Background: Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. Methods: In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n= 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n= 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. Results: The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p< 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%,p= 0.15). Median OS was 22.2 months (95% CI: 8.9–49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6–18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1–3.3,p= 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2–6.3). Conclusion: Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.
背景：关于纳武利尤单抗作为不可切除肝细胞癌（uHCC）二线治疗的有效性和结局数据有限。本研究旨在评估纳武利尤单抗在索拉非尼治疗期间出现疾病进展的uHCC患者中的疗效和安全性。方法：在这项回顾性、观察性、多中心研究中，对索拉非尼治疗耐受但出现疾病进展的成人Child-Turcotte-Pugh A/7B级uHCC患者，转为二线静脉注射纳武利尤单抗治疗（n=42）。同时，选取数量相近、连续且未经筛选的继续接受索拉非尼治疗的患者作为历史对照，无论其肿瘤反应或进展如何（n=38）。主要终点为总生存期（OS，定义为从任一组开始索拉非尼治疗至任何原因死亡的时间），并按意向治疗原则进行分析。结果：整个队列的平均年龄为72.4±10.1岁，其中87.5%为男性，58.8%有潜在病毒病因。除接受纳武利尤单抗治疗的患者合并症更多（70.0% vs. 15.4%）、ECOG-2状态比例更高（21.4% vs. 15.8%）、BCLC C期比例更高（81.0% vs. 47.4%）以及血管外侵犯比例更高（54.4% vs. 21.8%）外（所有比较p<0.05），两个队列的患者特征相似。纳武利尤单抗组中Child-Turcotte-Pugh B级患者比例更高（35.7% vs. 21.1%，p=0.15）。二线纳武利尤单抗治疗的中位OS为22.2个月（95% CI: 8.9–49.8），而仅使用索拉非尼治疗的中位OS为11.0个月（95% CI: 3.6–18.4）（HR 1.93；95% CI: 1.1–3.3，p=0.014）。开始纳武利尤单抗治疗后的中位OS为10.2个月，至疾病进展时间为4.9个月（95% CI: 3.2–6.3）。结论：对于索拉非尼治疗后进展的uHCC患者，纳武利尤单抗是一种有效的二线治疗选择，能显著改善OS。这些早期真实世界数据提供了令人鼓舞的结果，与I/IIa期临床试验结果相似。纳武利尤单抗作为单药治疗值得进一步研究。
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