Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, Zhejiang, China.
Signal Transduct Target Ther. 2024 Oct 9;9(1):280. doi: 10.1038/s41392-024-01991-1.
Evidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.
经导管动脉化疗栓塞（TACE）治疗不能切除的肝细胞癌（uHCC）的可行性证据仍然有限。本研究旨在探讨 TACE 联合恩沃利单抗和仑伐替尼治疗 uHCC 的疗效和安全性。符合条件的 uHCC 患者在 TACE 后接受恩沃利单抗和仑伐替尼治疗，直至疾病进展、转为手术、无法耐受毒性或死亡。主要终点是根据实体瘤反应评估标准（RECIST）1.1 评估的客观缓解率（ORR）。2022 年 3 月至 2022 年 7 月，38 例患者纳入安全性分析，36 例患者纳入疗效分析。截至数据截止日期（2023 年 12 月 13 日），中位随访时间为 16.9 个月。根据 RECIST 1.1，ORR 为 50%，疾病控制率（DCR）为 83.3%（均为 mRECIST 的 83.3%）。中位无进展生存期（PFS）为 7.58 个月。36 例患者中，17 例转为可切除 HCC，手术转化率为 47.2%，16 例接受手术，R0 切除率为 100%，病理完全缓解（pCR）率为 31.3%。任何级别的治疗相关不良事件（TRAEs）总发生率为 97.4%。52.6%的患者发生 ≥ 3 级 TRAEs。无治疗相关死亡。图像质谱流式细胞术（IMC）分析表明，联合治疗改善了肿瘤微环境的免疫状态，驻留巨噬细胞有可能预测该治疗的疗效。恩沃利单抗加仑伐替尼联合 TACE 具有良好的生存获益和转化率，安全性可耐受。
试验注册 临床试验：NCT05213221。
