Multicenter single-arm phase II trial of lenvatinib in patients with advanced hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab

作者：Hyung‐Don Kim, Sun Jin Sym, Hong Jae Chon, Moonho Kim, Jung Hun Kang, Baek‐Yeol Ryoo, Choong‐kun Lee, Joo-Hyun Hong, Hyewon Ryu, Woo Kyun Bae, Hyeyeong Kim, Hyunho Kim, Jin Won Kim, Tae‐Yong Kim, Changhoon Yoo · 发表于：Journal of Hepatology · 年份：2025 · DOI：10.1016/j.jhep.2025.08.020 · 被引用次数：22 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Liver physiology and pathology、Hepatitis B Virus Studies

BACKGROUND & AIMS: Atezolizumab plus bevacizumab (atezo-bev) is the global standard first-line therapy for unresectable hepatocellular carcinoma (uHCC). However, most patients eventually experience disease progression and optimal second-line strategies after atezo-bev failure remain unclear. Prospective evidence supporting multikinase inhibitors in this context is limited. METHODS: This investigator-initiated, multicenter, single-arm study (KCSG HB23-04) enrolled 50 patients with uHCC who progressed after first-line atezo-bev across 13 sites between August 2023 and May 2024. Patients received second-line lenvatinib at 12 mg or 8 mg daily, depending on body weight, until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival. Secondary endpoints were overall survival, objective response rate, disease control rate, duration of response, and safety. RESULTS: Of the 50 patients enrolled, the median age was 66 years, and 72% had a viral etiology. The median time to progression with atezo-bev was 6.5 months. During a median follow-up of 12.6 months, the median progression-free survival was 5.4 months (95% CI 4.2-7.1) (>4.5 months), meeting the prespecified primary endpoint. Median overall survival was 9.8 months (95% CI 8.1-NR). The objective response rate was 14.0%, and the disease control rate was 82.0%. The median duration of response was 9.4 months. Survival outcomes were different according to the objective response with lenvatinib, bu...