替雷利珠单抗联合仑伐替尼一线治疗晚期不可切除肝癌的临床疗效与安全性观察

Clinical Efficacy and Safety Observation of Tislelizumab Combined with Lenvatinib as First-Line Therapy for Advanced Unresectable Hepatocellular Carcinoma

摘要: 目的：本研究旨在探讨替雷利珠单抗联合仑伐替尼对比安慰剂联合仑伐替尼一线治疗晚期不可切除肝癌的临床疗效及安全性。方法：根据入排标准，共纳入42例晚期不可切除的肝癌患者，既往未经过任何治疗，1:1分为观察组和对照组，观察组采用替雷利珠单抗联合仑伐替尼，对照组采用安慰剂联合仑伐替尼。主要终点是无进展生存期(PFS)，次要终点是总生存期(OS)、客观反应率(ORR)和不良事件(AE)。并分析了影响患者生存的预后因素。结果：替雷利珠单抗联合仑伐替尼组中位PFS更长(13.1个月vs 7.1个月，P < 0.05)，明显高于安慰剂联合仑伐替尼组。观察组中位OS较对照组稍有延长，但差异无统计学意义(16.2个月vs 15.0个月，P = 0.2)。未显示Child-Pugh分级、PS评分等是影响OS即PFS的独立预后因素。≥3级治疗相关不良事件(TRAEs)的发生率没有显著差异。观察组11名患者与对照组8名患者(52.4% vs 38.1% P < 0.05)观察到客观反应，有统计学差异；观察组20名患者与对照组18名患者(95.2% vs 85.7% P = 0.325)观察到疾病控制，差异无统计学意义。结论：替雷利珠单抗联合仑伐替尼一线治疗不可切除晚期肝癌患者显示出延长PFS的潜力，提高患者ORR，同时安全性是可耐受的。但仍需更大规模的多中心前瞻性随机对照研究进一步证实上述结论。

Abstract: Objective: This study aimed to investigate the clinical efficacy and safety of tislelizumab combined with lenvatinib versus placebo combined with lenvatinib as first-line treatment for patients with advanced unresectable hepatocellular carcinoma (HCC). Methods: A total of 42 previously untreated patients with advanced unresectable HCC were enrolled in accordance with the inclusion and exclusion criteria, and randomly divided into the observation group and the control group at a ratio of 1:1. The observation group received tislelizumab plus lenvatinib, while the control group was administered placebo plus lenvatinib. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). Additionally, prognostic factors affecting patient survival were analyzed. Results: The median PFS was significantly longer in the tislelizumab-lenvatinib group than in the placebo-lenvatinib group (13.1 months vs. 7.1 months, P < 0.05). The median OS of the observation group was slightly prolonged compared with that of the control group, but the difference was not statistically significant (16.2 months vs. 15.0 months, P = 0.2). Child-Pugh classification, performance status (PS) score, and other factors were not identified as independent prognostic factors for OS or PFS. There was no significant difference in the incidence of grade ≥3 treatment-related adverse events (TRAEs) between the two groups. Objective responses were observed in 11 patients in the observation group and 8 patients in the control group (52.4% vs. 38.1%, P < 0.05), with a statistically significant difference. Disease control was achieved in 20 patients of the observation group and 18 patients of the control group (95.2% vs. 85.7%, P = 0.325), showing no statistically significant difference. Conclusion: Tislelizumab combined with lenvatinib as first-line therapy provide the potential of prolong the median PFS ability and improve the ORR in patients with advanced unresectable HCC, with a tolerable safety profile. However, larger-scale multicenter prospective randomized controlled studies are still needed to further confirm the above conclusions.