Yang Jiajin, Xu Qiuping, Luo Sihao, Wu Jianbing
Department of Oncology, Fengcheng People's Hospital, Fengcheng, 331100, Jiangxi Province, China.
Department of Oncology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang City, 330006, Jiangxi Province, China.
BMC Cancer. 2025 Apr 16;25(1):708. doi: 10.1186/s12885-025-14092-1.
This study evaluated the effectiveness and safety of tislelizumab plus lenvatinib (TL group) and tislelizumab monotherapy (T group) in patients with stage C hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer (BCLC) staging system after lenvatinib failure, and it analyzed the factors influencing the effectiveness of TL as a second-line treatment. This retrospective analysis involved 51 patients treated at a single center between January 2019 and July 2023. Survival outcomes and tumor responses were compared between the TL and T monotherapy groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified using Cox proportional hazard regression models. Among patients with BCLC stage C advanced HCC who experienced lenvatinib treatment failure, median PFS was significantly longer in the TL group than in the T group (6.8 months vs. 4.5 months, p = 0.003), and OS was notably extended in the TL group (14.0 months vs. 10.4 months, p = 0.012). Although the disease control rate (64% vs. 53.8%, p = 0.461) and objective response rate (20% vs. 7.7%, p = 0.202) were numerically higher in the TL group, these differences did not reach significance. Child-Pugh B liver function and tislelizumab monotherapy were independent prognostic factors for poor OS, whereas only tislelizumab monotherapy was an independent prognostic factor for poor PFS, Child-Pugh B was not a prognostic factor for PFS. Subgroup analysis demonstrated the OS benefit of tislelizumab plus lenvatinib in patients with Child-Pugh A liver function (14.0 months vs. 12.0 months, p = 0.013) but not in those with Child-Pugh B liver function (7.7 months vs. 6.1 months, p = 0.225). In the TL group, the most frequent treatment-related adverse events (AEs) were hand-foot skin reaction (32%), hypertension (28%), diarrhea (32%), and hypothyroidism (20%). Grade 3 or higher AEs occurred in 24% of patients in the TL group, and hand-foot skin reaction and diarrhea were the most frequent grade 3 or higher AEs. The incidence of AEs was comparable between the two groups. As a second-line treatment, the combination of tislelizumab and lenvatinib was well tolerated and associated with improved OS and PFS versus tislelizumab alone for patients with advanced HCC, particularly in those with Child-Pugh A liver function.
本研究评估了替雷利珠单抗联合乐伐替尼（TL组）和替雷利珠单抗单药治疗（T组）对巴塞罗那临床肝癌（BCLC）分期系统下C期肝细胞癌（HCC）患者在乐伐替尼治疗失败后的有效性和安全性，并分析了影响TL作为二线治疗有效性的因素。这项回顾性分析纳入了2019年1月至2023年7月在单一中心接受治疗的51例患者。比较了TL组和T单药治疗组的生存结局和肿瘤反应。使用Cox比例风险回归模型确定总生存（OS）和无进展生存（PFS）的预后因素。在经历乐伐替尼治疗失败的BCLC C期晚期HCC患者中，TL组的中位PFS显著长于T组（6.8个月对4.5个月，p = 0.003），且TL组的OS显著延长（14.0个月对10.4个月，p = 0.012）。虽然TL组的疾病控制率（64%对53.8%，p = 0.461）和客观缓解率（20%对7.7%，p = 0.202）在数值上更高，但这些差异未达到统计学意义。Child-Pugh B级肝功能和替雷利珠单抗单药治疗是OS不良的独立预后因素，而只有替雷利珠单抗单药治疗是PFS不良的独立预后因素，Child-Pugh B级不是PFS的预后因素。亚组分析表明，替雷利珠单抗联合乐伐替尼对Child-Pugh A级肝功能患者有OS获益（14.0个月对12.0个月，p = 0.013），但对Child-Pugh B级肝功能患者无此获益（7.7个月对6.1个月，p = 0.225）。在TL组中，最常见的治疗相关不良事件（AE）为手足皮肤反应（32%）、高血压（28%）、腹泻（32%）和甲状腺功能减退（20%）。TL组24%的患者发生3级或更高等级的AE，手足皮肤反应和腹泻是最常见的3级或更高等级的AE。两组之间AE的发生率相当。作为二线治疗，替雷利珠单抗和乐伐替尼联合应用耐受性良好，与单独使用替雷利珠单抗相比，晚期HCC患者的OS和PFS得到改善，尤其是Child-Pugh A级肝功能的患者。
