Systemic treatment of advanced hepatocellular carcinoma: From disillusions to new horizons

European Journal of Cancer

Volumn 51, Issue 3, 2015, Pages 327-339

  Hollebecque, Antoine ^a   Malka, David ^a   Ferté, Charles ^a   Ducreux, Michel ^a   Boige, Valérie ^a  

^a INSTITUT GUSTAVE ROUSSY   (France)

Author keywords

Drug development; Hepatocellular carcinoma; Molecular biomarkers; Molecular targeted agents; Signalling pathway; Sorafenib; Systemic treatment

Indexed keywords

ANTINEOPLASTIC AGENT; BEVACIZUMAB; BRIVANIB; CABOZANTINIB; CAPECITABINE PLUS OXALIPLATIN; CIXUTUMUMAB; DOVITINIB; DOXORUBICIN; ERLOTINIB; EVEROLIMUS; FLUOROURACIL; GEMCITABINE; LENALIDOMIDE; LENVATINIB; LINIFANIB; LINSITINIB; MAPATUMUMAB; NIVOLUMAB; OXALIPLATIN; PEGARGIMINASE; PEXASTIMOGENE DEVACIREPVEC; RAMUCIRUMAB; REFAMETINIB; REGORAFENIB; SELUMETINIB; SORAFENIB; SUNITINIB; TEMSIROLIMUS; TICILIMUMAB; TIVANTINIB; ANGIOGENESIS INHIBITOR; CARBANILAMIDE DERIVATIVE; NEW DRUG; NICOTINAMIDE;

ADVANCED CANCER; ANOREXIA; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CHRONIC LIVER DISEASE; DRUG CYTOTOXICITY; DRUG ERUPTION; DRUG SAFETY; GASTROINTESTINAL TOXICITY; HEPATIC ENCEPHALOPATHY; HUMAN; LIVER CELL CARCINOMA; LIVER DYSFUNCTION; LIVER FAILURE; NAUSEA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SYSTEMIC THERAPY; TUMOR LYSIS SYNDROME; VOMITING; ADJUVANT CHEMOTHERAPY; ADJUVANT THERAPY; ANALOGS AND DERIVATIVES; CARCINOMA, HEPATOCELLULAR; DISEASE COURSE; LIVER NEOPLASMS; PATHOLOGY; TREATMENT FAILURE;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; CARCINOMA, HEPATOCELLULAR; CHEMOTHERAPY, ADJUVANT; DISEASE PROGRESSION; DRUGS, INVESTIGATIONAL; HUMANS; LIVER NEOPLASMS; NEOADJUVANT THERAPY; NIACINAMIDE; PHENYLUREA COMPOUNDS; TREATMENT FAILURE;

EID: 84922681438     PISSN: 09598049     EISSN: 18790852     Source Type: Journal    
DOI: 10.1016/j.ejca.2014.12.005     Document Type: Article

References (137)

1. A. Jemal, F. Bray, M.M. Center, J. Ferlay, E. Ward, and D. Forman Global cancer statistics CA Cancer J Clin 61 2 2011 69 90
2. C.L. Lai, P.C. Wu, G.C. Chan, A.S. Lok, and H.J. Lin Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial Cancer 62 3 1988 479 483
3. J.M. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, E. Gane, and J.F. Blanc Sorafenib in advanced hepatocellular carcinoma N Engl J Med 359 4 2008 378 390
4. A.L. Cheng, Y.K. Kang, Z. Chen, C.J. Tsao, S. Qin, and J.S. Kim 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 10 1 2009 25 34
5. Y. Chao, C.P. Li, G.Y. Chau, C.P. Chen, K.L. King, and W.Y. Lui Prognostic significance of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin in patients with resectable hepatocellular carcinoma after surgery Ann Surg Oncol 10 4 2003 355 362
6. K.S. Jeng, I.S. Sheen, Y.C. Wang, S.L. Gu, C.M. Chu, and S.C. Shih Prognostic significance of preoperative circulating vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma: a prospective study World J Gastroenterol 10 5 2004 643 648
7. H. Huynh, V.C. Ngo, J. Fargnoli, M. Ayers, K.C. Soo, and H.N. Koong Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma Clin Cancer Res 14 19 2008 6146 6153
8. J.W. Park, R.S. Finn, J.S. Kim, M. Karwal, R.K. Li, and F. Ismail Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma Clin Cancer Res 17 7 2011 1973 1983
9. P.J. Johnson, S. Qin, J.W. Park, R.T. Poon, J.L. Raoul, and P.A. Philip 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 31 28 2013 3
10. Y. Kang, T. Yau, J. Park, E. Boucher, H. Lim, and R. Poon Randomised study of axitinib plus best supportive care versus placebo plus BSC in patients with advanced hepatocellular carcinoma following prior antiangiogenic therapy ESMO Congress 2014 17 2014
11. S. Faivre, E. Raymond, E. Boucher, J. Douillard, H.Y. Lim, and J.S. Kim Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study Lancet Oncol 10 8 2009 794 800
12. D. Koeberle, M. Montemurro, P. Samaras, P. Majno, M. Simcock, and A. Limacher Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06) Oncologist 15 3 2010 285 292
13. A.L. Cheng, Y.K. Kang, D.Y. Lin, J.W. Park, M. Kudo, and S. Qin Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial J Clin Oncol 31 32 2013 4067 4075
14. C. Cainap, S. Qin, W.-T. Huang, I.-J. Chung, H. Pan, and Y. Cheng Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) ASCO Meeting Abstracts 31 4-suppl 2013 249
15. V. Boige, D. Malka, A. Bourredjem, C. Dromain, C. Baey, and N. Jacques Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma Oncologist 17 8 2012 1063 1072
16. A.B. Siegel, E.I. Cohen, A. Ocean, D. Lehrer, A. Goldenberg, and J.J. Knox Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma J Clin Oncol 26 18 2008 2992 2998
17. A.X. Zhu, B. Ryoo, C. Yen, M. Kudo, R. Poon, and D. Pastorelli Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Results from the randomized phase III REACH study ESMO Congress 2014 2014 LBA16
18. J.M. Llovet, T. Decaens, J.L. Raoul, E. Boucher, M. Kudo, and C. Chang 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 31 28 2013 3509 3516
19. C. Hsu, T.S. Yang, T.I. Huo, R.K. Hsieh, C.W. Yu, and W.S. Hwang Vandetanib in patients with inoperable hepatocellular carcinoma: a phase II, randomized, double-blind, placebo-controlled study J Hepatol 56 5 2012 1097 1103
20. S.R. Alberts, J.M. Reid, B.W. Morlan, G.H. Farr Jr., J.K. Camoriano, and D.B. Johnson Gemcitabine and docetaxel for hepatocellular carcinoma: a phase II North Central Cancer Treatment Group clinical trial Am J Clin Oncol 35 5 2012 418 423
21. R.S. Finn, A. Cheng, K. Ikeda, M. Kudo, T. Tamai, and C.E. Ductus A multicenter open-label, phase 3 trial to compare the efficacy and safety of lenvatinib (E7080) versus sorafenib in first-line treatment of subjects with unresectable hepatocellular carcinoma J Clin Oncol 2014 Abstract TPS4153
22. J.M. Llovet Focal gains of VEGFA: candidate predictors of sorafenib response in hepatocellular carcinoma Cancer Cell 25 5 2014 560 562
23. E. Horwitz, I. Stein, M. Andreozzi, J. Nemeth, A. Shoham, and O. Pappo Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment Cancer Discov 4 6 2014 730 743
24. S. Qin, Y. Bai, H.Y. Lim, S. Thongprasert, Y. Chao, and J. Fan Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia J Clin Oncol 31 28 2013 3501 3508
25. G.K. Abou-Alfa, P. Johnson, J.J. Knox, M. Capanu, I. Davidenko, and J. Lacava Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial JAMA 304 19 2010 2154 2160
26. S. Louafi, V. Boige, M. Ducreux, L. Bonyhay, T. Mansourbakht, and T. de Baere Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC): results of a phase II study Cancer 109 7 2007 1384 1390
27. A. Zaanan, N. Williet, M. Hebbar, T.S. Dabakuyo, L. Fartoux, and T. Mansourbakht Gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma: a large multicenter AGEO study J Hepatol 58 1 2013 81 88
28. O. Mir, R. Coriat, P. Boudou-Rouquette, S. Ropert, J.P. Durand, and A. Cessot Gemcitabine and oxaliplatin as second-line treatment in patients with hepatocellular carcinoma pre-treated with sorafenib Med Oncol 29 4 2012 2793 2799
29. A. Patrikidou, I. Sinapi, H. Regnault, F. Fayard, M. Bouattour, and L. Fartoux Gemcitabine and oxaliplatin chemotherapy for advanced hepatocellular carcinoma after failure of anti-angiogenic therapies Invest New Drugs 32 5 2014 1028 1035
30. E. Assenat, V. Boige, S. Thezenas, G.-P. Pageaux, J.-M. Peron, and Y. Becouarn Sorafenib (S) alone versus S combined with gemcitabine and oxaliplatin (GEMOX) in first-line treatment of advanced hepatocellular carcinoma (HCC): final analysis of the randomized phase II GONEXT trial (UNICANCER/FFCD PRODIGE 10 trial) ASCO Meeting Abstracts 31 15-suppl 2013 4028
31. T.C. Yau, F.Y. Cheung, F. Lee, S.P. Choo, H. Wong, and H.C. Toh A multicenter phase II study of sorafenib, capecitabine, and oxaliplatin (SECOX) in patients with advanced hepatocellular carcinoma: final results of Hong Kong-Singapore Hepatocellular Carcinoma Research Collaborative Group study ASCO Meeting Abstracts 31 15-suppl 2013 4117
32. A.F. Buckley, L.J. Burgart, V. Sahai, and S. Kakar Epidermal growth factor receptor expression and gene copy number in conventional hepatocellular carcinoma Am J Clin Pathol 129 2 2008 245 251
33. M.J. Blivet-Van Eggelpoel, H. Chettouh, L. Fartoux, L. Aoudjehane, V. Barbu, and C. Rey Epidermal growth factor receptor and HER-3 restrict cell response to sorafenib in hepatocellular carcinoma cells J Hepatol 57 1 2012 108 115
34. Z. Ezzoukhry, C. Louandre, E. Trecherel, C. Godin, B. Chauffert, and S. Dupont EGFR activation is a potential determinant of primary resistance of hepatocellular carcinoma cells to sorafenib Int J Cancer 131 12 2012 2961 2969
35. M.B. Thomas, J.S. Morris, R. Chadha, M. Iwasaki, H. Kaur, and E. Lin Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma J Clin Oncol 27 6 2009 843 850
36. A.O. Kaseb, E. Garrett-Mayer, J.S. Morris, L. Xiao, E. Lin, and G. Onicescu Efficacy of bevacizumab plus erlotinib for advanced hepatocellular carcinoma and predictors of outcome: final results of a phase II trial Oncology 82 2 2012 67 74
37. P.A. Philip, M.R. Mahoney, K.D. Holen, D.W. Northfelt, H.C. Pitot, and J. Picus Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer Cancer 118 9 2012 2424 2430
38. T. Yau, H. Wong, P. Chan, T.J. Yao, R. Pang, and T.T. Cheung Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease Invest New Drugs 30 6 2012 2384 2390
39. C.H. Hsu, Y.K. Kang, T.S. Yang, C.T. Shun, Y.Y. Shao, and W.C. Su Bevacizumab with erlotinib as first-line therapy in Asian patients with advanced hepatocellular carcinoma: a multicenter phase II study Oncology 85 1 2013 44 52
40. R. Govindarajan, E. Siegel, I. Makhoul, and S. Williamson Bevacizumab and erlotinib in previously untreated inoperable and metastatic hepatocellular carcinoma Am J Clin Oncol 36 3 2013 254 257
41. E.G. Chiorean, R. Ramasubbaiah, M. Yu, J. Picus, J.A. Bufill, and Y. Tong Phase II trial of erlotinib and docetaxel in advanced and refractory hepatocellular and biliary cancers: Hoosier Oncology Group GI06-101 Oncologist 17 1 2012 13
42. A. Asnacios, L. Fartoux, O. Romano, C. Tesmoingt, S.S. Louafi, and T. Mansoubakht Gemcitabine plus oxaliplatin (GEMOX) combined with cetuximab in patients with progressive advanced stage hepatocellular carcinoma: results of a multicenter phase 2 study Cancer 112 12 2008 2733 2739
43. P.J. O'Dwyer, B.J. Giantonio, D.E. Levy, J.S. Kauh, D.B. Fitzgerald, and A.B. Benson Gefitinib in advanced unresectable hepatocellular carcinoma: results from the Eastern Cooperative Oncology Group's Study E1203 ASCO Meeting Abstracts 24 18-suppl 2006 4143
44. A.X. Zhu, K. Stuart, L.S. Blaszkowsky, A. Muzikansky, D.P. Reitberg, and J.W. Clark Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma Cancer 110 3 2007 581 589
45. A.X. Zhu, O. Rosmorduc, J. Evans, P. Ross, A. Santoro, and F.J. Carrilho Search: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with hepatocellular carcinoma (HCC) Ann Oncol 23 9 2012
46. Y. Hoshida, S. Toffanin, A. Lachenmayer, A. Villanueva, B. Minguez, and J.M. Llovet Molecular classification and novel targets in hepatocellular carcinoma: recent advancements Semin Liver Dis 30 1 2010 35 51
47. A.X. Zhu, M. Kudo, E. Assenat, S. Cattan, Y.-K. Kang, and H.Y. Lim EVOLVE-1: phase 3 study of everolimus for advanced HCC that progressed during or after sorafenib ASCO Meeting Abstracts 32 3-suppl 2014 172
48. J.C. Sachdev, A.Y. Javed, A.B. Weir, R.I. Korn, S.M. Gulla, and R.G. Newbold A phase II study of temsirolimus in previously treated advanced hepatocellular carcinoma ASCO Meeting Abstracts 2014 Abstract 4098
49. S.L. Chan, F. Mo, E.P. Hui, J. Koh, C. Chu, and J. Hui A phase I study of temsirolimus as novel therapeutic drug for patients with unresectable hepatocellular carcinoma (HCC) ASCO Meeting Abstracts 31 15-suppl 2013 e15048
50. R.K. Kelley, H.S. Nimeiri, P.N. Munster, M.T. Vergo, Y. Huang, and C.M. Li Temsirolimus combined with sorafenib in hepatocellular carcinoma: a phase I dose-finding trial with pharmacokinetic and biomarker correlates Ann Oncol 24 7 2013 1900 1907
51. J.J. Knox, R. Qin, J.R. Strosberg, A. Kaubisch, A.B. El-Khoueiry, and T.B. Bekaii-Saab A phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in patients with advanced hepatocellular carcinoma (HCC) ASCO Meeting Abstracts 30 15-suppl 2012 4099
52. A.X. Zhu, Y.-K. Kang, O. Rosmorduc, T.R. Evans, A. Santoro, and P.J. Ross Biomarker analyses and association with clinical outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib with or without erlotinib in the phase III SEARCH trial J Clin Oncol 2014 2014 ASCO annual meeting(Abstract 4028)
53. L. Boix, J.L. Rosa, F. Ventura, A. Castells, J. Bruix, and J. Rodes C-met mRNA overexpression in human hepatocellular carcinoma Hepatology 19 1 1994 88 91
54. R. Wang, L.D. Ferrell, S. Faouzi, J.J. Maher, and J.M. Bishop Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice J Cell Biol 153 5 2001 1023 1034
55. B. Xie, R. Xing, P. Chen, Y. Gou, S. Li, and J. Xiao Down-regulation of c-Met expression inhibits human HCC cells growth and invasion by RNA interference J Surg Res 162 2 2010 231 238
56. P. Kaposi-Novak, J.S. Lee, L. Gomez-Quiroz, C. Coulouarn, V.M. Factor, and S.S. Thorgeirsson Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype J Clin Invest 116 6 2006 1582 1595
57. A. Santoro, L. Rimassa, I. Borbath, B. Daniele, S. Salvagni, and J.L. Van Laethem Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study Lancet Oncol 14 1 2013 55 63
58. R. Katayama, A. Aoyama, T. Yamori, J. Qi, T. Oh-hara, and Y. Song Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition Cancer Res 73 10 2013 3087 3096
59. C. Verslype, A.L. Cohn, R.K. Kelley, T.-S. Yang, W.-C. Su, and D.A. Ramies Activity of cabozantinib (XL184) in hepatocellular carcinoma: results from a phase II randomized discontinuation trial (RDT) ASCO Meeting Abstracts 30 15-suppl 2012 4007
60. T.C. Yau, W. Sukeepaisarnjaroen, Y. Chao, C.J. Yen, W. Lausoontornsiri, and P.J. Chen A phase I/II study of foretinib, an oral multikinase inhibitor targeting MET, RON, AXL, TIE-2, and VEGFR in advanced hepatocellular carcinoma (HCC) J Clin Oncol 30 15 2012 4108
61. B.H. O'Neil, J.C. Bendell, M.R. Modiano, J.-P.H. Machiels, M.J. Versola, and J.P. Hodge Phase I/II study of E7050 (golvantinib) in combination with sorafenib in patients (pts) with advanced hepatocellular carcinoma (HCC): phase I results ASCO Meeting Abstracts 31 4-suppl 2013 294
62. J.M. Llovet, C.E. Pena, C.D. Lathia, M. Shan, G. Meinhardt, and J. Bruix Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma Clin Cancer Res 18 8 2012 2290 2300
63. E. Breous, and R. Thimme Potential of immunotherapy for hepatocellular carcinoma J Hepatol 54 4 2011 830 834
64. D.M. Pardoll The blockade of immune checkpoints in cancer immunotherapy Nat Rev Cancer 12 4 2012 252 264
65. F.S. Hodi, S.J. O'Day, D.F. McDermott, R.W. Weber, J.A. Sosman, and J.B. Haanen Improved survival with ipilimumab in patients with metastatic melanoma N Engl J Med 363 8 2010 711 723
66. C. Robert, L. Thomas, I. Bondarenko, S. O'Day, J. Weber, and C. Garbe Ipilimumab plus dacarbazine for previously untreated metastatic melanoma N Engl J Med 364 26 2011 2517 2526
67. V. Hernandez-Gea, S. Toffanin, S.L. Friedman, and J.M. Llovet Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma Gastroenterology 144 3 2013 512 527
68. S. Champiat, C. Ferte, S. Lebel-Binay, A. Eggermont, and J.C. Soria Exomics and immunogenics: bridging mutational load and immune checkpoints efficacy Oncoimmunology 3 1 2014 e27817
69. J.C. Nault, and J. Zucman-Rossi Genetics of hepatocellular carcinoma: the next generation J Hepatol 60 1 2014 224 226
70. B. Sangro, C. Gomez-Martin, M. de la Mata, M. Iñarrairaegui, E. Garralda, and P. Barrera A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C J Hepatol 59 1 2013 81 88
71. S.L. Topalian, F.S. Hodi, J.R. Brahmer, S.N. Gettinger, D.C. Smith, and D.F. McDermott Safety, activity, and immune correlates of anti-PD-1 antibody in cancer N Engl J Med 366 26 2012 2443 2454
72. O. Hamid, C. Robert, A. Daud, F.S. Hodi, W.J. Hwu, and R. Kefford Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma N Engl J Med 369 2 2013 134 144
73. J.R. Brahmer, S.S. Tykodi, L.Q. Chow, W.J. Hwu, S.L. Topalian, and P. Hwu Safety and activity of anti-PD-L1 antibody in patients with advanced cancer N Engl J Med 366 26 2012 2455 2465
74. B.J. Wang, J.J. Bao, J.Z. Wang, Y. Wang, M. Jiang, and M.Y. Xing Immunostaining of PD-1/PD-Ls in liver tissues of patients with hepatitis and hepatocellular carcinoma World J Gastroenterol 17 28 2011 3322 3329
75. Z. Zeng, F. Shi, L. Zhou, M.N. Zhang, Y. Chen, and X.J. Chang Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma PLoS One 6 9 2011 e23621
76. D.M. Kuang, Q. Zhao, C. Peng, J. Xu, J.P. Zhang, and C. Wu Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1 J Exp Med 206 6 2009 1327 1337
77. B. Sangro, T.S. Crocenzi, T.H. Welling, M. Inarrairaegui, J. Prieto, and C. Fuertes Phase I dose escalation study of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in patients (pts) with advanced hepatocellular carcinoma (HCC) with or without chronic viral hepatitis ASCO Meeting Abstracts 31 15-suppl 2013 TPS3111
78. N.H. Segal, O. Hamid, W.J. Hwu, C. Massard, M. Butler, and S. Antonia A phase I multi-arm dose-expansion study of the anti-programmed cell death-ligand-1 (PD-L1) antibody MEDI4736: preliminary data ESMO Congress 2014 2014 Abstract 5888(Poster 1058PD)
79. J. Heo, T. Reid, L. Ruo, C.J. Breitbach, S. Rose, and M. Bloomston Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer Nat Med 19 3 2013 329 336
80. A. Segler, and A.M. Tsimberidou Lenalidomide in solid tumors Cancer Chemother Pharmacol 69 6 2012 1393 1406
81. B.H. O'Neil, L.W. Goff, J.S. Kauh, J.R. Strosberg, T.S. Bekaii-Saab, and R.M. Lee Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma J Clin Oncol 29 17 2011 2350 2356
82. S.P. Choo, Q.S. Ng, W.J.J. Chen, C.K. Tham, W.-P. Yong, and L.Z. Wang A phase I/II study of AZD6244 in combination with sorafenib in advanced hepatocellular carcinoma ASCO Meeting Abstracts 30 15-suppl 2012 4100
83. H.Y. Lim, C.-J. Yen, W.-Y. Tak, J. Heo, H.J. Choi, and C.-Y. Lin A phase II trial of MEK inhibitor BAY 86-9766 in combination with sorafenib as first-line systemic treatment for patients with unresectable hepatocellular carcinoma (HCC) ASCO Meeting Abstracts 30 15-suppl 2012 4103
84. M. Ruden, and N. Puri Novel anticancer therapeutics targeting telomerase Cancer Treat Rev 39 5 2013 444 456
85. J.C. Nault, J. Calderaro, L.D. Tommaso, C. Balabaud, E.S. Zafrani, and P. Bioulac-Sage TERT promoter mutation is an early somatic genetic alteration in the transformation of premalignant nodules in hepatocellular carcinoma on cirrhosis Hepatology 60 6 2014 1983 1992
86. N. Turner, and R. Grose Fibroblast growth factor signalling: from development to cancer Nat Rev Cancer 10 2 2010 116 129
87. E.T. Sawey, M. Chanrion, C. Cai, G. Wu, J. Zhang, and L. Zender Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening Cancer Cell 19 3 2011 347 358
88. S.-M. Ahn, S.J. Jang, J.H. Shim, D. Kim, S.-M. Hong, and C.O. Sung Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification Hepatology 60 6 2014 1972 1982
89. R. Dienstmann, F. Andre, J. Soria, J. Tabernero, F.G.M. De Braud, and R. Cereda Significant antitumor activity of E-3810, a novel Fgfr and Vegfr inhibitor, in patients with Fgfr1 amplified breast cancer Ann Oncol 23 2012 116 117
90. G.K. Abou-Alfa, M. Capanu, E.M. O'Reilly, J. Ma, J.F. Chou, and B. Gansukh A phase II study of cixutumumab (IMC-A12, NSC742460) in advanced hepatocellular carcinoma J Hepatol 60 2 2014 319 324
91. S.J. Faivre, L. Fartoux, M. Bouattour, F. Bumsel, C. Dreyer, and E. Raymond A phase I study of AVE1642, a human monoclonal antibody-blocking insulin-like growth factor-1 receptor (IGF-1R), given as a single agent and in combination with sorafenib as first-line therapy in patients with advanced hepatocellular carcinoma (HCC) ASCO Meeting Abstracts 29 4-suppl 2011 270
92. T.E. Ciuleanu, I. Bazin, D. Lungulescu, L. Miron, I. Bondarenko, and A. Deptala Final analysis: randomized, blinded, placebo-controlled phase II trial of sorafenib with and without mapatumumab in patients with advanced hepatocellular carcinoma ASCO Meeting Abstracts 2014 Abstract 4029
93. L. Libbrecht, T. Severi, D. Cassiman, S. VanderBorght, J. Pirenne, and F. Nevens Glypican-3 expression distinguishes small hepatocellular carcinomas from cirrhosis, dysplastic nodules, and focal nodular hyperplasia-like nodules Am J Surg Pathol 30 11 2006 1405 1411
94. M. Capurro, I.R. Wanless, M. Sherman, G. Deboer, W. Shi, and E. Miyoshi Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma Gastroenterology 125 1 2003 89 97
95. A.X. Zhu, P.J. Gold, A.B. El-Khoueiry, T.A. Abrams, H. Morikawa, and N. Ohishi First-in-man phase I study of GC33, a novel recombinant humanized antibody against glypican-3, in patients with advanced hepatocellular carcinoma Clin Cancer Res 19 4 2013 920 928
96. C.J. Yen, B. Daniele, M. Kudo, P. Merle, J.W. Park, and P. Ross Randomized phase II trial of intravenous RO5137382/GC33 at 1600 mg every other week and placebo in previously treated patients with unresectable advanced hepatocellular carcinoma J Clin Oncol 2014 2014 ASCO Annual Meeting(Abstract 4102)
97. G. Abou-Alfa, C.J. Yen, J.A. Carrasquillo, C. Hsu, B. Gansukh, and J. Ma Phase Ib study of RO2137382/GC33 in combination with sorafenib in patients with advanced hepatocellular carcinoma J Clin Oncol 2014 Abstract 4100
98. J.P. Iredale Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ J Clin Invest 117 3 2007 539 548
99. S.J. Faivre, A. Santoro, R.K. Kelley, P. Merle, E. Gane, and J.-Y. Douillard A phase 2 study of a novel transforming growth factor-beta (TGF-{beta}1) receptor I kinase inhibitor, LY2157299 monohydrate (LY), in patients with advanced hepatocellular carcinoma (HCC) ASCO Meeting Abstracts 32 3-suppl 2014 LBA173
100. B.J. Dillon, V.G. Prieto, S.A. Curley, C.M. Ensor, F.W. Holtsberg, and J.S. Bomalaski Incidence and distribution of argininosuccinate synthetase deficiency in human cancers: a method for identifying cancers sensitive to arginine deprivation Cancer 100 4 2004 826 833
101. P.N. Cheng, T.L. Lam, W.M. Lam, S.M. Tsui, A.W. Cheng, and W.H. Lo Pegylated recombinant human arginase (rhArg-peg5,000mw) inhibits the in vitro and in vivo proliferation of human hepatocellular carcinoma through arginine depletion Cancer Res 67 1 2007 309 317
102. T.S. Yang, S.N. Lu, Y. Chao, I.S. Sheen, C.C. Lin, and T.E. Wang A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients Br J Cancer 103 7 2010 954 960
103. E.S. Glazer, M. Piccirillo, V. Albino, R. Di Giacomo, R. Palaia, and A.A. Mastro Phase II study of pegylated arginine deiminase for non-resectable and metastatic hepatocellular carcinoma J Clin Oncol 28 13 2010 2220 2226
104. T. Yau, P.N. Cheng, P. Chan, W. Chan, L. Chen, and J. Yuen A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma Invest New Drugs 31 1 2013 99 107
105. T.C. Yau, P.N. Cheng, P. Chan, R. Pang, and R.T. Poon Preliminary efficacy, safety, pharmacokinetics, and quality of life study of pegylated recombinant human arginase 1 in patients with advanced hepatocellular carcinoma J Clin Oncol 2014 Abstract e15137
106. F. Izzo, P. Marra, G. Beneduce, G. Castello, P. Vallone, and V. De Rosa Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies J Clin Oncol 22 10 2004 1815 1822
107. W. Yeo, H.C. Chung, S.L. Chan, L.Z. Wang, R. Lim, and J. Picus Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase I/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group J Clin Oncol 30 27 2012 3361 3367
108. M. Bitzer, M. Horger, T.M. Ganten, U.M. Lauer, M.A. Woerns, and J.T. Siveke Efficacy, safety, tolerability, and PK of the HDAC inhibitor resminostat in sorafenib-refractory hepatocellular carcinoma (HCC): phase II SHELTER study ASCO Meeting Abstracts 30 15-suppl 2012 4115
109. J.M. Llovet, and V. Hernandez-Gea Hepatocellular carcinoma: reasons for phase III failure and novel perspectives on trial design Clin Cancer Res 20 8 2014 2072 2079
110. L. Ding, T.J. Ley, D.E. Larson, C.A. Miller, D.C. Koboldt, and J.S. Welch Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing Nature 481 7382 2012 506 510
111. E.D. Pleasance, R.K. Cheetham, P.J. Stephens, D.J. McBride, S.J. Humphray, and C.D. Greenman A comprehensive catalogue of somatic mutations from a human cancer genome Nature 463 7278 2010 191 196
112. D.W. Parsons, S. Jones, X. Zhang, J.C. Lin, R.J. Leary, and P. Angenendt An integrated genomic analysis of human glioblastoma multiforme Science 321 5897 2008 1807 1812
113. M.F. Berger, M.S. Lawrence, F. Demichelis, Y. Drier, K. Cibulskis, and A.Y. Sivachenko The genomic complexity of primary human prostate cancer Nature 470 7333 2011 214 220
114. T.J. Ley, E.R. Mardis, L. Ding, B. Fulton, M.D. McLellan, and K. Chen DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome Nature 456 7218 2008 66 72
115. S.P. Cleary, W.R. Jeck, X. Zhao, K. Chen, S.R. Selitsky, and G.L. Savich Identification of driver genes in hepatocellular carcinoma by exome sequencing Hepatology 58 5 2013 1693 1702
116. Z. Kan, H. Zheng, X. Liu, S. Li, T.D. Barber, and Z. Gong Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma Genome Res 23 9 2013 1422 1433
117. C. Guichard, G. Amaddeo, S. Imbeaud, Y. Ladeiro, L. Pelletier, and I.B. Maad Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma Nat Genet 44 6 2012 694 698
118. COSMIC, < http://cancer.sanger.ac.uk/cancergenome/projects/cosmic/ >.
119. P.B. Chapman, A. Hauschild, C. Robert, J.B. Haanen, P. Ascierto, and J. Larkin Improved survival with vemurafenib in melanoma with BRAF V600E mutation N Engl J Med 364 26 2011 2507 2516
120. A.T. Shaw, D.W. Kim, K. Nakagawa, T. Seto, L. Crino, and M.J. Ahn Crizotinib versus chemotherapy in advanced ALK-positive lung cancer N Engl J Med 368 25 2013 2385 2394
121. P.C. Fong, D.S. Boss, T.A. Yap, A. Tutt, P. Wu, and M. Mergui-Roelvink Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers N Engl J Med 361 2 2009 123 134
122. S. Sleijfer, J. Bogaerts, and L.L. Siu Designing transformative clinical trials in the cancer genome era J Clin Oncol 31 15 2013 1834 1841
123. J. Verweij, M. de Jonge, F. Eskens, and S. Sleijfer Moving molecular targeted drug therapy towards personalized medicine: issues related to clinical trial design Mol Oncol 6 2 2012 196 203
124. A. Hollebecque, C. Massard, and J.C. Soria Implementing precision medicine initiatives in the clinic: a new paradigm in drug development Curr Opin Oncol 26 3 2014 340 346
125. D.Y. Chiang, A. Villanueva, Y. Hoshida, J. Peix, P. Newell, and B. Minguez Focal gains of VEGFA and molecular classification of hepatocellular carcinoma Cancer Res 68 16 2008 6779 6788
126. A.M. Tsimberidou, A.M. Eggermont, and R.L. Schilsky Precision cancer medicine: the future is now, only better Am Soc Clin Oncol Educ Book 2014 61 69
127. B. Tran, J.E. Dancey, S. Kamel-Reid, J.D. McPherson, P.L. Bedard, and A.M. Brown Cancer genomics: technology, discovery, and translation J Clin Oncol 30 6 2012 647 660
128. I.O. Ng, X.Y. Guan, R.T. Poon, S.T. Fan, and J.M. Lee Determination of the molecular relationship between multiple tumour nodules in hepatocellular carcinoma differentiates multicentric origin from intrahepatic metastasis J Pathol 199 3 2003 345 353
129. J.A. Engelman, K. Zejnullahu, T. Mitsudomi, Y. Song, C. Hyland, and J.O. Park MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling Science 316 5827 2007 1039 1043
130. C.M. Johannessen, J.S. Boehm, S.Y. Kim, S.R. Thomas, L. Wardwell, and L.A. Johnson COT drives resistance to RAF inhibition through MAP kinase pathway reactivation Nature 468 7326 2010 968 972
131. C. Holohan, S. Van Schaeybroeck, D.B. Longley, and P.G. Johnston Cancer drug resistance: an evolving paradigm Nat Rev Cancer 13 10 2013 714 726
132. L.V. Sequist, B.A. Waltman, D. Dias-Santagata, S. Digumarthy, A.B. Turke, and P. Fidias Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors Sci Transl Med 3 75 2011 75ra26
133. Y.L. Choi, M. Soda, Y. Yamashita, T. Ueno, J. Takashima, and T. Nakajima EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors N Engl J Med 363 18 2010 1734 1739
134. S.J. Dawson, D.W. Tsui, M. Murtaza, H. Biggs, O.M. Rueda, and S.F. Chin Analysis of circulating tumor DNA to monitor metastatic breast cancer N Engl J Med 368 13 2013 1199 1209
135. M.J. Higgins, D. Jelovac, E. Barnathan, B. Blair, S. Slater, and P. Powers Detection of tumor PIK3CA status in metastatic breast cancer using peripheral blood Clin Cancer Res 18 12 2012 3462 3469
136. M. Murtaza, S.J. Dawson, D.W. Tsui, D. Gale, T. Forshew, and A.M. Piskorz Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA Nature 497 7447 2013 108 112
137. S. Maheswaran, L.V. Sequist, S. Nagrath, L. Ulkus, B. Brannigan, and C.V. Collura Detection of mutations in EGFR in circulating lung-cancer cells N Engl J Med 359 4 2008 366 377