The Role of Lenvatinib in the Evolving HCC Landscape: Optimizing Treatment Strategies From Intermediate to Advanced HCC

Panelists discuss how systemic therapy plays a crucial role in embolization-eligible hepatocellular carcinoma (HCC), particularly for patients with progressive or extensive disease. In locally advanced cases, systemic therapies, including immunotherapy combinations and tyrosine kinase inhibitors (TKIs), are first-line options. Patients typically transition from transarterial chemoembolization (TACE) to systemic therapy upon progression, high tumor burden, or liver function decline.

Panelists discuss how combining systemic therapy with locoregional treatments like transarterial chemoembolization (TACE) aims to enhance therapeutic efficacy by addressing its limitations, such as incomplete tumor necrosis and hypoxia-induced progression. Tyrosine kinase inhibitors (TKIs) like lenvatinib and immune checkpoint inhibitors (ICIs) counteract TACE-induced resistance by inhibiting angiogenesis and boosting immune response, improving overall tumor control.

Panelists discuss how the role of systemic therapy in intermediate-stage hepatocellular carcinoma (HCC) is evolving with combinations like immunotherapy and targeted agents enhancing locoregional treatment. LEAP-012 and EMERALD-1 evaluate lenvatinib + pembrolizumab and durvalumab-based regimens with transarterial chemoembolization (TACE), respectively. Their findings may redefine treatment paradigms, improving outcomes and expanding therapeutic options.

Panelists discuss how emerging evidence suggests that combining transarterial chemoembolization (TACE) with systemic therapy could redefine the standard of care for hepatocellular carcinoma (HCC). Trial outcomes may drive shifts toward more personalized locoregional approaches. However, challenges in implementation include optimizing patient selection, managing toxicity, and ensuring multidisciplinary coordination.

Panelists discuss how current first-line systemic therapies for advanced hepatocellular carcinoma (HCC) include atezolizumab + bevacizumab and durvalumab + tremelimumab, replacing tyrosine kinase inhibitors (TKIs) like sorafenib and lenvatinib. Emerging combinations with anti–PD-L1 agents enhance efficacy. TKI + immune checkpoint inhibitor (ICI) combinations offer synergistic benefits but pose toxicity, cost, and biomarker challenges.

Panelists discuss how ongoing trials in first-line advanced hepatocellular carcinoma (HCC) may reshape treatment paradigms, influencing tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) use. Patient selection depends on clinical (liver function, ECOG status) and biological (PD-L1, VEGF expression) factors. Lenvatinib remains a key TKI, balancing efficacy and safety. As emerging regimens (CARES-310, CheckMate-9DW) gain traction, lenvatinib’s role evolves, with experts assessing its place in monotherapy and combinations.

Panelists discuss how, when a patient progresses to second-line therapy, key considerations include prior treatment response, toxicity, patient comorbidities, and therapeutic goals. Lenvatinib shows potential beyond first-line treatment, offering efficacy in patients progressing on systemic therapies, with emerging data supporting its role in treatment sequencing.

Panelists discuss how lenvatinib has significantly impacted the systemic therapy landscape for hepatocellular carcinoma (HCC) across different stages. As a first-line treatment, it offers a viable alternative to sorafenib, demonstrating noninferior overall survival with improved progression-free survival and response rates. Its role extends to combination regimens and advanced-stage disease management.