Cancer Therapy AdvisorTreatment Approaches for Advanced Hepatocellular Carcinoma From ASCO GI 2024

Evolving Paradigms in Advanced Hepatocellular Carcinoma: Navigating Through New Therapeutic Horizons

At the 2024 ASCO GI Symposium, experts gathered to discuss groundbreaking developments in the treatment of advanced hepatocellular carcinoma (HCC). Richard S. Finn, MD, from UCLA, provided critical insights into the latest therapeutic strategies and their implications for patient care. These insights reflect a dynamic shift in the management of HCC, emphasizing novel combinations and sequences of therapies that promise enhanced outcomes for patients.

Key Points:

• Lenvatinib combined with hepatic arterial infusion chemotherapy using cisplatin (lenv+CDDP) shows potential efficacy as a second-line therapy post-immunotherapy in advanced HCC.
• The triple combination of lenvatinib, pembrolizumab, and quavonlimab achieved a 37.4% objective response rate in advanced HCC, suggesting notable activity.
• Cabozantinib continues to be a valuable treatment option in second, third, or subsequent lines of therapy, with real-world evidence supporting its efficacy post-frontline immunotherapy.
• Extended treatment with atezolizumab plus bevacizumab (atez+bevi) increases risks of adverse events like thyroid dysfunction, skin toxicity, hypertension, and proteinuria.
• A Japanese study indicates that atez+bevi’s efficacy as second-line treatment in advanced HCC is comparable to its frontline use, without evident resistance post-lenvatinib.
• Severe adverse events with atez+bevi include immune-related issues and on-target effects of bevacizumab, like hypertension and proteinuria.
• Lenv+CDDP versus single-agent lenvatinib shows improved median PFS and OS for patients who previously underwent immunotherapy.
• For long-term atez+bevi therapy, patient monitoring for bevacizumab-related adverse events like hypertension and proteinuria is crucial.
• The KEYSTEP-004 study’s findings on the lenvatinib, quavonlimab, and pembrolizumab triplet highlight a potential new direction in first-line advanced HCC treatments.
• Cabozantinib’s role remains vital in the post-immunotherapy landscape of HCC, with its efficacy supported by the CELESTIAL study and real-world evidence.

“As we await new data on cabozantinib in liver cancer, we anticipate increasing RWE of its activity in the second and third line after prior IO.”
– Richard S. Finn, MD

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