Prognostic Benefit of Sequential Locoregional Interventions During First-Line Systemic Therapy for Hepatocellular Carcinoma: Insights from Interaction Analysis of Lenvatinib and Atezolizumab/Bevacizumab.

BACKGROUND: Achieving conversion therapy for advanced hepatocellular carcinoma (HCC) is a promising strategy. However, it remains unclear whether the prognostic impact of these interventions differs depending on the first-line systemic regimen.

PATIENTS AND METHODS: We retrospectively analyzed 189 patients with advanced HCC who received first-line systemic therapy. Independent prognostic factors for overall survival (OS) were identified using Firth's penalized Cox proportional hazards models. Interaction analysis was performed to assess whether the benefit of interventions varied by regimen.

RESULTS: Interventions were significantly associated with improved OS in the entire cohort. Notably, achieving R0 status provided the most substantial survival benefit, with no significant interaction between regimens (P = 0.425; hazard ratio [HR] 0.074 for lenvatinib, HR 0.406 for atezolizumab/bevacizumab). Transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) was also associated with improved OS, showing a more pronounced benefit in the lenvatinib group than in the atezolizumab/bevacizumab group (P = 0.105; HR 0.350 versus 0.726).

CONCLUSIONS: Achieving R0 status through conversion therapy is a universal goal for maximizing OS, regardless of the initial systemic regimen. Lenvatinib may offer a more favorable platform for sequential TACE/HAIC to prolong overall survival compared to atezolizumab/bevacizumab.