Sun Hui-Chuan, Huang Zhi-Yong, Wen Tianfu, Liu Lianxin, Zhu Xiao-Dong, Zhang Erlei, Li Chuan, Zhang Xiaoyun, Wang Jiabei, Fan Jia, Zhou Jian
Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College of Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China.
J Hepatocell Carcinoma. 2025 May 22;12:1043-1056. doi: 10.2147/JHC.S516478. eCollection 2025.
The risk of hepatocellular carcinoma (HCC) recurrence following surgical resection remains high, approaching 50%-70% at 5 years, with the highest risk occurring in the first year after resection. This study aimed to evaluate the efficacy and safety of lenvatinib as adjuvant therapy for HCC.
In this open-label, single-arm, prospective, multicenter Phase II clinical study, a total of 51 hCC patients with China Liver Cancer (CNLC) stage IIb/IIIa (ie tumor number ≥ 4 or vascular invasion, equivalent to BCLC B/C) who underwent R0 resection 4-6 weeks after curative surgery were enrolled. Patients received lenvatinib for up to 12 months, at a dose of 8 mg/day for body weight < 60 kg, or 12 mg/day for ≥ 60 kg. Patients were followed up every 2 months for a median of 24.1 months.
The median recurrence-free survival (RFS) was 16.1 months, with a 12-month RFS rate of 60.4%, exceeding the historical rate of under 50% in similar high-risk populations. The 12-month overall survival (OS) rate was 93.6%, while median OS was not reached. Treatment-related adverse events (TRAEs) occurred in 88.0% of patients, with ≥ grade 3 TRAEs in 14.0%, including thrombocytopenia and proteinuria in 6.0% of patients each, and leukopenia, neutropenia, elevated aspartate aminotransferase, and elevated alanine aminotransferase in 2.0% of patients each. AEs leading to the interruption of lenvatinib occurred in 6.0% of patients, and dose reduction was required in 18% of patients. No deaths were observed.
Lenvatinib may be an effective adjuvant therapy for patients with CNLC stage IIb/IIIa HCC after R0 hepatectomy. However, the findings are limited by the single-arm design and small patient cohort, necessitating larger randomized controlled trials for validation.
肝细胞癌（HCC）手术切除后复发风险仍然很高，5年复发率接近50%-70%，其中切除后第一年风险最高。本研究旨在评估乐伐替尼作为HCC辅助治疗的疗效和安全性。
在这项开放标签、单臂、前瞻性、多中心II期临床研究中，共纳入51例中国肝癌（CNLC）IIb/IIIa期（即肿瘤数量≥4个或有血管侵犯，相当于巴塞罗那临床肝癌分期系统（BCLC）B/C期）的HCC患者，这些患者在根治性手术后4-6周接受了R0切除。患者接受乐伐替尼治疗长达12个月，体重<60 kg者剂量为8 mg/天，体重≥60 kg者剂量为12 mg/天。患者每2个月随访一次，中位随访时间为24.1个月。
中位无复发生存期（RFS）为16.1个月，12个月RFS率为60.4%，超过了类似高危人群中历史上低于50%的发生率。12个月总生存率（OS）为93.6%，中位OS未达到。88.0%的患者发生了治疗相关不良事件（TRAEs），≥3级TRAEs的发生率为14.0%，其中血小板减少症和蛋白尿各占6.0%，白细胞减少症、中性粒细胞减少症、天冬氨酸转氨酶升高和丙氨酸转氨酶升高各占2.0%。导致乐伐替尼中断的不良事件发生在6.0%的患者中，18%的患者需要减量。未观察到死亡病例。
乐伐替尼可能是CNLC IIb/IIIa期HCC患者R0肝切除术后有效的辅助治疗方法。然而，这些结果受单臂设计和小样本队列的限制，需要更大规模的随机对照试验进行验证。
