Systemic Therapy for Hepatocellular Carcinoma: 2017 Update

Oncology (Switzerland)

Volumn 93, Issue 1, 2017, Pages 135-146

  Kudo, Masatoshi ^a  

^a KINKI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Hepatic arterial infusion chemotherapy; Immune checkpoint inhibitor; Molecular targeted therapy; Systemic therapy

Indexed keywords

ANTIBODY; BRIVANIB; CABOZANTINIB; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4 ANTIBODY; ERLOTINIB; EVEROLIMUS; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; LENVATINIB; LINIFANIB; NIVOLUMAB; ORANTINIB; PEMBROLIZUMAB; PERETINOIN; PROGRAMMED DEATH 1 ANTIBODY; PROGRAMMED DEATH LIGAND 1 ANTIBODY; RAMUCIRUMAB; REGORAFENIB; SORAFENIB; SUNITINIB; TIVANTINIB; UNCLASSIFIED DRUG; YTTRIUM 90;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RECURRENCE; CANCER SURGERY; CANCER SURVIVAL; CHEMOEMBOLIZATION; DRUG APPROVAL; DRUG EFFICACY; DRUG TREATMENT FAILURE; HUMAN; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; MOLECULARLY TARGETED THERAPY; PRIORITY JOURNAL; RADIOEMBOLIZATION; SYSTEMIC THERAPY; TUMOR ABLATION; ANIMAL; LIVER TUMOR; PROCEDURES; TRENDS;

ANIMALS; CARCINOMA, HEPATOCELLULAR; HUMANS; LIVER NEOPLASMS; MOLECULAR TARGETED THERAPY;

EID: 85038641656     PISSN: 00302414     EISSN: 14230232     Source Type: Journal    
DOI: 10.1159/000481244     Document Type: Article

References (72)

1. Kudo M: Immune checkpoint blockade in hepatocellular carcinoma. Liver Cancer 2015;4:201-207.
2. Kudo M: Molecular targeted therapy for hepatocellular carcinoma: where are we now? Liver Cancer 2015;4:I-VII.
3. Kudo M: Regorafenib as second-line systemic therapy may change the treatment strategy and management paradigm for hepatocellular carcinoma. Liver Cancer 2016;5:235-244.
4. Zhang B, Finn RS: Personalized clinical trials in hepatocellular carcinoma based on biomarker selection. Liver Cancer 2016;5:221-232.
5. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004;64:7099-7109.
6. Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D, et al. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol 2007;59:561-574.
7. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-390.
8. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25-34.
9. Kudo M: Locoregional therapy for hepatocellular carcinoma. Liver Cancer 2015;4:163-164.
10. Kang TW, Rhim H: Recent advances in tumor ablation for hepatocellular carcinoma. Liver Cancer 2015;4:176-187.
11. Lencioni R, de Baere T, Martin RC, Nutting CW, Narayanan G: Image-guided ablation of malignant liver tumors: recommendations for clinical validation of novel thermal and non-thermal technologies-a Western perspective. Liver Cancer 2015;4:208-214.
12. Kudo M, Izumi N, Sakamoto M, Matsuyama Y, Ichida T, Nakashima O, et al. Survival analysis over 28 years of 173,378 patients with hepatocellular carcinoma in Japan. Liver Cancer 2016;5:190-197.
13. Ho MC, Hasegawa K, Chen XP, Nagano H, Lee YJ, Chau GY, et al. Surgery for intermediate and advanced hepatocellular carcinoma: a consensus report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014). Liver Cancer 2016;5:245-256.
14. Kudo M: Surveillance, diagnosis, treatment, and outcome of liver cancer in Japan. Liver Cancer 2015;4:39-50.
15. Poon RT, Cheung TT, Kwok PC, Lee AS, Li TW, Loke KL, et al. Hong Kong consensus recommendations on the management of hepatocellular carcinoma. Liver Cancer 2015;4:51-69.
16. Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol 2015;16:1344-1354.
17. Nakamura N, Shidoji Y, Yamada Y, Hatakeyama H, Moriwaki H, Muto Y: Induction of apoptosis by acyclic retinoid in the human hepatoma-derived cell line, HuH-7. Biochem Biophys Res Commun 1995;207:382-388.
18. Yasuda I, Shiratori Y, Adachi S, Obora A, Takemura M, Okuno M, et al. Acyclic retinoid induces partial differentiation, down-regulates telomerase reverse transcriptase mRNA expression and telomerase activity, and induces apoptosis in human hepatoma-derived cell lines. J Hepatol 2002;36:660-671.
19. Okita K, Izumi N, Matsui O, Tanaka K, Kaneko S, Moriwaki H, et al. Peretinoin after curative therapy of hepatitis C-related hepatocellular carcinoma: a randomized double-blind placebo-controlled study. J Gastroenterol 2015;50:191-202.
20. Tsurusaki M, Murakami T: Surgical and locoregional therapy of HCC: TACE. Liver Cancer 2015;4:165-175.
21. Arizumi T, Ueshima K, Minami T, Kono M, Chishina H, Takita M, et al. Effectiveness of sorafenib in patients with transcatheter arterial chemoembolization (TACE) refractory and intermediate-stage hepatocellular carcinoma. Liver Cancer 2015;4:253-262.
22. Lencioni R, Llovet JM, Han G, Tak WY, Yang J, Guglielmi A, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol 2016;64:1090-1098.
23. Meyer T, Fox R, Ma YT, Ross PJ, James MW, Sturgess R, Stubbs C, Stocken DD, Wall L, Watkinson A, Hacking N, Evans TRJ, Collins P, Hubner RA, Cunningham D, Primrose JN, Johnson PJ, Palmer DH: Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol 2017;2:565-575.
24. Arizumi T, Ueshima K, Iwanishi M, Minami T, Chishina H, Kono M, et al. The overall survival of patients with hepatocellular carcinoma correlates with the newly defined time to progression after transarterial chemoembolization. Liver Cancer 2017;6:227-235.
25. Hoekman K: SU6668, a multitargeted angiogenesis inhibitor. Cancer J 2001;7(suppl 3): S134-S138.
26. Park JW, Cheng AL, Kudo M, Park JH, Liang CP, Hidaka H, et al. A randomized, double-blind, placebo-controlled phase III trial of TSU-68 (orantinib) combined with transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma. J Hepatol 2015;62(suppl 1):abstract G06.
27. Kudo M, Han G, Finn RS, Poon RT, Blanc JF, Yan L, et al. Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: a randomized phase III trial. Hepatology 2014;60:1697-1707.
28. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9:327-337.
29. Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013;31:4067-4075.
30. Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol 2013;31:3517-3524.
31. Cainap C, Qin S, Huang WT, Chung IJ, Pan H, Cheng Y, et al. Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol 2015;33:172-179.
32. Zhu AX, Rosmorduc O, Evans TR, Ross PJ, Santoro A, Carrilho FJ, et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2015;33:559-566.
33. Yamamoto Y, Matsui J, Matsushima T, Obaishi H, Miyazaki K, Nakamura K, et al. Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage. Vasc Cell 2014;6:18.
34. Ikeda K, Kudo M, Kawazoe S, Osaki Y, Ikeda M, Okusaka T, et al. Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma. J Gastroenterol 2017;52:512-519.
35. Kudo M, Finn R, Qin S, Han K-H, Ikeda K, Piscaglia F, Baron A, Park J-W, 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 A-L: A randomised phase 3 trial of lenvatinib vs. sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma. Lancet 2017, in press.
36. Khajornjiraphan N, Thu NA, Chow PK: Yttrium-90 microspheres: a review of its emerging clinical indications. Liver Cancer 2015;4:6-15.
37. Edeline J, Gilabert M, Garin E, Boucher E, Raoul JL: Yttrium-90 microsphere radioembolization for hepatocellular carcinoma. Liver Cancer 2015;4:16-25.
38. Cucchetti A, Cappelli A, Ercolani G, Mosconi C, Cescon M, Golfieri R, et al. Selective internal radiation therapy (SIRT) as conversion therapy for unresectable primary liver malignancies. Liver Cancer 2016;5:303-311.
39. Vilgrain V, et al. SARAH trial: Sorafenib vs Radioembolization in Advanced Hepatocellular Carcinoma. EASL 2017, GS012.
40. Chow PK, et al. Phase III multi-centre open-label randomized controlled trial of selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma: the SIRveNIB study. J Clin Oncol 2017;35(suppl):abstract 4002.
41. Obi S, Sato S, Kawai T: Current status of hepatic arterial infusion chemotherapy. Liver Cancer 2015;4:188-199.
42. Lin CC, Hung CF, Chen WT, Lin SM: Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein thrombosis: impact of early response to 4 weeks of treatment. Liver Cancer 2015;4:228-240.
43. Ueshima K, Kudo M, Tanaka M, Kumada T, Chung H, Hagiwara S, et al. Phase I/II study of sorafenib in combination with hepatic arterial infusion chemotherapy using low-dose cisplatin and 5-fluorouracil. Liver Cancer 2015;4:263-273.
44. Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, et al. Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol 2013;31:3509-3516.
45. Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 2014;312:57-67.
46. Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol 2013;14:55-63.
47. Rimassa L, Abbadessa G, Personeni N, Porta C, Borbath I, Daniele B, et al. Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib. Oncotarget 2016;7:72622-72633.
48. Rimassa L, Assenat E, Peck-Radosavljevic M, Zagonel V, Pracht M, Rota-Caremoli E, et al. Second-line tivantinib vs placebo in patients with MET-high hepatocellular carcinoma: results of the METIV-HCC phase 3 trial. ASCO Annual Meeting '17 (abstract 4000). https://www.arqule.com/wp-content/uploads/Tivantinib-METIV-HCC-Phase-3-trial-ASCO-2017.pdf.
49. 1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 2010;28:780-787.
50. Zhu AX, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 2015;16:859-870.
51. Kudo M, Hatano E, Ohkawa S, Fujii H, Masumoto A, Furuse J, et al. Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial. J Gastroenterol 2017;52:494-503.
52. Kudo M, Moriguchi M, Numata K, Hidaka H, Tanaka H, Ikeda M, et al. S-1 versus placebo in patients with sorafenib-refractory advanced hepatocellular carcinoma (S-CUBE): a randomised, double-blind, multicentre, phase 3 trial. Lancet Gastroenterol Hepatol 2017;2:407-417.
53. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schütz G, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011;129:245-255.
54. Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;389:56-66.
55. Villanueva A: Rethinking future development of molecular therapies in hepatocellular carcinoma: a bottom-up approach. J Hepatol 2013;59:392-395.
56. Lim HY, Heo J, Choi HJ, Lin CY, Yoon JH, Hsu C, et al. A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma. Clin Cancer Res 2014;20:5976-5985.
57. Kitai S, Kudo M, Nishida N, Izumi N, Sakamoto M, Matsuyama Y, et al. Survival benefit of locoregional treatment for hepatocellular carcinoma with advanced liver cirrhosis. Liver Cancer 2016;5:175-189.
58. Nishikawa H, Kita R, Kimura T, Ohara Y, Takeda H, Sakamoto A, et al. Clinical efficacy of non-transplant therapies in patients with hepatocellular carcinoma with Child-Pugh C liver cirrhosis. Anticancer Res 2014;34:3039-3044.
59. Nouso K, Kokudo N, Tanaka M, Kuromatsu R, Nishikawa H, Toyoda H, et al. Treatment of hepatocellular carcinoma with Child-Pugh C cirrhosis. Oncology 2014;87(suppl 1):99-103.
60. Nouso K, Ito Y, Kuwaki K, Kobayashi Y, Nakamura S, Ohashi Y, et al. Prognostic factors and treatment effects for hepatocellular carcinoma in Child C cirrhosis. Br J Cancer 2008;98:1161-1165.
61. Kudo M, Osaki Y, Matsunaga T, Kasugai H, Oka H, Seki T: Hepatocellular carcinoma in Child-Pugh C cirrhosis: prognostic factors and survival benefit of nontransplant treatments. Dig Dis 2013;31:490-498.
62. Terashima T, Yamashita T, Takata N, Nakagawa H, Toyama T, Arai K, et al. Post-progression survival and progression-free survival in patients with advanced hepatocellular carcinoma treated by sorafenib. Hepatol Res 2016;46:650-656.
63. Ishida Y, Agata Y, Shibahara K, Honjo T: Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 1992;11:3887-3895.
64. Okazaki T, Honjo T: PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol 2007;19:813-824.
65. Krummel MF, Allison JP: CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995;182:459-465.
66. Leach DR, Krummel MF, Allison JP: Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996;271:1734-1736.
67. El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017;389:2492-2502.
68. Crocenzi TS, El-Khoueiry AB, Yau TC, Melero I, Sangro B, Kudo M, et al. Nivolumab (nivo) in sorafenib (sor)-naive and-experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate040 Study. J Clin Oncol 2017;35:abstract 4013.
69. Finn RS, Chan SL, Zhu AX, et al. KEYNOTE: Randomized phase III study of pembrolizumab versus best supportive care for second-line advanced hepatocellular carcinoma. J Clin Oncol 2017;35(suppl):abstr TPS4143.
70. Taylor M, Dutcus CE, Schmidt E, Bagulho T, Li D, Shumaker R, et al. A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEM) in patients with selected solid tumors. Ann Oncol 2016;27:266-295, abstract 776PD.
71. FDA: FDA approves first cancer treatment for any solid tumor with a specific genetic feature. May 23, 2017. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm.
72. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509-2520.