一项针对大尺寸（≥7厘米）不可切除肝细胞癌患者的前瞻性单臂2期研究，该研究采用低剂量化疗与空白微球联合低剂量乐伐替尼及微波消融进行改良经动脉化疗栓塞：TALEM试验
A Prospective, Single-Arm, Phase 2 Study of Modified Transarterial Chemoembolization Using Low-Dose Chemotherapy with Blank Microspheres Plus Low-Dose Lenvatinib and Microwave Ablation in Patients with Large (≥7 cm) Unresectable Hepatocellular Carcinoma: The TALEM Trial.
作者信息
Huang Zhi-Mei, Han Xue, Wang Jian, Gu Ling, Tang Lu, Wu Shao-Yong, Di Tian, Hou Ying-Wen, Lau Wan Yee, Jiang Yi-Quan, Huang Jin-Hua
机构信息
Department of Minimally Invasive Interventional Therapy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
出版信息
Liver Cancer. 2024 Jan 29;13(4):438-450. doi: 10.1159/000536518. eCollection 2024 Aug.
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 < 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.
引言
对于无法切除的大型肝细胞癌（HCC）患者，传统经动脉化疗栓塞术（cTACE）的疗效仍不尽人意。本研究探讨了使用空白微球低剂量化疗（BMS-TACE）联合低剂量乐伐替尼（LD-LEN）及微波消融（MWA）对无法切除的大型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，符合七项以上标准、最大肿瘤直径≥7 cm、无大血管侵犯或肝外转移的无法切除的HCC患者，接受初始BMS-TACE（碘油、低剂量阿霉素和洛铂各30 mg，以及空白微球；大多数患者随后进行改良和重复治疗）联合LD-LEN（4-8 mg/天）及MWA。主要终点为降期率（DSR）；次要终点为客观缓解率（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，共纳入43例患者。中位随访时间为21.2个月。最大肿瘤直径中位数为11.2 cm（四分位间距[IQR]，7-25）。在接受BMS-TACE和LD-LEN后，37例（86.0%）患者出现降期，其中32例接受了MWA，8例未接受MWA即达到完全缓解（CR）。ORR为93.0%（32例[74.4%]CR，8例[18.6%]部分缓解）。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-髓源性抑制细胞显著下降，CXCR5+/CD8+和CXCR5+/CD4+T细胞早期升高（均P<0.05）。
结论
对于符合七项以上标准、最大肿瘤直径≥7 cm、无大血管侵犯或肝外转移的无法切除的大型HCC患者，BMS-TACE联合LD-LEN及MWA显示出有前景的疗效和可耐受的毒性。
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