state durvalumab monotherapy is only for patients with contraindications to the preferred combinations 1

PVTT-Specific Considerations

Main portal vein invasion is a contraindication to durvalumab plus tremelimumab (patients were excluded from HIMALAYA), but segmental/lobar PVTT was permitted 1, 2. You must determine the extent of PVTT:

• Subsegmental/segmental PVTT: Both combination regimens remain options if Child-Pugh A 6
• Main portal vein thrombosis: Durvalumab plus tremelimumab is contraindicated; atezolizumab plus bevacizumab becomes preferred if no variceal contraindications 1, 2
• Lobar branch PVTT: Consider locoregional therapies (TARE, HAIC-FO) which show superior outcomes in this population 5, 6

Treatment Algorithm for Your Patient

1. Confirm exact Child-Pugh score (A vs B vs C) - this is non-negotiable 1, 2
2. Determine PVTT extent (subsegmental, segmental, lobar, or main portal vein) 1, 6
3. Assess ECOG performance status (must be 0-1 for any systemic therapy) 1

If Child-Pugh A + ECOG 0-1:

• First choice: Durvalumab plus tremelimumab (if no main PV involvement) 2, 3
• Second choice: Atezolizumab plus bevacizumab (if varices managed and no main PV involvement) 2
• Third choice: Lenvatinib or sorafenib (if both combinations contraindicated) 1
• Durvalumab monotherapy: Only if all above are contraindicated 1

If Child-Pugh B or worse:

• No systemic immunotherapy recommended 2, 4
• Consider locoregional therapy (HAIC-FO shows best outcomes for HCC-PVTT) 5
• Best supportive care if Child-Pugh C 1

Critical Pitfalls to Avoid

• Do not use durvalumab monotherapy when combination regimens are feasible - you sacrifice significant survival benefit 1, 2
• Do not initiate any immunotherapy in Child-Pugh B/C patients - no safety or efficacy data exists 2, 4
• Do not overlook locoregional options for PVTT patients - HAIC-FO may provide superior outcomes compared to systemic therapy alone 5
• Do not assume all PVTT is the same - extent of portal vein involvement dramatically changes treatment eligibility 1, 6