The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Third Affiliated Hospital, Naval Medical University, Shanghai, China.
Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Immunol. 2023 Jul 7;14:1198562. doi: 10.3389/fimmu.2023.1198562. eCollection 2023.
Reports on Lenvatinib-based therapies show promising treatment outcomes for patients with unresectable hepatocellular carcinoma (uHCC). However, the effect and safety of Lenvatinib-based therapies still need to be further studies.
This was a retrospective, single-center study on the safety and treatment efficacy of Lenvatinib-based combination therapies for uHCC Patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR).
Of 91 patients, there were 16 females and 75 males with uHCC who received systemic therapies based on Lenvatinib in our center. Forty-six patients (50.5%) received Lenvatinib combined with PD-1 antibody treatment. All these patients also received local therapy with the exception of 2 patients. The remaining 36 patinets received Lenvatinib combined with transcatheter arterial chemoembolization (TACE), 1 patient treated Lenvatinib combined with radiotherapy, 8 patients received Lenvatinib alone. At a median treatment time of 8 months, the objective response rate (ORR) of the entire cohort was 58.2% (53 patients), including 7 patients with CR and 46 patients with PR. 21 patients (23.1%) had SD. The disease control rate (DCR) of all patients was 81.3% (74 patients). However, 17 patients (18.7%) developed PD. The 1- and 2-year cumulative OS rates for the entire cohort were 66.8% and 39.3%, while the corresponding PFS rates were 38.0% and 17.1%, respectively. Univariate and multivariate Cox regression analysis revealed multiple tumor sites to be an independent OS risk factor for uHCC patients (HR=2.204, 95% CI=1.104-4.399, =0.025). The most frequently reported adverse events in all patients were AST elevation (51.6%), followed by hypertension (33.0%), ALT elevation (26.4%), and decreased appetite (25.3%). After a combination treatment of Lenvatinib-based therapies, 15 patients met the criteria for salvage liver resection and underwent down-staging hepatectomy with a curative intent. The combination of PD-1 treatment was not very effective in improving the prognosis of uHCC patients treated with Lenvatinib combined with TACE.
Our study demonstrated that a proportive of patients benefited from Lenvatinib-based combination therapies with manageable safety profiles, allowing these patients to undergo downstaging surgery with curative intent.
仑伐替尼为基础的治疗方案报告显示，不可切除肝细胞癌（uHCC）患者的治疗结果有很大的改善。然而，仑伐替尼为基础的治疗方案的疗效和安全性仍需进一步研究。
这是一项回顾性、单中心研究，评估仑伐替尼为基础的联合治疗方案治疗不可切除肝细胞癌患者的安全性和疗效。主要终点是无进展生存期（PFS）和总生存期（OS）。次要终点是疾病进展（PD）、疾病稳定（SD）、部分缓解（PR）和完全缓解（CR）。
在我们中心，91 例 uHCC 患者接受了基于仑伐替尼的系统治疗，其中 16 例为女性，75 例为男性。46 例（50.5%）患者接受了仑伐替尼联合 PD-1 抗体治疗。所有这些患者均接受了局部治疗，除了 2 例患者。其余 36 例患者接受了仑伐替尼联合经导管动脉化疗栓塞术（TACE）治疗，1 例患者接受了仑伐替尼联合放疗治疗，8 例患者单独接受了仑伐替尼治疗。在中位治疗时间为 8 个月时，全队列的客观缓解率（ORR）为 58.2%（53 例），包括 7 例 CR 和 46 例 PR。21 例（23.1%）患者为 SD。所有患者的疾病控制率（DCR）为 81.3%（74 例）。然而，17 例（18.7%）患者发生 PD。全队列的 1 年和 2 年累积 OS 率分别为 66.8%和 39.3%，相应的 PFS 率分别为 38.0%和 17.1%。单因素和多因素 Cox 回归分析显示，多个肿瘤部位是 uHCC 患者 OS 的独立危险因素（HR=2.204，95%CI=1.104-4.399，=0.025）。所有患者中最常报告的不良事件是 AST 升高（51.6%），其次是高血压（33.0%）、ALT 升高（26.4%）和食欲下降（25.3%）。在仑伐替尼为基础的联合治疗后，15 例患者符合挽救性肝切除术的标准，并进行了降期肝切除术，以达到治愈的目的。PD-1 联合治疗对提高仑伐替尼联合 TACE 治疗的 uHCC 患者的预后效果并不明显。
我们的研究表明，一部分患者从仑伐替尼为基础的联合治疗方案中受益，且安全性可控，使这些患者能够进行降期手术，以达到治愈的目的。
Zotero 插件
