Background The efficacy of anti-programmed cell death (PD)-1 monotherapy in advanced hepatocellular carcinoma (aHCC) is limited, and combination therapy with lenvatinib and pembrolizumab has shown promising results. However, comparative studies between immune monotherapies and combination therapies are lacking. Objectives To investigate the efficacy and safety of anti-PD-1 monotherapy (PD-1) and anti-PD-1 plus lenvatinib (PD-1 + L) in patients with aHCC to guide clinical treatment decisions. Design A retrospective study was conducted on a cohort of patients with aHCC who received either PD-1 monotherapy or PD-1 + L combination therapy between January 2018 and January 2020. Methods The study retrospectively reviewed the medical records of 94 eligible patients with aHCC, with 39 in the PD-1 group and 55 in the PD-1 + L group. The efficacy outcomes, including objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety, were assessed. Results With a median follow-up of 30.1 months, the PD-1 + L group demonstrated a significantly higher ORR (32.7% versus 10.3%, p = 0.013), better DCR (80.0% versus 53.8%, p = 0.012), longer median PFS (10.6 versus 4.4 months, p < 0.001) and longer median OS (18.4 versus 8.5 months, p = 0.013) than PD-1 group. For the responders, the efficacy of the two groups was durable (DOR was 11.6 versus 3.5 months, p = 0.009). Subgroup analyses based on prior tyrosine kinase inhibitor (TKI) treatment and the presence or absence of macrovascular tumor thrombosis or extrahepatic metastases favored the PD-1 + L group. The combination therapy was a good predictor of PFS and OS in multivariate analysis. Grade 3/4 treatment-related adverse events were more common in PD-1 + L group, with higher incidences of hypertension and hand-foot skin reactions. Conclusions PD-1 monotherapy and PD-1 plus lenvatinib combination therapy were well-tolerated in patients with aHCC. PD-1 + L showed significantly better survival benefits than PD-1 monotherapy.

中文翻译：

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抗 PD-1 单一疗法与抗 PD-1 抗体加乐伐替尼治疗晚期肝细胞癌患者的疗效和安全性：真实经验。

背景 抗程序性细胞死亡（PD）-1单药治疗晚期肝细胞癌（aHCC）的疗效有限，乐伐替尼和派姆单抗联合治疗已显示出有希望的结果。然而，缺乏免疫单一疗法和联合疗法之间的比较研究。目的 探讨抗 PD-1 单药治疗 (PD-1) 和抗 PD-1 加乐伐替尼 (PD-1 + L) 对 aHCC 患者的疗效和安全性，以指导临床治疗决策。设计 对 2018 年 1 月至 2020 年 1 月期间接受 PD-1 单药治疗或 PD-1 + L 联合治疗的 aHCC 患者队列进行回顾性研究。方法该研究回顾性审查了 94 名符合条件的 aHCC 患者的医疗记录， PD-1 组有 39 例，PD-1 + L 组有 55 例。评估疗效结果，包括客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）和安全性。结果 中位随访时间为 30.1 个月，PD-1 + L 组表现出显着更高的 ORR（32.7% 对比 10.3%，p = 0.013）、更好的 DCR（80.0% 对比 53.8%，p = 0.012）、更长的疗效与 PD-1 组相比，中位 PFS（10.6 个月与 4.4 个月，p < 0.001）和中位 OS 更长（18.4 个月与 8.5 个月，p = 0.013）。对于应答者来说，两组的疗效是持久的（DOR 分别为 11.6 个月和 3.5 个月，p = 0.009）。基于既往酪氨酸激酶抑制剂 (TKI) 治疗以及是否存在大血管肿瘤血栓形成或肝外转移的亚组分析有利于 PD-1 + L 组。在多变量分析中，联合治疗是 PFS 和 OS 的良好预测因子。PD-1+L组3/4级治疗相关不良事件更常见，高血压和手足皮肤反应发生率更高。结论 PD-1单药治疗和PD-1加乐伐替尼联合治疗在aHCC患者中具有良好的耐受性。PD-1 + L 比 PD-1 单一疗法显示出显着更好的生存益处。