Efficacy and safety of transcatheter arterial chemoembolization in combination with lenvatinib in treatment of intermediate and advanced primary liver cancer：a meta<b>-</b>analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Baojiang ,  CONG Peng

Division of Hepatobiliary Surgery, Nanchong Central Hospital, Second Clinical Medical College of North Sichuan Medical, Nanchong, Sichuan 637000, P. R. China;

Corresponding author：

CONG Peng, Email: 157095916@qq.com

Keywords：

primary liver cancer; transcatheter arterial chemoembolization; lenvatinib; meta-analysis

DOI：

10.7507/1007-9424.202308015

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To evaluate systematically the effectiveness and safety of transcatheter arterial chemoembolization (TACE) in combination with lenvatinib (LEN) in the treatment of intermediate and advanced primary liver cancer (PLC). Methods The relevant literature was comprehensively searched in the CNKI, VIP, Ovid, Schopus, PubMed, and other databases from the establishment of the databases to March 14, 2023. The literature was obtained according to the search strategy and the inclusion and exclusion criteria, and the data were extracted and the literature quality was evaluated. The Revman 5.4 software and Stata 15.1 software were used to conduct the meta-analysis to evaluate the effect of TACE+LEN regimen on the objective response rate (ORR), disease control rate (DCR), overall survival (OS), as well as secondary outcome indicators such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha fetoprotein (AFP), and hypertension, diarrhea, hand-foot disease, fatigue, proteinuria, and fever for the patients with PLC. Results A total of 15 relevant literature was included, including 1 219 patients with PLC, 591 of whom treated with TACE+LEN and 628 treated with TACE alone. The meta-analysis results showed that the TACE+LEN regimen could increase ORR and DCR and prolong OS (P<0.01), as well as effectively decrease AFP level (P<0.01). However, TACE+LEN regimen increased the risks of hypertension, diarrhea, hand-foot disease, fatigue, and proteinuria as compared with TACE alone treatment (P<0.05). However, there were no statistical impacts on AST and ALT, or the risk of fever (P>0.05). Conclusion From the results of this meta-analysis, TACE+LEN regimen has a certain efficacy in treatment of intermediate and advanced PLC, but prevention of its related complications is paid attention to.

Citation： WANG Baojiang, CONG Peng. Efficacy and safety of transcatheter arterial chemoembolization in combination with lenvatinib in treatment of intermediate and advanced primary liver cancer：a meta-analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(12): 1444-1451. doi: 10.7507/1007-9424.202308015 Copy

1.	Ferlay JEM, Lam F, Colombet M, et al. Global cancer observatory: cancer today. Lyon: International Agency for Research on Cancer, 2020.https://gco.iarc.fr/today (accessed Feb 27, 2021).
2.	Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6.
3.	Garg T, Shrigiriwar A, Habibollahi P, et al. Intraarterial therapies for the management of hepatocellular carcinoma. Cancers (Basel), 2022, 14(14): 3351.
4.	Zou X, Xu Q, You R, et al. Efficacy and safety of TACE combined with regorafenib plus PD-1 inhibitor in the treatment of hepatocellular carcinoma after sorafenib resistance. J Hepatocell Carcinoma, 2023, 10: 267-279.
5.	Watanabe T, Koyama N. Preclinical study for antitumor mechanism of lenvatinib and clinical studies for hepatocellular carcinoma. Nihon Yakurigaku Zasshi, 2019, 153(5): 242-248.
6.	Mei Z, Gao X, Pan C, et al. Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1⁺ CD8⁺ T cells in HCC via blocking VEGFR2. Cancer Sci, 2023, 114(4): 1284-1296.
7.	朱孟超, 张庆桥, 徐浩, 等. CalliSpheres载药微球治疗原发性肝癌并发肝脓肿4例分析. 介入放射学杂志, 2020, 29(9): 939-941.
8.	中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版). 中国实用外科杂志, 2022, 42(3): 241-273.
9.	张凤琦, 翁凌凌. 仑伐替尼联合肝动脉化疗栓塞术对中晚期肝癌患者的影响. 中外医学研究, 2022, 20(31): 33-37.
10.	张萌, 沙金平, 高毅, 等. 仑伐替尼联合肝癌介入化疗栓塞术在中晚期肝癌患者中的应用. 中西医结合肝病杂志, 2022, 32(3): 275-276.
11.	钟明艳, 冷幸新, 刘波, 等. 乐伐替尼联合TACE治疗不可手术切除原发性肝癌的临床研究. 江西医药, 2022, 57(1): 20-23.
12.	冯锦荣, 何沙, 陈鹏贻, 等. 经导管肝动脉化疗栓塞联合仑伐替尼治疗对晚期肝癌患者肿瘤坏死体积及并发症的影响. 中文科技期刊数据库(引文版)医药卫生, 2022(12): 43-46.
13.	李冰, 马南, 杨胜楠, 等. 仑伐替尼联合经导管动脉栓塞化疗治疗老年原发性肝癌的疗效. 癌症进展, 2022, 20(11): 1121-1124.
14.	刘耀鸿, 林宜圣, 杨荣焕, 等. 仑伐替尼联合肝动脉化疗栓塞术对中晚期原发性肝癌患者近期疗效、T淋巴细胞免疫功能及预后的影响. 临床误诊误治, 2022, 35(7): 60-63.
15.	艾宁, 杨凯, 王永中, 等. 经肝动脉灌注化疗栓塞术联合甲磺酸仑伐替尼在中晚期肝癌患者中的应用. 中华实验外科杂志, 2022, 39(5): 938-940.
16.	王洪云. 甲磺酸仑伐替尼联合TACE治疗中晚期原发性肝癌的临床效果及安全性分析. 中国医学创新, 2020, 17(31): 6-9.
17.	刘娟, 廖豪杰, 袁国盛, 等. 肝动脉化疗栓塞术联合仑伐替尼治疗中晚期肝细胞肝癌的临床疗效及安全性分析. 实用医院临床杂志, 2022, 19(1): 55-59.
18.	颜羽西, 孙沛达, 李莹. 肝动脉化疗栓塞术联合仑伐替尼治疗中晚期肝癌的临床效果. 名医, 2022(19): 165-167.
19.	董龙科, 江昊. 肝动脉化疗栓塞联合仑伐替尼靶向治疗中晚期肝细胞癌的临床效果. 临床医学研究与实践, 2022, 7(1): 42-45.
20.	Fu Z, Li X, Zhong J, et al. Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study. Hepatol Int, 2021, 15(3): 663-675.
21.	Xie QY, Huang LP, Gao FW, et al. Efficacy of lenvatinib combined with sequential transarterial chemoembolization for primary hepatocellular carcinoma and the effects on serum basic fibroblast growth factor and vascular endothelial growth factor. Front Pharmacol, 2022, 13: 965770.
22.	Chen YX, Zhang JX, Zhou CG, et al. Comparison of the efficacy and safety of transarterial chemoembolization with or without lenvatinib for unresectable hepatocellular carcinoma: a retrospective propensity score-matched analysis. J Hepatocell Carcinoma, 2022, 9: 685-694.
23.	党之俊, 温树伟, 赵玉山, 等. CalliSpheres载药栓塞微球联合仑伐替尼治疗原发性肝癌的效果及安全性分析. 中国临床实用医学, 2021, 12(2): 43-46.
24.	Villarruel-Melquiades F, Mendoza-Garrido ME, García-Cuellar CM, et al. Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma. World J Gastroenterol, 2023, 29(17): 2571-2599.
25.	European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol, 2018, 69(1): 182-236.
26.	Brown ZJ, Tsilimigras DI, Ruff SM, et al. Management of hepatocellular carcinoma: a review. JAMA Surg, 2023, 158(4): 410-420.
27.	Liu R, Zhu L, Yu C, et al. Quantitative evaluation of the compatibility effects of aidi injection on the treatment of hepatocellular carcinoma using targeted metabolomics: a new strategy on the mechanism study of an anticancer compound in traditional Chinese medicine. World J Tradit Chin Med, 2021, 7(1): 111-119.
28.	Moon H, Ro SW. MAPK/ERK signaling pathway in hepatocellular carcinoma. Cancers (Basel), 2021, 13(12): 3026.
29.	Jindal A, Thadi A, Shailubhai K. Hepatocellular carcinoma: etiology and current and future drugs. J Clin Exp Hepatol, 2019, 9(2): 221-232.
30.	Fan G, Wei X, Xu X. Is the era of sorafenib over? A review of the literature. Ther Adv Med Oncol, 2020, 12: 1758835920927602. doi: 10.1177/1758835920927602.
31.	宋岩. 索拉非尼与仑伐替尼肝癌一线治疗之争. 肝癌电子杂志, 2018, 5(4): 13-15.
32.	Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet, 2018, 391(10126): 1163-1173.
33.	Chen J, Lai L, Zhou C, et al. Safety, efficacy, and survival of drug-eluting beads-transarterial chemoembolization vs. conventional-transarterial chemoembolization in advanced HCC patients with main portal vein tumor thrombus. Cancer Imaging, 2023, 23(1): 70.
34.	Shi Z, Wang D, Kang T, et al. Comparison of CalliSpheres® microspheres drug-eluting beads and conventional transarterial chemoembolization in hepatocellular carcinoma patients: a randomized controlled trial. Radiol Oncol, 2023, 57(1): 70-79.
35.	Zhou GH, Han J, Sun JH, et al. Efficacy and safety profile of drug-eluting beads transarterial chemoembolization by CalliSpheres® beads in Chinese hepatocellular carcinoma patients. BMC Cancer, 2018, 18(1): 644.
36.	Wu B, Zhou J, Ling G, et al. CalliSpheres drug-eluting beads versus lipiodol transarterial chemoembolization in the treatment of hepatocellular carcinoma: a short-term efficacy and safety study. World J Surg Oncol, 2018, 16(1): 69.
37.	He M, Jiang N, Yin X, et al. Conventional and drug-eluting beads transarterial chemoembolization in patients with unresectable intrahepatic cholangiocarcinoma: a systematic review and pooled analysis. J Cancer Res Clin Oncol, 2023, 149(1): 531-540.
38.	马婧嶔, 杨敏捷, 颜志平. 精细TACE的治疗目标与栓塞终点. 外科理论与实践, 2022, 27(2): 131-133.
39.	Zhang W, Zhou YJ, Yan ZP. Further discussion on the precision TACE therapy. J Interv Radiol, 2021, 30: 971-975.
40.	Wang LZ, Hu XX, Shen XC, et al. Intraarterial lidocaine administration for pain control by water-in-oil technique in transarterial chemoembolization: in vivo and randomized clinical trial. J Hepatocell Carcinoma, 2021, 8: 1221-1232.
41.	Ogasawara S, Chiba T, Ooka Y, et al. A randomized placebo-controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization. Hepatology, 2018, 67(2): 575-585.
42.	Iwamoto H, Suzuki H, Shimose S, et al. Weekends-off lenvatinib for unresectable hepatocellular carcinoma improves therapeutic response and tolerability toward adverse events. Cancers (Basel), 2020, 12(4): 1010.
43.	Okubo H, Ando H, Ishizuka K, et al. Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma. PLoS One, 2020, 15(3): e0229772.

1. Ferlay JEM, Lam F, Colombet M, et al. Global cancer observatory: cancer today. Lyon: International Agency for Research on Cancer, 2020.https://gco.iarc.fr/today (accessed Feb 27, 2021).
2. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers, 2021, 7(1): 6.
3. Garg T, Shrigiriwar A, Habibollahi P, et al. Intraarterial therapies for the management of hepatocellular carcinoma. Cancers (Basel), 2022, 14(14): 3351.
4. Zou X, Xu Q, You R, et al. Efficacy and safety of TACE combined with regorafenib plus PD-1 inhibitor in the treatment of hepatocellular carcinoma after sorafenib resistance. J Hepatocell Carcinoma, 2023, 10: 267-279.
5. Watanabe T, Koyama N. Preclinical study for antitumor mechanism of lenvatinib and clinical studies for hepatocellular carcinoma. Nihon Yakurigaku Zasshi, 2019, 153(5): 242-248.
6. Mei Z, Gao X, Pan C, et al. Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1⁺ CD8⁺ T cells in HCC via blocking VEGFR2. Cancer Sci, 2023, 114(4): 1284-1296.
7. 朱孟超, 张庆桥, 徐浩, 等. CalliSpheres载药微球治疗原发性肝癌并发肝脓肿4例分析. 介入放射学杂志, 2020, 29(9): 939-941.
8. 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版). 中国实用外科杂志, 2022, 42(3): 241-273.
9. 张凤琦, 翁凌凌. 仑伐替尼联合肝动脉化疗栓塞术对中晚期肝癌患者的影响. 中外医学研究, 2022, 20(31): 33-37.
10. 张萌, 沙金平, 高毅, 等. 仑伐替尼联合肝癌介入化疗栓塞术在中晚期肝癌患者中的应用. 中西医结合肝病杂志, 2022, 32(3): 275-276.
11. 钟明艳, 冷幸新, 刘波, 等. 乐伐替尼联合TACE治疗不可手术切除原发性肝癌的临床研究. 江西医药, 2022, 57(1): 20-23.
12. 冯锦荣, 何沙, 陈鹏贻, 等. 经导管肝动脉化疗栓塞联合仑伐替尼治疗对晚期肝癌患者肿瘤坏死体积及并发症的影响. 中文科技期刊数据库(引文版)医药卫生, 2022(12): 43-46.
13. 李冰, 马南, 杨胜楠, 等. 仑伐替尼联合经导管动脉栓塞化疗治疗老年原发性肝癌的疗效. 癌症进展, 2022, 20(11): 1121-1124.
14. 刘耀鸿, 林宜圣, 杨荣焕, 等. 仑伐替尼联合肝动脉化疗栓塞术对中晚期原发性肝癌患者近期疗效、T淋巴细胞免疫功能及预后的影响. 临床误诊误治, 2022, 35(7): 60-63.
15. 艾宁, 杨凯, 王永中, 等. 经肝动脉灌注化疗栓塞术联合甲磺酸仑伐替尼在中晚期肝癌患者中的应用. 中华实验外科杂志, 2022, 39(5): 938-940.
16. 王洪云. 甲磺酸仑伐替尼联合TACE治疗中晚期原发性肝癌的临床效果及安全性分析. 中国医学创新, 2020, 17(31): 6-9.
17. 刘娟, 廖豪杰, 袁国盛, 等. 肝动脉化疗栓塞术联合仑伐替尼治疗中晚期肝细胞肝癌的临床疗效及安全性分析. 实用医院临床杂志, 2022, 19(1): 55-59.
18. 颜羽西, 孙沛达, 李莹. 肝动脉化疗栓塞术联合仑伐替尼治疗中晚期肝癌的临床效果. 名医, 2022(19): 165-167.
19. 董龙科, 江昊. 肝动脉化疗栓塞联合仑伐替尼靶向治疗中晚期肝细胞癌的临床效果. 临床医学研究与实践, 2022, 7(1): 42-45.
20. Fu Z, Li X, Zhong J, et al. Lenvatinib in combination with transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma (uHCC): a retrospective controlled study. Hepatol Int, 2021, 15(3): 663-675.
21. Xie QY, Huang LP, Gao FW, et al. Efficacy of lenvatinib combined with sequential transarterial chemoembolization for primary hepatocellular carcinoma and the effects on serum basic fibroblast growth factor and vascular endothelial growth factor. Front Pharmacol, 2022, 13: 965770.
22. Chen YX, Zhang JX, Zhou CG, et al. Comparison of the efficacy and safety of transarterial chemoembolization with or without lenvatinib for unresectable hepatocellular carcinoma: a retrospective propensity score-matched analysis. J Hepatocell Carcinoma, 2022, 9: 685-694.
23. 党之俊, 温树伟, 赵玉山, 等. CalliSpheres载药栓塞微球联合仑伐替尼治疗原发性肝癌的效果及安全性分析. 中国临床实用医学, 2021, 12(2): 43-46.
24. Villarruel-Melquiades F, Mendoza-Garrido ME, García-Cuellar CM, et al. Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma. World J Gastroenterol, 2023, 29(17): 2571-2599.
25. European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol, 2018, 69(1): 182-236.
26. Brown ZJ, Tsilimigras DI, Ruff SM, et al. Management of hepatocellular carcinoma: a review. JAMA Surg, 2023, 158(4): 410-420.
27. Liu R, Zhu L, Yu C, et al. Quantitative evaluation of the compatibility effects of aidi injection on the treatment of hepatocellular carcinoma using targeted metabolomics: a new strategy on the mechanism study of an anticancer compound in traditional Chinese medicine. World J Tradit Chin Med, 2021, 7(1): 111-119.
28. Moon H, Ro SW. MAPK/ERK signaling pathway in hepatocellular carcinoma. Cancers (Basel), 2021, 13(12): 3026.
29. Jindal A, Thadi A, Shailubhai K. Hepatocellular carcinoma: etiology and current and future drugs. J Clin Exp Hepatol, 2019, 9(2): 221-232.
30. Fan G, Wei X, Xu X. Is the era of sorafenib over? A review of the literature. Ther Adv Med Oncol, 2020, 12: 1758835920927602. doi: 10.1177/1758835920927602.
31. 宋岩. 索拉非尼与仑伐替尼肝癌一线治疗之争. 肝癌电子杂志, 2018, 5(4): 13-15.
32. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet, 2018, 391(10126): 1163-1173.
33. Chen J, Lai L, Zhou C, et al. Safety, efficacy, and survival of drug-eluting beads-transarterial chemoembolization vs. conventional-transarterial chemoembolization in advanced HCC patients with main portal vein tumor thrombus. Cancer Imaging, 2023, 23(1): 70.
34. Shi Z, Wang D, Kang T, et al. Comparison of CalliSpheres® microspheres drug-eluting beads and conventional transarterial chemoembolization in hepatocellular carcinoma patients: a randomized controlled trial. Radiol Oncol, 2023, 57(1): 70-79.
35. Zhou GH, Han J, Sun JH, et al. Efficacy and safety profile of drug-eluting beads transarterial chemoembolization by CalliSpheres® beads in Chinese hepatocellular carcinoma patients. BMC Cancer, 2018, 18(1): 644.
36. Wu B, Zhou J, Ling G, et al. CalliSpheres drug-eluting beads versus lipiodol transarterial chemoembolization in the treatment of hepatocellular carcinoma: a short-term efficacy and safety study. World J Surg Oncol, 2018, 16(1): 69.
37. He M, Jiang N, Yin X, et al. Conventional and drug-eluting beads transarterial chemoembolization in patients with unresectable intrahepatic cholangiocarcinoma: a systematic review and pooled analysis. J Cancer Res Clin Oncol, 2023, 149(1): 531-540.
38. 马婧嶔, 杨敏捷, 颜志平. 精细TACE的治疗目标与栓塞终点. 外科理论与实践, 2022, 27(2): 131-133.
39. Zhang W, Zhou YJ, Yan ZP. Further discussion on the precision TACE therapy. J Interv Radiol, 2021, 30: 971-975.
40. Wang LZ, Hu XX, Shen XC, et al. Intraarterial lidocaine administration for pain control by water-in-oil technique in transarterial chemoembolization: in vivo and randomized clinical trial. J Hepatocell Carcinoma, 2021, 8: 1221-1232.
41. Ogasawara S, Chiba T, Ooka Y, et al. A randomized placebo-controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization. Hepatology, 2018, 67(2): 575-585.
42. Iwamoto H, Suzuki H, Shimose S, et al. Weekends-off lenvatinib for unresectable hepatocellular carcinoma improves therapeutic response and tolerability toward adverse events. Cancers (Basel), 2020, 12(4): 1010.
43. Okubo H, Ando H, Ishizuka K, et al. Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma. PLoS One, 2020, 15(3): e0229772.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Efficacy and safety of transcatheter arterial chemoembolization in combination with lenvatinib in treatment of intermediate and advanced primary liver cancer：a meta-analysis

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