The emerging role of MET/HGF inhibitors in oncology

Cancer Treatment Reviews

Volumn 39, Issue 7, 2013, Pages 793-801

  Scagliotti, Giorgio V ^a   Novello, Silvia ^a   von Pawel, Joachim ^b  

^a UNIVERSITY OF TURIN   (Italy)

^b Asklepios Clinic Munich Gauting   (Germany)

Author keywords

ARQ 197; HGF receptor; MET protooncogene; Receptor tyrosine kinase; Tivantinib; Tyrosine kinase inhibitor

Indexed keywords

5 (2,6 DICHLOROBENZYLSULFONYL) 3 [3,5 DIMETHYL 4 [2 (1 PYRROLIDINYLMETHYL) 1 PYRROLIDINYLCARBONYL] 1H PYRROL 2 YLMETHYLENE] 1,3 DIHYDRO 2H INDOL 2 ONE; ABIRATERONE; AMG 208; AMUVATINIB; BMS 777607; CABOZANTINIB; CAPECITABINE; CISPLATIN; CRIZOTINIB; DOCETAXEL; ENZALUTAMIDE; EPIRUBICIN; ERLOTINIB; FICLATUZUMAB; FORETINIB; GOLVATINIB; METHYLNITRONITROSOGUANIDINE; MK 2461; MK 8033; ONARTUZUMAB; PLACEBO; PREDNISONE; RILOTUMUMAB; SCATTER FACTOR; TIVANTINIB; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANTINEOPLASTIC ACTIVITY; BREAST CANCER; BREAST METASTASIS; CANCER CHEMOTHERAPY; CANCER SURVIVAL; CARCINOMA; CASTRATION RESISTANT PROSTATE CANCER; COLON CANCER; COLORECTAL CANCER; DRUG SAFETY; FAMILIAL CANCER; GENE AMPLIFICATION; GENE OVEREXPRESSION; GLIOBLASTOMA; HUMAN; INFORMATION RETRIEVAL; KIDNEY CARCINOMA; LIVER CANCER; LIVER CELL; LIVER CELL CARCINOMA; LUNG ADENOCARCINOMA; LUNG CANCER; LUNG NON SMALL CELL CANCER; MELANOMA; MICROARRAY ANALYSIS; MISSENSE MUTATION; MONOTHERAPY; ONCOGENE; OSTEOSARCOMA; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL (TOPIC); POINT MUTATION; PROGRESSION FREE SURVIVAL; REVIEW; SARCOMA; STOMACH ADENOCARCINOMA; STOMACH CANCER; THYROID MEDULLARY CARCINOMA; TUMOR REGRESSION;

ARQ 197; HGF RECEPTOR; MET PROTOONCOGENE; RECEPTOR TYROSINE KINASE; TIVANTINIB; TYROSINE KINASE INHIBITOR;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; DRUG RESISTANCE, NEOPLASM; HEPATOCYTE GROWTH FACTOR; HUMANS; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-MET;

EID: 84881542709     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2013.02.001     Document Type: Review

References (124)

1. Birchmeier C., Birchmeier W., Gherardi E., Vande Woude G.F. Met, metastasis, motility and more. Nat Rev Mol Cell Biol 2003, 4:915-925.
2. Comoglio P.M., Giordano S., Trusolino L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 2008, 7:504-516.
3. Gherardi E., Birchmeier W., Birchmeier C., Woude G.V. Targeting MET in cancer: rationale and progress. Nat Rev Cancer 2012, 12:89-103.
4. Trusolino L., Bertotti A., Comoglio P.M. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol 2010, 11:834-848.
5. Andermarcher E., Surani M.A., Gherardi E. Co-expression of the HGF/SF and c-met genes during early mouse embryogenesis precedes reciprocal expression in adjacent tissues during organogenesis. Dev Genet 1996, 18:254-266.
6. Bladt F., Riethmacher D., Isenmann S., Aguzzi A., Birchmeier C. Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud. Nature 1995, 376:768-771.
7. Bussolino F., Di Renzo M.F., Ziche M., et al. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell Biol 1992, 119:629-641.
8. Streit A., Stern C.D., Thery C., et al. A role for HGF/SF in neural induction and its expression in Hensen's node during gastrulation. Development 1995, 121:813-824.
9. Takayama H., La Rochelle W.J., Anver M., Bockman D.E., Merlino G. Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development. Proc Natl Acad Sci U S A 1996, 93:5866-5871.
10. Matsumoto K., Nakamura T. Hepatocyte growth factor: renotropic role and potential therapeutics for renal diseases. Kidney Int 2001, 59:2023-2038.
11. Michalopoulos G.K., DeFrances M.C. Liver regeneration. Science 1997, 276:60-66.
12. Nakamura T., Mizuno S., Matsumoto K., Sawa Y., Matsuda H. Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF. J Clin Invest 2000, 106:1511-1519.
13. Schmidt C., Bladt F., Goedecke S., et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 1995, 373:699-702.
14. Liu Y., Yang J. Hepatocyte growth factor: new arsenal in the fights against renal fibrosis?. Kidney Int 2006, 70:238-240.
15. Ueki T., Kaneda Y., Tsutsui H., et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat Med 1999, 5:226-230.
16. Watanabe M., Ebina M., Orson F.M., et al. Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis. Mol Ther 2005, 12:58-67.
17. Weidner K.M., Di Cesare S., Sachs M., Brinkmann V., Behrens J., Birchmeier W. Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Nature 1996, 384:173-176.
18. Zeng Q., Chen S., You Z., et al. Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa B. J Biol Chem 2002, 277:25203-25208.
19. Appleman L.J. MET signaling pathway: a rational target for cancer therapy. J Clin Oncol 2011, 29:4837-4838.
20. Feng Y., Thiagarajan P.S., Ma P.C. MET signaling: novel targeted inhibition and its clinical development in lung cancer. J Thorac Oncol 2012, 7:459-467.
21. Van Andel Institute. Hepatocyte growth factor/scatter factor (HGF/SF), MET and cancer references; 2012. Accessed November 5, 2012. http://www.vai.org/met/.
22. Cipriani N.A., Abidoye O.O., Vokes E., Salgia R. MET as a target for treatment of chest tumors. Lung Cancer 2009, 63:169-179.
23. Xiao G.H., Jeffers M., Bellacosa A., Mitsuuchi Y., Vande Woude G.F., Testa J.R. Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Proc Natl Acad Sci U S A 2001, 98:247-252.
24. Cooper C.S., Park M., Blair D.G., et al. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 1984, 311:29-33.
25. Liang T.J., Reid A.E., Xavier R., Cardiff R.D., Wang T.C. Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. J Clin Invest 1996, 97:2872-2877.
26. Boccaccio C., Sabatino G., Medico E., et al. The MET oncogene drives a genetic programme linking cancer to haemostasis. Nature 2005, 434:396-400.
27. Soman N.R., Correa P., Ruiz B.A., Wogan G.N. The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. Proc Natl Acad Sci U S A 1991, 88:4892-4896.
28. Sattler M., Reddy M.M., Hasina R., Gangadhar T., Salgia R. The role of the c-Met pathway in lung cancer and the potential for targeted therapy. Ther Adv Med Oncol 2011, 3:171-184.
29. Wang R., Ferrell L.D., Faouzi S., Maher J.J., Bishop J.M. Activation of the Met receptor by cell attachment induces and sustains hepatocellular carcinomas in transgenic mice. J Cell Biol 2001, 153:1023-1034.
30. Di Renzo M.F., Olivero M., Giacomini A., et al. Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer. Clin Cancer Res 1995, 1:147-154.
31. Lee J.H., Han S.U., Cho H., et al. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 2000, 19:4947-4953.
32. Park W.S., Dong S.M., Kim S.Y., et al. Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res 1999, 59:307-310.
33. Schmidt L., Duh F.M., Chen F., et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 1997, 16:68-73.
34. Graziano F., Galluccio N., Lorenzini P., et al. Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. J Clin Oncol 2011, 29:4789-4795.
35. Choueiri T.K., Vaishampayan U., Rosenberg J.E., et al. Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma. J Clin Oncol 2013, 31:181-186.
36. Di Renzo M.F., Olivero M., Martone T., et al. Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene 2000, 19:1547-1555.
37. Jagadeeswaran R., Ma P.C., Seiwert T.Y., et al. Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma. Cancer Res 2006, 66:352-361.
38. Ma P.C., Jagadeeswaran R., Jagadeesh S., et al. Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer. Cancer Res 2005, 65:1479-1488.
39. Ma P.C., Kijima T., Maulik G., et al. C-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res 2003, 63:6272-6281.
40. Puri N., Ahmed S., Janamanchi V., et al. C-Met is a potentially new therapeutic target for treatment of human melanoma. Clin Cancer Res 2007, 13:2246-2253.
41. Graveel C., Su Y., Koeman J., et al. Activating Met mutations produce unique tumor profiles in mice with selective duplication of the mutant allele. Proc Natl Acad Sci U S A 2004, 101:17198-17203.
42. Peschard P., Fournier T.M., Lamorte L., et al. Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein. Mol Cell 2001, 8:995-1004.
43. Ferracini R., Di Renzo M.F., Scotlandi K., et al. The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. Oncogene 1995, 10:739-749.
44. Ferracini R., Olivero M., Di Renzo M.F., et al. Retrogenic expression of the MET proto-oncogene correlates with the invasive phenotype of human rhabdomyosarcomas. Oncogene 1996, 12:1697-1705.
45. Koochekpour S., Jeffers M., Rulong S., et al. Met and hepatocyte growth factor/scatter factor expression in human gliomas. Cancer Res 1997, 57:5391-5398.
46. Tuck A.B., Park M., Sterns E.E., Boag A., Elliott B.E. Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma. Am J Pathol 1996, 148:225-232.
47. Bellusci S., Moens G., Gaudino G., et al. Creation of an hepatocyte growth factor/scatter factor autocrine loop in carcinoma cells induces invasive properties associated with increased tumorigenicity. Oncogene 1994, 9:1091-1099.
48. Jeffers M., Rong S., Anver M., Vande Woude G.F. Autocrine hepatocyte growth factor/scatter factor-Met signaling induces transformation and the invasive/metastatic phenotype in C127 cells. Oncogene 1996, 13:853-856.
49. Otsuka T., Takayama H., Sharp R., et al. C-Met autocrine activation induces development of malignant melanoma and acquisition of the metastatic phenotype. Cancer Res 1998, 58:5157-5167.
50. Rong S., Segal S., Anver M., Resau J.H., Vande Woude G.F. Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proc Natl Acad Sci U S A 1994, 91:4731-4735.
51. Takayama H., LaRochelle W.J., Sharp R., et al. Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. Proc Natl Acad Sci U S A 1997, 94:701-706.
52. Corso S., Comoglio P.M., Giordano S. Cancer therapy: can the challenge be MET?. Trends Mol Med 2005, 11:284-292.
53. Bauer T.W., Somcio R.J., Fan F., et al. Regulatory role of c-Met in insulin-like growth factor-I receptor-mediated migration and invasion of human pancreatic carcinoma cells. Mol Cancer Ther 2006, 5:1676-1682.
54. Khoury H., Naujokas M.A., Zuo D., et al. HGF converts ErbB2/Neu epithelial morphogenesis to cell invasion. Mol Biol Cell 2005, 16:550-561.
55. Yamamoto N., Mammadova G., Song R.X., Fukami Y., Sato K. Tyrosine phosphorylation of p145met mediated by EGFR and Src is required for serum-independent survival of human bladder carcinoma cells. J Cell Sci 2006, 119:4623-4633.
56. Engelman J.A., Zejnullahu K., Mitsudomi T., et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007, 316:1039-1043.
57. Abounader R., Laterra J. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol 2005, 7:436-451.
58. Grant D.S., Kleinman H.K., Goldberg I.D., et al. Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci U S A 1993, 90:1937-1941.
59. Zhang Y.W., Su Y., Volpert O.V., Vande Woude G.F. Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation. Proc Natl Acad Sci U S A 2003, 100:12718-12723.
60. Pennacchietti S., Michieli P., Galluzzo M., Mazzone M., Giordano S., Comoglio P.M. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 2003, 3:347-361.
61. Exelixis Inc. Dual inhibition of MET and VEGF signaling with cabozantinib blocks tumor invasiveness and metastasis. Press release, February 24, 2012. Accessed November 5, 2012. http://ir.exelixis.com/phoenix.zhtml?c=120923&p=irol-newsArticle_print&ID=1665087&highlight=
62. Gallego M.I., Bierie B., Hennighausen L. Targeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways. Oncogene 2003, 22:8498-8508.
63. Jeffers M., Fiscella M., Webb C.P., Anver M., Koochekpour S., Vande Woude G.F. The mutationally activated Met receptor mediates motility and metastasis. Proc Natl Acad Sci U S A 1998, 95:14417-14422.
64. Ridley A.J., Comoglio P.M., Hall A. Regulation of scatter factor/hepatocyte growth factor responses by Ras, Rac, and Rho in MDCK cells. Mol Cell Biol 1995, 15:1110-1122.
65. Vermeulen L., De Sousa E.M.F., van der Heijden M., et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 2010, 12:468-476.
66. Birchmeier C., Gherardi E. Developmental roles of HGF/SF and its receptor, the c-Met tyrosine kinase. Trends Cell Biol 1998, 8:404-410.
67. De Bacco F., Luraghi P., Medico E., et al. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J Natl Cancer Inst 2011, 103:645-661.
68. Corso S., Ghiso E., Cepero V., et al. Activation of HER family members in gastric carcinoma cells mediates resistance to MET inhibition. Mol Cancer 2010, 9:121.
69. McDermott U., Pusapati R.V., Christensen J.G., Gray N.S., Settleman J. Acquired resistance of non-small cell lung cancer cells to MET kinase inhibition is mediated by a switch to epidermal growth factor receptor dependency. Cancer Res 2010, 70:1625-1634.
70. Cepero V., Sierra J.R., Corso S., et al. MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors. Cancer Res 2010, 70:7580-7590.
71. Qi J., McTigue M.A., Rogers A., et al. Multiple mutations and bypass mechanisms can contribute to development of acquired resistance to MET inhibitors. Cancer Res 2011, 71:1081-1091.
72. Ma P.C., Tretiakova M.S., MacKinnon A.C., et al. Expression and mutational analysis of MET in human solid cancers. Genes Chromosomes Cancer 2008, 47:1025-1037.
73. Rikova K., Guo A., Zeng Q., et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007, 131:1190-1203.
74. Beau-Faller M., Ruppert A.M., Voegeli A.C., et al. MET gene copy number in non-small cell lung cancer: molecular analysis in a targeted tyrosine kinase inhibitor naive cohort. J Thorac Oncol 2008, 3:331-339.
75. Cappuzzo F., Marchetti A., Skokan M., et al. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol 2009, 27:1667-1674.
76. Go H., Jeon Y.K., Park H.J., Sung S.W., Seo J.W., Chung D.H. High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer. J Thorac Oncol 2010, 5:305-313.
77. Kanteti R., Yala S., Ferguson M.K., Salgia R. MET, HGF, EGFR, and PXN gene copy number in lung cancer using DNA extracts from FFPE archival samples and prognostic significance. J Environ Pathol Toxicol Oncol 2009, 28:89-98.
78. Onitsuka T., Uramoto H., Ono K., et al. Comprehensive molecular analyses of lung adenocarcinoma with regard to the epidermal growth factor receptor, K-ras, MET, and hepatocyte growth factor status. J Thorac Oncol 2010, 5:591-596.
79. Dziadziuszko R., Wynes M.W., Singh S., et al. Correlation between MET gene copy number by silver in situ hybridization and protein expression by immunohistochemistry in non-small cell lung cancer. J Thorac Oncol 2012, 7:340-347.
80. Ichimura E., Maeshima A., Nakajima T., Nakamura T. Expression of c-met/HGF receptor in human non-small cell lung carcinomas in vitro and in vivo and its prognostic significance. Jpn J Cancer Res 1996, 87:1063-1069.
81. Rodig S, Sequist LV, von Pawel J, et al. An exploratory biomarker analysis evaluating the effect of the c-MET inhibitor tivantinib (ARQ 197) and erlotinib in NSCLC patients in a randomized, double-blinded phase 2 study. Presented at: Annual Meeting of the American Association for Cancer Research; March 31-April 4, 2012; Chicago (IL). Abstract 1729.
82. Spigel D.R., Ervin T.J., Ramlau R., et al. Final efficacy results from OAM4558g, a randomized phase II study evaluating MetMAb or placebo in combination with erlotinib in advanced NSCLC [oral]. J Clin Oncol 2011, 29(Suppl.). Abstract 7505.
83. Tsao M.S., Liu N., Chen J.R., et al. Differential expression of Met/hepatocyte growth factor receptor in subtypes of non-small cell lung cancers. Lung Cancer 1998, 20:1-16.
84. Tsuta K., Kozu Y., Mimae T., et al. C-MET/Phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas. J Thorac Oncol 2012, 7:331-339.
85. Bean J., Brennan C., Shih J.Y., et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci U S A 2007, 104:20932-20937.
86. Turke A.B., Zejnullahu K., Wu Y.L., et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 2010, 17:77-88.
87. Eathiraj S., Palma R., Volckova E., et al. Discovery of a novel mode of protein kinase inhibition characterized by the mechanism of inhibition of human mesenchymal-epithelial transition factor (c-Met) protein autophosphorylation by ARQ 197. J Biol Chem 2011, 286:20666-20676.
88. Munshi N., Jeay S., Li Y., et al. ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity. Mol Cancer Ther 2010, 9:1544-1553.
89. Santoro A., Simonelli M., Rodriguez-Lope C., et al. A phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis. Br J Cancer 2013, 108:21-24.
90. Goldman J.W., Laux I., Chai F., et al. Phase 1 dose-escalation trial evaluating the combination of the selective MET inhibitor tivantinib (ARQ 197) plus erlotinib. Cancer 2012, 118:5903-5911.
91. Rosen L.S., Senzer N.N., Ganapathi R., et al. A phase I dose-escalation study of tivantinib (ARQ 197) in adult patients with metastatic solid tumors. Clin Cancer Res 2011, 17:7754-7764.
92. Yap T.A., Olmos D., Brunetto A.T., et al. Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies. J Clin Oncol 2011, 29:1271-1279.
93. Sequist L.V., von Pawel J., Garmey E.G., et al. Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer. J Clin Oncol 2011, 29:3307-3315.
94. Previdi S., Abbadessa G., Dalo F., France D.S., Broggini M. Breast cancer-derived bone metastasis can be effectively reduced through specific c-MET inhibitor tivantinib (ARQ 197) and shRNA c-MET knockdown. Mol Cancer Ther 2012, 11:214-223.
95. Daiichi Sankyo Inc; ArQule. ARQ 197 plus erlotinib versus placebo plus erlotinib for the treatment of non-squamous, non-small-cell lung cancer; 2012. Accessed November 5, 2012. http://clinicaltrials.gov/ct2/show/NCT01244191.
96. Scagliotti G.V., Novello S., Schiller J.H., et al. Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer. Clin Lung Cancer 2012, 13:391-395.
97. Kyowa Hakko Kirin Company. A phase 3, randomized, double-blinded, placebo-controlled study of ARQ 197 plus erlotinib versus placebo plus erlotinib in previously treated subjects with locally advanced or metastatic, non-squamous, non-small-cell lung cancer with wild-type epidermal growth factor receptor; 2011. Accessed November 5, 2012. http://clinicaltrials.gov/ct2/show/NCT01377376.
98. Santoro A., Rimassa L., Borbath I., et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomized, placebo-controlled phase 2 study. Lancet Oncol 2013, 14:55-63.
99. Schoffski P., Elisei R., Mueller S., et al. An international, double-blind, randomized, placebo-controlled phase III trial (EXAM) of cabozantinib (XL184) in medullary thyroid carcinoma (MTC) patients (pts) with documented RECIST progression at baseline. J Clin Oncol 2012, 30(Suppl.). Abstract 5508.
100. Exelixis Inc. FDA approves COMETRIQ™ (Cabozantinib) for treatment of progressive, metastatic medullary thyroid cancer. Press release, 2012. Accessed January 24, 2013. http://www.exelixis.com/investors-media/press-releases?cpurl=http%3A%2F%2Fir.exelixis.com/phoenix.zhtml?c=120923%26p=irol-newsArticle%26ID=1763107%26highlight=
101. Gordon M.S., Vogelzang N.J., Schoffski P., et al. Activity of cabozantinib (XL184) in soft tissue and bone: results of a phase II randomized discontinuation trial (RDT) in patients (pts) with advanced solid tumors. J Clin Oncol 2011, 29(Suppl.). Abstract 3010.
102. Gordon M.S., Kluger H.M., Shapiro G., et al. Activity of cabozantinib (XL184) in metastatic melanoma: results from a phase II randomized discontinuation trial (RDT). J Clin Oncol 2012, 30(Suppl.). Abstract 8531.
103. Hellerstedt B.A., Edelman G., Vogelzang N.J., et al. Activity of cabozantinib (XL184) in metastatic NSCLC: Results from a phase II randomized discontinuation trial (RDT). J Clin Oncol 2012, 30(Suppl.). Abstract 7514.
104. Verslype C., Cohn A.L., Kelley R.K., et al. Activity of cabozantinib (XL184) in hepatocellular carcinoma: results from a phase II randomized discontinuation trial (RDT). J Clin Oncol 2012, 30(Suppl.). Abstract 4007.
105. Winer E.P., Tolaney S., Nechushtan H., et al. Activity of cabozantinib (XL184) in metastatic breast cancer (MBC): results from a phase II randomized discontinuation trial (RDT). J Clin Oncol 2012, 30(Suppl.). Abstract 535.
106. Smith D.C., Smith M.R., Sweeney C., et al. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol 2012, Epub ahead of print. 10.1200/JCO.2012.45.0494.
107. Exelixis Inc. Study of cabozantinib (XL184) versus prednisone in men with metastatic castration-resistant prostate cancer previously treated with docetaxel and abiraterone or MDV3100 (COMET-1); 2013. Accessed January 10, 2013. http://clinicaltrials.gov/ct2/show/NCT01605227.
108. Wakelee H.A., Gettinger S.N., Engelman J.A., et al. A phase Ib/II study of XL184 (BMS 907351) with and without erlotinib (E) in patients (pts) with non-small cell lung cancer (NSCLC). J Clin Oncol 2010, 28(Suppl.). Abstract 3017.
109. Genentech. A randomized, phase III, multicenter, double-blind, placebo-controlled study evaluating efficacy and safety of onartuzumab (MetMab) in combination with Tarceva (erlotinib) in patients with Met diagnostic-positive non-small cell lung cancer who have received standard chemotherapy for advanced/metastatic disease; 2012. Accessed November 5, 2012. http://clinicaltrials.gov/ct2/show/NCT01456325.
110. Pfizer Inc. Xalkori (crizotinib) capsules, oral; prescribing information; February 2012. Accessed November 5, 2012. http://labeling.pfizer.com/showlabeling.aspx?id=676.
111. Ou S.H., Kwak E.L., Siwak-Tapp C., et al. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac Oncol 2011, 6:942-946.
112. Lennerz J.K., Kwak E.L., Ackerman A., et al. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol 2011, 29:4803-4810.
113. Giordano S. Rilotumumab, a mAb against human hepatocyte growth factor for the treatment of cancer. Curr Opin Mol Ther 2009, 11:448-455.
114. Tuma R.S. Rilotumumab combination shows higher response rate in metastatic colorectal cancer patients. Oncology Times 2011, 8:7.
115. Van Cutsem E., Eng C., Tabernero J., et al. A randomized, phase I/II trial of AMG 102 or AMG 479 in combination with panitumumab (pmab) compared with pmab alone in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC): safety and efficacy results [oral]. J Clin Oncol 2011, 29(Suppl.). Abstract 366.
116. Iveson T., Donehower R.C., Davidenko I., et al. Safety and efficacy of epirubicin, cisplatin, and capecitabine (ECX) plus rilotumumab (R) as first-line treatment for unresectable locally advanced (LA) or metastatic (M) gastric or esophagogastric junction (EGJ) adenocarcinoma [oral]. Eur J Cancer 2011, 47(Suppl. 1):S443. Abstract 6504.
117. Ryan C.J., Rosenthal M., Ng S., et al. A multicenter, randomized phase II study of rilotumumab (R) (AMG 102) or placebo (Pbo) plus mitoxantrone (M) and prednisone (P) in patients (pts) with previously treated castrate-resistant prostate cancer (CRPC) [poster]. J Clin Oncol 2012, 30(Suppl.). Abstract 115.
118. Schoffski P., Garcia J.A., Stadler W.M., et al. A phase II study of the efficacy and safety of AMG 102 in patients with metastatic renal cell carcinoma. BJU Int 2011, 108:679-686.
119. Wen P.Y., Schiff D., Cloughesy T.F., et al. A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma. Neuro Oncol 2011, 13:437-446.
120. Oliner K.S., Tang R., Anderson A., et al. Evaluation of MET pathway biomarkers in a phase II study of rilotumumab (R, AMG 102) or placebo (P) in combination with epirubicin, cisplatin, and capecitabine (ECX) in patients (pts) with locally advanced or metastatic gastric (G) or esophagogastric junction (EGJ) cancer. J Clin Oncol 2012, 30(Suppl.). Abstract 4005.
121. Amgen. A phase 1b/2 trial of AMG 479 or AMG 102 in combination with platinum-based chemotherapy as first-line treatment for extensive stage small cell lung cancer; 2011. Accessed November 5, 2012. http://clinicaltrials.gov/ct2/show/NCT00791154.
122. University of Pittsburgh; Amgen. A phase I/II trial of AMG 102 and erlotinib in previously treated patients with advanced non-small cell lung cancer; 2012. Accessed November 5, 2012. http://clinicaltrials.gov/ct2/show/NCT01233687.
123. AVEO Pharmaceuticals. A phase 1b/2 study of AV-299 (formerly SCH 900105) in combination with gefitinib in Asian subjects with non-small cell lung cancer (P06162); 2012. Accessed November 5, 2012. http://clinicaltrials.gov/ct2/show/NCT01039948.
124. Mok T., Tan E., Park K., et al. Randomized phase II study of ficlatuzumab (formerly AV-299), an anti-hepatocyte growth factor (HGF) monoclonal antibody (MAb) in combination with gefitinib (G) in Asian patients (pts) with NSCLC. J Clin Oncol 2011, 29(Suppl.). Abstract TPS213.