Neoadjuvant Combination Therapy of Lenvatinib and TACE for Transplant-Eligible Large Hepatocellular Carcinoma Patients

Summary

This study will examine the effects of a six-month regimen of neoadjuvant lenvatinib in combination with transcatheter arterial chemoembolization (TACE) prior to liver transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan Criteria. Clinical, outcomes, and exploratory data will be compared to a matched, retrospective cohort.

Timeline

Start

2022-06-20

Primary completion

2026-06-30

Completion

2027-12-30

Publications

• Background Hsiao P, Hsieh KC, Chen YS, Hsu CC, Lo GH, Li YC, Hsieh PM, Lin HY, Wu TC, Yeh JH, Lin CW. Sorafenib with concurrent multiple-line therapies improves overall survival in advanced stage hepatocellular carcinoma. Medicine (Baltimore). 2019 Jun;98(25):e16074. doi: 10.1097/MD.0000000000016074.
• Background Wu FX, Chen J, Bai T, Zhu SL, Yang TB, Qi LN, Zou L, Li ZH, Ye JZ, Li LQ. The safety and efficacy of transarterial chemoembolization combined with sorafenib and sorafenib mono-therapy in patients with BCLC stage B/C hepatocellular carcinoma. BMC Cancer. 2017 Sep 12;17(1):645. doi: 10.1186/s12885-017-3545-5.
• Background Zhang W, Jin K, Wang F, Zhangyuan G, Yu W, Liu Y, Zhang H, Zhang P, Sun B. Differences in the prognostic value of tumor size on hepatocellular cancer-specific survival stratified by gender in a SEER population-based study. United European Gastroenterol J. 2019 Aug;7(7):933-941. doi: 10.1177/2050640619845602. Epub 2019 Apr 24.
• Background White DL, Thrift AP, Kanwal F, Davila J, El-Serag HB. Incidence of Hepatocellular Carcinoma in All 50 United States, From 2000 Through 2012. Gastroenterology. 2017 Mar;152(4):812-820.e5. doi: 10.1053/j.gastro.2016.11.020. Epub 2016 Nov 23.
• Background Lenvima [Package Insert]. Eisai R&D Management Co., Ltd. http://www.lenvima.com/pdfs/prescribinginformation. pdf. Published 2020. Accessed June 12, 2020.
• Background Yang JD, Larson JJ, Watt KD, Allen AM, Wiesner RH, Gores GJ, Roberts LR, Heimbach JA, Leise MD. Hepatocellular Carcinoma Is the Most Common Indication for Liver Transplantation and Placement on the Waitlist in the United States. Clin Gastroenterol Hepatol. 2017 May;15(5):767-775.e3. doi: 10.1016/j.cgh.2016.11.034. Epub 2016 Dec 21.
• Background Daoud A, Teeter L, Ghobrial RM, Graviss EA, Mogawer S, Sholkamy A, El-Shazli M, Gaber AO. Transplantation for Hepatocellular Carcinoma: Is There a Tumor Size Limit? Transplant Proc. 2018 Dec;50(10):3577-3581. doi: 10.1016/j.transproceed.2018.04.038. Epub 2018 Apr 18.
• Background Bharat A, Brown DB, Crippin JS, Gould JE, Lowell JA, Shenoy S, Desai NM, Chapman WC. Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival. J Am Coll Surg. 2006 Oct;203(4):411-20. doi: 10.1016/j.jamcollsurg.2006.06.016. Epub 2006 Aug 17.
• Background SEER stats. Liver and intrahepatic bile duct cancer. U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Cancer Stat Facts Web site. https://seer.cancer.gov/statfacts/html/livibd.html. Published 2019. Accessed December 8, 2019.
• Background Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996 Mar 14;334(11):693-9. doi: 10.1056/NEJM199603143341104.
• Background Young S, Sanghvi T, Lake JJ, Rubin N, Golzarian J. Predicting post-transarterial chemoembolization outcomes: A comparison of direct and total bilirubin serums levels. Diagn Interv Imaging. 2020 Jun;101(6):355-364. doi: 10.1016/j.diii.2019.12.006. Epub 2020 Jan 13.
• Background Lee S, Kang JH, Kim DY, Ahn SH, Park JY, Kim BK, Kim SU, Han KH. Prognostic factors of sorafenib therapy in hepatocellular carcinoma patients with failure of transarterial chemoembolization. Hepatol Int. 2017 May;11(3):292-299. doi: 10.1007/s12072-017-9792-3. Epub 2017 Mar 21.
• Background Matsuki M, Hoshi T, Yamamoto Y, Ikemori-Kawada M, Minoshima Y, Funahashi Y, Matsui J. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 2018 Jun;7(6):2641-2653. doi: 10.1002/cam4.1517. Epub 2018 May 7.
• Background Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.
• Background Victor DW 3rd, Monsour HP Jr, Boktour M, Lunsford K, Balogh J, Graviss EA, Nguyen DT, McFadden R, Divatia MK, Heyne K, Ankoma-Sey V, Egwim C, Galati J, Duchini A, Saharia A, Mobley C, Gaber AO, Ghobrial RM. Outcomes of Liver Transplantation for Hepatocellular Carcinoma Beyond the University of California San Francisco Criteria: A Single-center Experience. Transplantation. 2020 Jan;104(1):113-121. doi: 10.1097/TP.0000000000002835.
• Background Highlights of prescribing information: Lenvima. In:2020.
• Background Oligane HC, Xing M, Kim HS. Effect of Bridging Local-Regional Therapy on Recurrence of Hepatocellular Carcinoma and Survival after Orthotopic Liver Transplantation. Radiology. 2017 Mar;282(3):869-879. doi: 10.1148/radiol.2016160288. Epub 2016 Sep 27.
• Background Kudo M. Proposal of Primary Endpoints for TACE Combination Trials with Systemic Therapy: Lessons Learned from 5 Negative Trials and the Positive TACTICS Trial. Liver Cancer. 2018 Sep;7(3):225-234. doi: 10.1159/000492535. Epub 2018 Aug 23. No abstract available.
• Background Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010 Feb;30(1):52-60. doi: 10.1055/s-0030-1247132. Epub 2010 Feb 19.
• Background Hastie T, Tibshirani R, Wainwright M. Statistical Learning with Sparsity: The Lasso and Generalizations. Boca Raton, FL: CRC Press; 2015.

Drugs

Indications