Exploration of safety and efficacy of lenvatinib in combination with TACE and PD-1 antibody in treatment of recurrent liver cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

AN Wen ^1,2 , SHEN Junyi ¹ , ZHU Xinrui ³ , ZHANG Xiaoyun ¹ , PENG Wei ¹ , LIU Chang ¹ , LI Qiu ⁴ , CHEN Weixia ⁵ , LU Wusheng ¹ , YAN Lünan ¹ ,  WEN Tianfu ¹

1. Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. Second Department of Hepatobiliary Surgery, Wulanchabu Central Hospital, Wulanchabu, Inner Mongolia Autonomous Region 012000, P. R. China;
3. Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu 213000, P. R. China;
4. Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
5. Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

WEN Tianfu, Email: wentianfu@scu.edu.cn

Keywords：

recurrent liver cancer; lenvatinib; transarterial chemoembolization; programmed death-1 antibody

DOI：

10.7507/1007-9424.202208020

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Objective To explore the safety and efficacy of lenvatinib in combination with transarterial chemoembolization (TACE) and programmed death receptor 1 (PD-1) antibody in the treatment of recurrent liver cancer. Method The clinical data of 22 patients with unresectable recurrent liver cancer admitted to Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University and received the conversion therapy of lenvatinib+TACE+PD-1 antibody between January 2019 and January 2022 were retrospectively analyzed. Results All 22 patients experienced some degree of adverse events, with a grade 3 adverse event rate of 18.2% (4/22) and no grade 4 or higher adverse events. At 4 months of treatment, according to the modified response evaluation criteria solid tumors (mRECIST), 2 cases were in complete response (CR), 5 cases were in partial response (PR), and 6 cases were in stable disease (SD), 9 cases were in progressive disease (PD), and the objective response (CR+PR) rate (ORR) was 31.8% (7/22). At the last follow-up, there was 1 case in CR, 5 cases in PR, 1 case in SD, and 15 cases in PD, with an ORR of 27.3% (6/22). The 1-year overall survival (OS) rate was 83.8% and the 1-year progression-free survival (PFS) rate was 38.2%. In the subgroup analysis, the 1-year OS rate for patients with recurrent liver cancer with intrahepatic lesions (n=16) only was 86.2% [95%CI (77.1%, 95.3%)], the 1-year PFS rate was 46.9% [95%CI (34.0%, 59.8%)], and the ORR based on mRECIST criteria was 43.8% (7/16). Patients with intrahepatic combined with extrahepatic lesions (n=6) had a 1-year OS rate of 75.0% [95%CI (53.3%, 96.7%)] and a 1-year PFS rate of 16.7% [95%CI (15.0%, 31.9%)], and the ORR based on mRECIST criteria was 0% (0/6). There were no significant differences in OS (P=0.864) and PFS (P=0.125) between the two subgroups. The ORR of intrahepatic combined with extrahepatic lesions group was worse compared to the intrahepatic lesion group (P=0.049). Conclusion Lenvatinib in combination with TACE and PD-1 antibody is safe and effective in the treatment of unresectable recurrent liver cancer, but there are still many issues that deserve further exploration.

Citation： AN Wen, SHEN Junyi, ZHU Xinrui, ZHANG Xiaoyun, PENG Wei, LIU Chang, LI Qiu, CHEN Weixia, LU Wusheng, YAN Lünan, WEN Tianfu. Exploration of safety and efficacy of lenvatinib in combination with TACE and PD-1 antibody in treatment of recurrent liver cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(10): 1289-1295. doi: 10.7507/1007-9424.202208020 Copy

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
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6.	Liang HH, Chen MS, Peng ZW, et al. Percutaneous radiofrequency ablation versus repeat hepatectomy for recurrent hepatocellular carcinoma: a retrospective study. Ann Surg Oncol, 2008, 15(12): 3484-3493.
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8.	Song KD, Lim HK, Rhim H, et al. Repeated hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma after hepatic resection: a propensity score matching study. Radiology, 2015, 275(2): 599-608.
9.	Poon RT, Fan ST, Lo CM, et al. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg, 1999, 229(2): 216-222.
10.	Cheng YC, Chen TW, Fan HL, et al. Transarterial chemoembolization for intrahepatic multiple recurrent HCC after liver resection or transplantation. Ann Transplant, 2014, 19: 309-316.
11.	Zhang X, Li C, Wen T, et al. Appropriate treatment strategies for intrahepatic recurrence after curative resection of hepatocellular carcinoma initially within the Milan criteria: according to the recurrence pattern. Eur J Gastroenterol Hepatol, 2015, 27(8): 933-940.
12.	Jin YJ, Lee JW, Lee OH, et al. Transarterial chemoembolization versus surgery/radiofrequency ablation for recurrent hepatocellular carcinoma with or without microvascular invasion. J Gastroenterol Hepatol, 2014, 29(5): 1056-1064.
13.	Sun Y, Wu L, Zhong Y, et al. Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma. Cell, 2021, 184(2): 404-421. e416. doi: 10.1016/j.cell.2020.11.041.
14.	Hassan EA, Ahmed EH, Nafee AM, et al. Regulatory T cells, IL10 and IL6 in HCV related hepatocellular carcinoma after transarterial chemoembolization (TACE). Egypt J Immunol, 2019, 26(1): 69-78.
15.	Kinter AL, Godbout EJ, McNally JP, et al. The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J Immunol, 2008, 181(10): 6738-6746.
16.	张晓赟, 朱心睿, 彭伟, 等. 经肝动脉化疗栓塞+仑伐替尼+PD-1单抗在中晚期不可切除肝癌转化切除中的安全性和有效性的前瞻性队列研究: 初步报告. 中国普外基础与临床杂志, 2022, 29(1): 39-45.
17.	Zhao Y, Cai G, Zhou L, et al. Transarterial chemoembolization in hepatocellular carcinoma with vascular invasion or extrahepatic metastasis: a systematic review. Asia Pac J Clin Oncol, 2013, 9(4): 357-364.
18.	Yao W, Xue M, Lu M, et al. Diffuse recurrence of hepatocellular carcinoma after liver resection: transarterial chemoembolization (TACE) combined with sorafenib versus TACE monotherapy. Front Oncol, 2020, 10: 574668. doi: 10.3389/fonc.2020.574668.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. 《原发性肝癌诊疗规范(2019年版)》编写专家委员会. 原发性肝癌诊疗规范(2019年版). 中国临床医学, 2020, 27(1): 140-156.
3. 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版). 传染病信息, 2020, 33(6): 481-500.
4. Zhang X, Li C, Wen T, et al. Outcomes of salvage liver transplantation and re-resection/radiofrequency ablation for intrahepatic recurrent hepatocellular carcinoma: a new surgical strategy based on recurrence pattern. Dig Dis Sci, 2018, 63(2): 502-514.
5. Zhang X, Li C, Wen T, et al. Treatment for intrahepatic recurrence after curative resection of hepatocellular carcinoma: salvage liver transplantation or re-resection/radiofrequency ablation? A retrospective cohort study. Int J Surg, 2017, 46: 178-185.
6. Liang HH, Chen MS, Peng ZW, et al. Percutaneous radiofrequency ablation versus repeat hepatectomy for recurrent hepatocellular carcinoma: a retrospective study. Ann Surg Oncol, 2008, 15(12): 3484-3493.
7. Wang K, Liu G, Li J, et al. Early intrahepatic recurrence of hepatocellular carcinoma after hepatectomy treated withre-hepatectomy, ablation or chemoembolization: a prospective cohort study. Eur J Surg Oncol, 2015, 41(2): 236-242.
8. Song KD, Lim HK, Rhim H, et al. Repeated hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma after hepatic resection: a propensity score matching study. Radiology, 2015, 275(2): 599-608.
9. Poon RT, Fan ST, Lo CM, et al. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg, 1999, 229(2): 216-222.
10. Cheng YC, Chen TW, Fan HL, et al. Transarterial chemoembolization for intrahepatic multiple recurrent HCC after liver resection or transplantation. Ann Transplant, 2014, 19: 309-316.
11. Zhang X, Li C, Wen T, et al. Appropriate treatment strategies for intrahepatic recurrence after curative resection of hepatocellular carcinoma initially within the Milan criteria: according to the recurrence pattern. Eur J Gastroenterol Hepatol, 2015, 27(8): 933-940.
12. Jin YJ, Lee JW, Lee OH, et al. Transarterial chemoembolization versus surgery/radiofrequency ablation for recurrent hepatocellular carcinoma with or without microvascular invasion. J Gastroenterol Hepatol, 2014, 29(5): 1056-1064.
13. Sun Y, Wu L, Zhong Y, et al. Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma. Cell, 2021, 184(2): 404-421. e416. doi: 10.1016/j.cell.2020.11.041.
14. Hassan EA, Ahmed EH, Nafee AM, et al. Regulatory T cells, IL10 and IL6 in HCV related hepatocellular carcinoma after transarterial chemoembolization (TACE). Egypt J Immunol, 2019, 26(1): 69-78.
15. Kinter AL, Godbout EJ, McNally JP, et al. The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J Immunol, 2008, 181(10): 6738-6746.
16. 张晓赟, 朱心睿, 彭伟, 等. 经肝动脉化疗栓塞+仑伐替尼+PD-1单抗在中晚期不可切除肝癌转化切除中的安全性和有效性的前瞻性队列研究: 初步报告. 中国普外基础与临床杂志, 2022, 29(1): 39-45.
17. Zhao Y, Cai G, Zhou L, et al. Transarterial chemoembolization in hepatocellular carcinoma with vascular invasion or extrahepatic metastasis: a systematic review. Asia Pac J Clin Oncol, 2013, 9(4): 357-364.
18. Yao W, Xue M, Lu M, et al. Diffuse recurrence of hepatocellular carcinoma after liver resection: transarterial chemoembolization (TACE) combined with sorafenib versus TACE monotherapy. Front Oncol, 2020, 10: 574668. doi: 10.3389/fonc.2020.574668.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Exploration of safety and efficacy of lenvatinib in combination with TACE and PD-1 antibody in treatment of recurrent liver cancer

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