Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No.123, Dapi Rd., Niaosong Dist, Kaohsiung City, 833, Taiwan.
School of Medicine, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
BMC Cancer. 2022 Nov 8;22(1):1153. doi: 10.1186/s12885-022-10271-6.
The approved dose of nivolumab is 3 mg/kg or a flat dose of 240 mg for indications. There is no dose-response relationship for nivolumab; therefore, a low-dose regimen may be an option to reduce financial toxicity. This study was designed to investigate the efficacy and safety of low-dose nivolumab in the management of hepatocellular carcinoma (HCC).
We retrospectively reviewed patients with HCC who received 20 or 100 mg of nivolumab intravenously every 2 weeks. The objective response rate was determined in accordance with the Response Evaluation Criteria in Solid Tumors criteria version 1.1. The Cox regression model and Kaplan-Meier method were used to analyze hazard factors, progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
In total, 78 patients were enrolled, including 49 with hepatitis B virus (HBV) and 23 with hepatitis C virus (HCV). All patients were staged as Barcelona Clinic Liver Cancer stage C, and 20 patients were classified as having Child-Pugh classification B (7). Nivolumab 20 mg was an independent prognostic factor for better PFS, and albumin-bilirubin grade 1 was the independent prognostic factor for superior OS in the multivariate analyses. Patients with better HBV (HBV DNA < 500 IU/ml) and HCV (HCV RNA undetectable) controls had superior OS. All AEs were grade 1-2 in severity, and all patients tolerated nivolumab without treatment interruption or dose adjustment. Additionally, 31 patients underwent subsequent therapy after nivolumab treatment.
Low-dose nivolumab may be effective with manageable toxicity and can be an alternative option to reduce financial toxicity in patients with advanced HCC who cannot afford the high cost of immune checkpoint inhibitors in real-world practice.
纳武利尤单抗的批准剂量为 3mg/kg 或固定剂量 240mg，适用于各种适应证。纳武利尤单抗无剂量反应关系，因此低剂量方案可能是降低经济毒性的一种选择。本研究旨在探讨低剂量纳武利尤单抗治疗肝细胞癌（HCC）的疗效和安全性。
我们回顾性分析了接受每 2 周静脉注射 20 或 100mg 纳武利尤单抗的 HCC 患者。根据实体瘤反应评价标准 1.1 版确定客观缓解率。采用 Cox 回归模型和 Kaplan-Meier 法分析危险比、无进展生存期（PFS）和总生存期（OS）。采用美国国立癌症研究所不良事件通用术语标准 5.0 评估不良事件（AE）。
共纳入 78 例患者，其中乙型肝炎病毒（HBV）感染者 49 例，丙型肝炎病毒（HCV）感染者 23 例。所有患者均为巴塞罗那临床肝癌分期 C 期，20 例患者为 Child-Pugh 分级 B（7）。多因素分析显示，纳武利尤单抗 20mg 是 PFS 更好的独立预后因素，白蛋白-胆红素 1 级是 OS 更优的独立预后因素。HBV（HBV DNA<500IU/ml）和 HCV（HCV RNA 不可检测）控制较好的患者 OS 更佳。所有 AE 均为 1-2 级，所有患者均能耐受纳武利尤单抗，无需中断治疗或调整剂量。此外，31 例患者在纳武利尤单抗治疗后接受了后续治疗。
低剂量纳武利尤单抗可能具有疗效，且毒性可管理，对于无法负担免疫检查点抑制剂高昂费用的晚期 HCC 患者，可能是一种降低经济毒性的替代选择。
