Introduction Several clinical trials comparing the efficacy and safety of transarterial chemoembolisation (TACE) plus molecular-targeted agents versus TACE alone revealed no clinical benefits in progression-free survival (PFS) or overall survival (OS). Here, we report the final OS analysis from the TACTICS trial, which previously demonstrated significant improvement in PFS with TACE plus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) (NCT01217034). Methods Patients with unresectable HCC were randomised to a TACE plus sorafenib group(N=80) or a TACE alone group(N=76). Patients in the combination treatment group received sorafenib 400 mg once daily for 2–3 weeks before TACE, followed by 800 mg once daily during on-demand conventional TACE sessions until time to untreatable progression. In this trial, TACE-specific PFS was used. TACE-specific PFS is defined as the time from randomization to progressive disease (PD) or death from any cause, and PD was defined as untreatable (UnTACEable) progression, caused by the inability of a patient to further receive or benefit from TACE for reasons that include intrahepatic tumor progression (25% increase vs baseline) according to RECICL, the detection of extrahepatic spread, vascular invasion or transient deterioration of liver function to Child-Pugh C after TACE. Results At the cut-off date of 31 July 2020, 131 OS events were observed. The median OS was 36.2 months with TACE plus sorafenib and 30.8 months with TACE alone (hazard ratio [HR]=0.861; 95% confidence interval [CI), 0.607–1.223; P=0.40, ΔOS, 5.4 months). The updated PFS was 22.8 months with TACE plus sorafenib and 13.5 months with TACE alone (HR=0.661; 95% CI, 0.466–0.938; P=0.02). Post-trial treatments with active procedures/agents were received by 47 (58.8%) patients in the TACE plus sorafenib group and 58 (76.3%) in the TACE alone group (P=0.01). In post hoc analysis, PFS and OS benefit were shown in HCC patients with tumor burden beyond up-to-7 criteria. Conclusions In TACTICS trial, TACE plus sorafenib did not show significant OS benefit over TACE alone; however, clinical meaningful OS prolongation and significantly improved PFS was observed. Thus, the TACE plus sorafenib can be considered a choice of treatment in intermediate stage HCC, especially in patients with high tumor burden. Trial Registration: NCT01217034


中文翻译：

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TACTICS 的最终结果：在不可切除的肝细胞癌患者中比较经动脉化疗栓塞联合索拉非尼与单独经动脉化疗栓塞的随机前瞻性试验


介绍 几项比较经动脉化疗栓塞术 (TACE) 加分子靶向药物与单独 TACE 的疗效和安全性的临床试验显示，在无进展生存期 (PFS) 或总生存期 (OS) 方面没有临床益处。在这里，我们报告了 TACTICS 试验的最终 OS 分析，该试验先前证明 TACE 加索拉非尼治疗不可切除的肝细胞癌 (HCC) 患者的 PFS 显着改善 (NCT01217034)。方法 不可切除的 HCC 患者被随机分为 TACE 加索拉非尼组 (N=80) 或单独 TACE 组 (N=76)。联合治疗组的患者在 TACE 前接受索拉非尼 400 毫克每天一次，持续 2-3 周，随后在按需常规 TACE 疗程期间接受 800 毫克每天一次，直至出现无法治疗的进展。在此试验中，使用了 TACE 特异性 PFS。 TACE 特异性 PFS 定义为从随机分组到疾病进展 (PD) 或任何原因死亡的时间，PD 定义为无法治疗 (UnTACEable) 的进展，是由于患者因某种原因无法进一步接受 TACE 或从 TACE 中受益而引起的其中包括根据 RECICL 的肝内肿瘤进展（与基线相比增加 25%），检测 TACE 后肝外扩散、血管侵犯或肝功能短暂恶化至 Child-Pugh C。结果 截至 2020 年 7 月 31 日截止日，观察到 131 起 OS 事件。 TACE 加索拉非尼的中位 OS 为 36.2 个月，单独 TACE 的中位 OS 为 30.8 个月（风险比 [HR]=0.861；95% 置信区间 [CI]，0.607–1.223； P=0.40，ΔOS，5.4 个月）。 TACE 加索拉非尼更新后的 PFS 为 22.8 个月，单独 TACE 为 13.5 个月（HR=0.661；95% CI，0.466–0.938；P=0.02）。 TACE 加索拉非尼组中有 47 名患者 (58.8%) 接受了积极程序/药物的试验后治疗，单独 TACE 组有 58 名患者 (76.3%) 接受了试验后治疗 (P=0.01)。在事后分析中，肿瘤负荷超过 7 个标准的 HCC 患者显示出 PFS 和 OS 获益。结论 在 TACTICS 试验中，与单独使用 TACE 相比，TACE 加索拉非尼并未显示出显着的 OS 获益；然而，观察到具有临床意义的 OS 延长和 PFS 显着改善。因此，TACE联合索拉非尼可以被认为是中期HCC的治疗选择，特别是对于高肿瘤负荷的患者。 试用注册：NCT01217034