Introduction For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (cTACE) remains suboptimal. This study investigated the efficacy and safety of modified TACE using low-dose chemotherapy with blank microspheres (BMS-TACE) plus low-dose lenvatinib (LD-LEN) and microwave ablation (MWA) in patients with large unresectable HCC. Methods In this prospective, single-arm, phase 2 study, patients with unresectable HCC exceeding the up-to-seven criteria, with maximum tumor diameter ≥7 cm, and without macrovascular invasion or extrahepatic metastases, received initial BMS-TACE (lipiodol, low-dose doxorubicin, and lobaplatin up to 30 mg each, and blank microspheres; subsequently modified and repeated in most patients) plus LD-LEN (4-8 mg/day) and MWA. The primary endpoint was downstaging rate (DSR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Results From November 2019 to March 2022, 43 patients were enrolled. Median follow-up was 21.2 months. Median largest tumor diameter was 11.2 cm (interquartile range [IQR], 7-25). Following BMS-TACE and LD-LEN, downstaging occurred in 37 (86.0%) patients, 32 of whom received MWA, and 8 of whom had a complete response (CR) without MWA. ORR was 93.0% (CR in 32 [74.4%] and partial response in 8 [18.6%] patients). The 1-, 2-, and 3-year PFS rates were 57.5%, 25.9%, and 18.1%, respectively (median PFS, 14.7 months [95% CI: 8.1-19.5]). The 1-, 2-, and 3-year OS rates were 85.8%, 67.7%, and 61.6%, respectively (median OS, 36.4 months [95% CI: 26.8-not reached]). After BMS-TACE, a significant decline in CD11b+/CD33+/HLA-DR- myeloid-derived suppressor cells and early elevation in CXCR5+/CD8+ and CXCR5+/CD4+ T cells were observed (both p < 0.05). Conclusion BMS-TACE plus LD-LEN and MWA resulted in promising efficacy and tolerable toxicity in patients with large unresectable HCC exceeding the up-to-seven criteria with a maximum tumor diameter ≥7 cm and without macrovascular invasion or extrahepatic metastases.

中文翻译：

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一项前瞻性、单臂、2 期研究，针对大型（≥7 cm）不可切除的肝细胞癌患者，使用空白微球低剂量化疗加低剂量乐伐替尼和微波消融进行改良经动脉化疗栓塞：TALEM 试验。


简介 对于无法切除的大肝细胞癌 (HCC) 患者，传统经动脉化疗栓塞 (cTACE) 的效果仍然不够理想。本研究调查了使用空白微球低剂量化疗 (BMS-TACE) 加低剂量乐伐替尼 (LD-LEN) 和微波消融 (MWA) 对大型不可切除 HCC 患者进行改良 TACE 的疗效和安全性。方法 在这项前瞻性、单臂、2 期研究中，超过七项标准的不可切除 HCC 患者，最大肿瘤直径≥7 cm，无大血管侵犯或肝外转移，接受初始 BMS-TACE（碘化油、低剂量阿霉素和洛铂各 30 毫克，以及空白微球；随后在大多数患者中进行修改和重复）加上 LD-LEN（4-8 毫克/天）和 MWA。主要终点是降期率（DSR）；次要终点是客观缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和不良事件。结果 2019年11月至2022年3月，共入组43例患者。中位随访时间为 21.2 个月。中位最大肿瘤直径为 11.2 cm（四分位距 [IQR]，7-25）。 BMS-TACE 和 LD-LEN 后，37 名患者 (86.0%) 发生降期，其中 32 名患者接受了 MWA，其中 8 名患者在未接受 MWA 的情况下获得了完全缓解 (CR)。 ORR 为 93.0%（32 名患者完全缓解 [74.4%]，8 名患者部分缓解 [18.6%]）。 1 年、2 年和 3 年 PFS 率分别为 57.5%、25.9% 和 18.1%（中位 PFS，14.7 个月 [95% CI：8.1-19.5]）。 1 年、2 年和 3 年 OS 率分别为 85.8%、67.7% 和 61.6%（中位 OS，36.4 个月 [95% CI：26.8 - 未达到]）。 BMS-TACE 后，观察到 CD11b+/CD33+/HLA-DR- 骨髓源性抑制细胞显着下降，CXCR5+/CD8+ 和 CXCR5+/CD4+ T 细胞早期升高（均 p < 0.05）。结论 BMS-TACE联合LD-LEN和MWA对超过7个标准、最大肿瘤直径≥7 cm且无大血管侵犯或肝外转移的不可切除的大肝癌患者具有良好的疗效和可耐受的毒性。