Which First-Line Treatment Is Most Effective for Advanced Liver Cancer?
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🍃 Advanced HCC: A Paradigm Shift in First-Line Therapy
The network meta-analysis by Celsa et al. (JAMA Oncology, Aug 14, 2025) integrating OS + HR-QoL showed that atezolizumab + bevacizumab provides the most balanced first-line option.
Scope
9 Phase III
Total 6,425 patients
Integrated Outcome
OS + QoL combined
Treatments ranked by both survival and quality of life
Top performer
Atezo + Beva
Best SUCRA across most QoL domains
Alternative
Durva + Treme
Significant OS benefit (HIMALAYA)
What is SUCRA? SUCRA (Surface Under the Cumulative Ranking) is a metric in network meta-analyses that summarizes relative treatment ranking on a 0–100% scale. Higher values indicate higher likelihood of being among the top-ranked options. In QoL, a higher SUCRA means better performance in delaying deterioration.
IMbrave150 · Atezo + Beva vs Sorafenib
Overall survival (OS, months)
Atezo+Beva: 19.2Sorafenib: 13.4
PFS (months)
Atezo+Beva: 6.8Sorafenib: 4.3
Time to QoL deterioration (months)
Atezo+Beva: 11.2Sorafenib: 3.6
HIMALAYA · Durva + Treme vs Sorafenib
Overall survival (OS, months)
Durva+Treme: 16.4Sorafenib: 13.8
- ~25% alive at 4 years
- Delayed QoL deterioration
Tislelizumab
Ranked best for physical function and fatigue (SUCRA 96%). Potential domain-specific benefit.
Alignment with International Guidelines
ASCO 2024: Atezo+Beva, Durva+Treme – strong recommendation
NCCN v1.2025: IO-based combos preferred; TKIs as alternatives
ESMO 2025: Atezo+Beva standard; Durva+Treme valid; TKIs if IO not feasible
Eligibility Criteria
- Child-Pugh A liver function
- ECOG 0–1
- Controlled comorbidities
Special Consideration
Bevacizumab is contraindicated in patients with high-risk esophageal variceal bleeding; alternative regimens required.
Toxicity Profiles (Summary)
TKIs (Sorafenib / Lenvatinib)
- HFSR: high (sora), moderate (lenva)
- Fatigue: common, dose-limiting
- Hypertension: lenva > sora
- Diarrhea: common
Immunotherapy (Atezo / Durva+Treme)
- Fatigue, flu-like symptoms
- Immune-related AEs: hepatitis, thyroiditis, etc.
- Management: hold/dose adjust, steroids
Practical Management
- HFSR: avoid friction, emollients, topical steroids
- HTN: monitor, antihypertensives
- Diarrhea: hydration, loperamide
LEAP-002 (Pembro + Lenva)
- OS: 21.2 vs 19.0 months (did not meet significance)
- Response duration: encouraging
- Lesson: tough to outperform strong control arm
Biomarkers & Personalization
- FGF19 overexpression → predictive for irpagratinib
- Need for prognostic biomarkers in Atezo+Beva
🔑 Conclusion: First-line treatment in advanced HCC should not only extend life but also preserve quality of life. Integrated analyses strongly support atezolizumab + bevacizumab as the most balanced option overall, while durvalumab + tremelimumab offers OS benefit and long-term survivors.
Source: Celsa et al., JAMA Oncology, Aug 14, 2025; IMbrave150 & HIMALAYA phase III data. This content is for educational purposes only, not medical advice.
Sources
Celsa C, Di Maria G, Lombardi P, et al. Integrating Quality of Life and Survival in Systemic Therapy for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis. JAMA Oncol. Published online August 14, 2025. doi:10.1001/jamaoncol.2025.2470
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