A phase II and biomarker study of ramucirumab, a human monoclonal antibody targeting the VEGF receptor-2, as first-line monotherapy in patients with advanced hepatocellular Cancer

Clinical Cancer Research

Volumn 19, Issue 23, 2013, Pages 6614-6623

  Zhu, Andrew X ^a   Finn, Richard S ^b   Mulcahy, Mary ^c   Gurtler, Jayne ^d   Sun, Weijing ^e   Schwartz, Jonathan D ^f   Dalal, Rita P ^f   Joshi, Adarsh ^f   Hozak, Rebecca R ^f   Xu, Yihuan ^f   Ancukiewicz, Marek ^a   Jain, Rakesh K ^a   Nugent, Francis W ^g   Duda, Dan G ^a   Stuart, Keith ^g  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c NORTHWESTERN UNIVERSITY   (United States)

^d East Jefferson General Hospital   (United States)

^e UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^f ELI LILLY AND COMPANY   (United States)

^g TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PLACENTAL GROWTH FACTOR; RAMUCIRUMAB; TUMOR MARKER; VASCULOTROPIN; VASCULOTROPIN RECEPTOR 2;

ADULT; ADVANCED CANCER; AGED; ANOREXIA; ARTICLE; ASCITES; BACKACHE; BRAIN DISEASE; CANCER STAGING; CHILD PUGH SCORE; CLINICAL ARTICLE; CONTROLLED STUDY; DIARRHEA; DISEASE COURSE; DISEASE MARKER; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; DRUG SAFETY; DRUG WITHDRAWAL; FATIGUE; FEMALE; GASTROINTESTINAL HEMORRHAGE; GRAM NEGATIVE SEPSIS; HEADACHE; HEPATIC ENCEPHALOPATHY; HEPATORENAL SYNDROME; HUMAN; HYPERBILIRUBINEMIA; HYPERTENSION; HYPOMAGNESEMIA; HYPONATREMIA; INFUSION RELATED REACTION; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FAILURE; MALE; MIDDLE AGED; MUSCULOSKELETAL PAIN; NAUSEA; OBJECTIVE RESPONSE RATE; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN BLOOD LEVEL; THORAX PAIN; THROMBOCYTOPENIA; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CARCINOMA, HEPATOCELLULAR; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; LIVER NEOPLASMS; MALE; MIDDLE AGED; PREGNANCY PROTEINS; PROPORTIONAL HAZARDS MODELS; TUMOR MARKERS, BIOLOGICAL; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 84890287907     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-1442     Document Type: Article

References (33)

1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90.
2. 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.
3. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011;473:298-307.
4. Ferrara N, Gerber HP, Le Couter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-76.
5. Zhu AX, Duda DG, Sahani DV, Jain RK. HCC and angiogenesis: possible targets and future directions. Nat Rev Clin Oncol 2011;8:292-301.
6. Graepler F, Verbeek B, Graeter T, Smirnow I, Kong HL, Schuppan D, et al. Combined endostatin/sFlt-1 antiangiogenic gene therapy is highly effective in a rat model of HCC. Hepatology 2005;41:879-86.
7. Lu D, Shen J, Vil MD, Zhang H, Jimenez X, Bohlen P, et al. Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J Biol Chem 2003;278:43496-507.
8. Bruns CJ, Liu W, Davis DW, Shaheen RM, McConkey DJ, Wilson MR, et al. Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases. Cancer 2000;89:488-99.
9. Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S, et al. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 2010;28:780-7.
10. Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) Investigators. Hepatology 2000;31:840-5.
11. Child CG, Turcotte JG. Surgery and portal hypertension, in Child CG, editor. The liver and portal hypertension. Philadelphia, PA: Saunders; 1964. p. 50-64.
12. Pugh R N H, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophagealvarices. Br J Surg 1973;60:646-9.
13. Zhu AX, Sahani DV, Duda DG, Di Tomaso E, Ancukiewicz M, Catalano OA, et al. Efficacy, safety, and potential biomarkers of sunitinibmonotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 2009;27:3027-35.
14. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003;42:1206-52.
15. Mackey J, Gelmon K, Martin M, McCarthy N, Pinter T, Rupin M, Youssoufian H. TRIO-012: A multicenter, multinational, randomized, double-blind phase III study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer. Clin Breast Cancer 2009;9:258-61.
16. Zhu AX, Chau I, Blanc JF, Okusaka T, Rojas M, Yang L, et al. A multicenter, randomized, double-blind, phase 3 study of ramucirumab (IMC-1121B; RAM) and best supportive care (BSC) versus placebo (PBO) and BSC as second-line treatment in patients (pts) with hepatocellular carcinoma (HCC) following first-line therapy with sorafenib (SOR). J Clin Oncol 2012;30(suppl): AbstractTPS4146.
17. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2013 Oct. 1. pii: S0140-6736 (13) 61719-5. doi: 10.1016/S0140-6736 (13) 61719-5. [Epub ahead of print]
18. Wilke H, Cunningham D, Ohtsu A, Nuber U, Bruns R, Schmitt-Bormann B. A randomized, multicenter, double-blind, placebo (PBO)-controlled phase 3 study of paclitaxel (PTX) with or without ramucirumab (IMC-1121B; RAM) in patients (pts) with metastatic gastric adenocarcinoma, refractory to or progressive after first-line therapy with platinum (PLT) and fluoropyrimidine (FP). J Clin Oncol 2012;30(suppl):Abstract TPS4139.
19. Garon EB, Cao D, Alexandris E, John WJ, Yurasov S, Perol M. A randomized, double-blind, phase III study of docetaxel and ramucirumab versus docetaxel and placebo in the treatment of stage IV non-small-cell lung cancer after disease progression after 1 previous platinum-based therapy (REVEL): Treatment Rationale and Study Design. Clin Lung Cancer 2012;13:505-9.
20. Cheng A, Kang Y, Lin D, Park M, Kudo S, Qin M, et al. Phase III trial of sunitinib (Su) versus sorafenib (So) in advanced hepatocellular carcinoma (HCC). J Clin Oncol 2011;29(suppl):Abstract 4000.
21. Cainap C, Qin S, Huang W-T, Chung IJ, Pan H, Cheng Y, et al. Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol 2012;30(suppl 34):Abstract249.
22. Johnson P, Qin S, Park J-W. Brivanib (BRI) versus sorafenib (SOR) as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma (HCC): results from the randomized phase 3 BRISK-FL study. J Clin Oncol 2013;31:3517-24.
23. 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;31:3509-16.
24. Scartozzi M, Galizia E, Chiorrini S, Giampieri R, Berardi R, Pierantoni C, et al. Arterialhypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol 2009;20:227-30.
25. Martin LK, Li X, Kleiber B, Ellison EC, Bloomston M, Zalupski M, et al. VEGF remains an interesting target in advanced pancreas cancer (APCA): results of a multi-institutional phase II study of bevacizumab, gemcitabine, and infusional 5-fluorouracil in patients with APCA. Ann Oncol 2012;23:2812-20.
26. Rutkowski P, Bylina E, Klimczak A. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure - one institution study. BMC Cancer 2012;12:107.
27. De Stefano A, Carlomagno C, Pepe S, Bianco R, De Placido S. Bevacizumab-related arterial hypertension as a predictive marker in metastatic colorectal cancer patients. Cancer Chemother Pharmacol 2011;68:1207-13.
28. George S, Reichardt P, Lechner T. Hypertension as a potential biomarker of efficacy in patients with gastrointestinal stromal tumor treated with sunitinib. Ann Oncol 2012;23:3180-7.
29. Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 2008;26:4672-8.
30. Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response and other comparisons of time-to-event by outcome variables. J Clin Oncol 2008;26:3913-5.
31. Jain RK, Duda DG, Willett CG, Sahani DV, Zhu AX, Loeffler JS, et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 2009;6:327-38.
32. Zhu AX, Ancukiewicz M, Supko JG, Sahani DV, Blaszkowsky LS, Meyerhardt JA, et al. Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study. Clin Cancer Res 2013;19:1557-66.
33. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008;100:698-711.