Which First-Line Treatment Is Most Effective for Advanced Liver Cancer?
🍃 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.
- ~25% alive at 4 years
- Delayed QoL deterioration
Ranked best for physical function and fatigue (SUCRA 96%). Potential domain-specific benefit.
- Child-Pugh A liver function
- ECOG 0–1
- Controlled comorbidities
Bevacizumab is contraindicated in patients with high-risk esophageal variceal bleeding; alternative regimens required.
- HFSR: high (sora), moderate (lenva)
- Fatigue: common, dose-limiting
- Hypertension: lenva > sora
- Diarrhea: common
- Fatigue, flu-like symptoms
- Immune-related AEs: hepatitis, thyroiditis, etc.
- Management: hold/dose adjust, steroids
- HFSR: avoid friction, emollients, topical steroids
- HTN: monitor, antihypertensives
- Diarrhea: hydration, loperamide
- OS: 21.2 vs 19.0 months (did not meet significance)
- Response duration: encouraging
- Lesson: tough to outperform strong control arm
- 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.
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
