Lenvatinib continuation versus regorafenib in treating hepatocellular carcinoma after lenvatinib failure

Hepatocellular carcinoma (HCC) represents a major global health burden. Despite lenvatinib's established role as first-line therapy for advanced HCC, the optimal sequential strategy after its failure remains uncertain. This study compared the efficacy and safety of lenvatinib continuation versus switching to regorafenib following first-line lenvatinib progression.

A retrospective analysis was conducted on 107 consecutive HCC patients treated with lenvatinib. Patients were divided into two groups based on their second-line treatment: the regorafenib group (LEN-RG, 49 patients) and the lenvatinib continuation group (LEN-CON, 58 patients). Baseline characteristics were collected, and overall survival (OS), post-progression survival (PPS), total progression-free survival (TPFS), and post-second-line progression-free survival (PFS) were assessed.

The median OS for the LEN-CON group was 34.4 months [95% confidence interval (CI): 22.4-46.4], compared to 21.8 months (95% CI: 18.56-25.05) in the LEN-RG group [hazard ratio (HR) 0.64, 95% CI: 0.40-1.02, P=0.058]. The median PPS was 25.87 months (95% CI: 15.35-36.38) in the LEN-CON group, compared to 15.33 months (95% CI: 7.39-23.28) in the LEN-RG group (HR 0.58, 95% CI: 0.37-0.93, P=0.019). No significant differences were observed between the groups in TPFS or Post-Second-Line PFS. Multivariate analysis identified Eastern Cooperative Oncology Group (ECOG), extrahepatic metastasis, combined programmed cell death 1 (PD-1) therapy, nodule number, and treatment strategy as independent prognostic factors for PPS. Subgroup analysis indicated clinical benefits in PPS for LEN-CON patients with ECOG 0, Child-Pugh A, male gender, combined PD-1 therapy, multiple tumors, and alpha-fetoprotein (AFP) ≤400 ng/mL. Common adverse events (AEs) were similar between the two groups, with elevated ALT more frequent in the LEN-RG group.

Continuing lenvatinib as second-line therapy after failure may offer sustained survival benefits and demonstrate favorable efficacy and safety in real-world clinical practice.