Introduction Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC), but recurrence after TACE is common. The present phase 2, prospective, multicenter, single-arm trial, the TACTICS-L trial, investigated the efficacy and safety of TACE plus lenvatinib (LEN), a drug that more strongly promotes vascular normalization and has a better objective response rate (ORR) than sorafenib (jRCTs031180074). Methods Participants were patients with HCC who had not previously received systemic therapy, hepatic arterial infusion chemotherapy, or immunotherapy and who were ineligible for resection or percutaneous ablation therapy. LEN was to be administered 14-21 days before the first TACE, stopped 2 days before TACE, and resumed 3 days after TACE. Key inclusion criteria were unresectable HCC, Child-Pugh A liver function, 0-2 prior TACE sessions, tumor size ≤10 cm, number of tumors ≤10, and ECOG performance status 0-1. Key exclusion criteria were vascular invasion and extrahepatic spread. The primary endpoint was progression-free survival (PFS) by RECICL, and secondary endpoints were time to untreatable progression, ORR, overall survival (OS), and safety. Results A total of 62 HCC patients were enrolled in this trial. The median age was 72 years, 77.4% of patients were men, and 95.2% had PS 0. The primary endpoint of median PFS was 28.0 months (90% confidence interval [CI] 25.1-31.0) after a minimum 24 months of follow-up. The secondary endpoint of median OS was not reached (90% CI 35.5 months-NR). LEN-TACE achieved a high response rate and high complete response (CR) rate (4 weeks after the first TACE: ORR 79.0%, CR rate 53.2%; best response: ORR 88.7%, CR rate 67.7%) by RECICL. Exploratory subgroup analyses showed that the characteristics of responders/nonresponders (ORR and CR rate) were similar and that LEN-TACE would be effective in all subgroups, including the population in whom TACE alone would be less likely to be curative (e.g., patients with the non-simple nodular type or a high tumor burden). The relative dose intensity of LEN before the first TACE was important for achieving higher CR rate/ORR by LEN-TACE. No new safety concerns were observed. Conclusion The results of this trial provide encouraging evidence, supporting the efficacy and favorable safety profile of LEN-TACE in patients who are ineligible for locoregional therapy.

中文翻译：

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经动脉化疗栓塞治疗与乐伐替尼联合治疗不可切除的中期肝细胞癌患者的 2 期前瞻性、多中心、单臂试验：TACTICS-L 试验。


简介 经动脉化疗栓塞 (TACE) 是不可切除的中期肝细胞癌 (HCC) 的标准治疗方法，但 TACE 后复发很常见。目前的 2 期前瞻性、多中心、单臂试验 TACTICS-L 试验研究了 TACE 联合仑伐替尼 (LEN) 的疗效和安全性，LEN 是一种更强有力地促进血管正常化并具有更好的客观缓解率 (ORR) 的药物。 ）优于索拉非尼（jRCTs031180074）。方法 受试者为既往未接受过全身治疗、肝动脉灌注化疗或免疫治疗且不适合切除或经皮消融治疗的 HCC 患者。 LEN 将在第一次 TACE 前 14-21 天施用，在 TACE 前 2 天停止，并在 TACE 后 3 天恢复。主要纳入标准为不可切除的 HCC、Child-Pugh A 肝功能、0-2 次既往 TACE 疗程、肿瘤大小≤10 cm、肿瘤数量≤10 以及 ECOG 表现状态 0-1。主要排除标准是血管侵犯和肝外扩散。主要终点是 RECICL 的无进展生存期 (PFS)，次要终点是达到无法治疗进展的时间、ORR、总生存期 (OS) 和安全性。结果 共有 62 名 HCC 患者入组本试验。中位年龄为 72 岁，77.4% 的患者为男性，95.2% 的 PS 为 0。在至少 24 个月的随访后，中位 PFS 的主要终点为 28.0 个月（90% 置信区间 [CI] 25.1-31.0）。向上。未达到中位 OS 的次要终点（90% CI 35.5 个月-NR）。根据RECICL，LEN-TACE取得了高缓解率和高完全缓解（CR）率（首次TACE后4周：ORR 79.0％，CR率53.2％；最佳缓解：ORR 88.7％，CR率67.7％）。 探索性亚组分析表明，应答者/无应答者的特征（ORR 和 CR 率）相似，LEN-TACE 在所有亚组中均有效，包括单独 TACE 不太可能治愈的人群（例如患有以下疾病的患者）：非单纯结节型或高肿瘤负荷）。第一次 TACE 之前 LEN 的相对剂量强度对于通过 LEN-TACE 实现更高的 CR 率/ORR 很重要。没有观察到新的安全问题。结论 该试验的结果提供了令人鼓舞的证据，支持 LEN-TACE 对于不适合局部治疗的患者的疗效和良好的安全性。