Reassessing First-Line Treatment in Unresectable HCC: Evidence, Experience, and Individualization

Panelists discuss how patients with unresectable HCC present with dual challenges of managing both the cancer and underlying cirrhotic liver disease, emphasizing the complexity of applying clinical trial data from patients with Child-Pugh A status to the more heterogeneous Child-Pugh B population commonly seen in practice.

Panelists discuss how immunotherapy-based regimens have transformed HCC treatment by achieving median survivals of 16 to 24 months and enabling long-term survival with meaningful percentages of patients living 3 to 5 years, representing a dramatic improvement over the historical 2- to 3-month survival benefit seen with sorafenib.

Panelists discuss how all 3 approved immunotherapy doublets (atezolizumab-bevacizumab, durvalumab-tremelimumab, and nivolumab-ipilimumab) demonstrate superiority over tyrosine kinase inhibitor therapy, with each regimen offering distinct advantages—atezolizumab-bevacizumab for disease control, and dual checkpoint inhibitors for durable complete responses and long-term survival tails.

Panelists discuss how approximately half of patients have soft contraindications to specific regimens, with bevacizumab being avoided in patients with recent bleeding, uncontrolled hypertension, or cardiovascular events, while dual checkpoint inhibitors may be contraindicated in patients with poorly controlled autoimmune diseases.

Panelists discuss how the early survival curve crossing observed in the CheckMate 9DW trial likely reflects lenvatinib’s superior short-term disease control, while emphasizing that the real strength of nivolumab-ipilimumab lies in achieving durable complete responses and unprecedented long-term survival tails.

Panelists discuss how dual checkpoint inhibitors demonstrate significantly higher immune-related adverse event rates (nearly 30% grade 3-4) compared with atezolizumab-bevacizumab, but this increased toxicity is accompanied by meaningfully improved response rates, and the addition of anti-CTLA4 therapy roughly doubles response rates compared with anti-PD1 monotherapy in HCC.

Panelists discuss how immune-related adverse events typically occur between 3 and 15 weeks of treatment, with hepatitis being particularly concerning in patients with cirrhosis and requiring careful differentiation from disease progression or worsening cirrhosis, while high-dose steroids remain first-line treatment with consideration of steroid-sparing agents and potential rechallenge strategies for responding patients.