Ramucirumab: Preclinical research and clinical development

OncoTargets and Therapy

Volumn 7, Issue , 2014, Pages 1997-2006

  Aprile, Giuseppe ^a   Rijavec, Erika ^b   Fontanella, Caterina ^a   Rihawi, Karim ^a   Grossi, Francesco ^b  

^a UNIVERSITY HOSPITAL OF UDINE   (Italy)

^b UNIVERSITY OF GENOA   (Italy)

Author keywords

Antiangiogenic; Breast cancer; Gastric cancer; Lung cancer; Ramucirumab

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTHRACYCLINE; BEVACIZUMAB; CAPECITABINE; CARBOPLATIN; CISPLATIN; DOCETAXEL; ERIBULIN; FLUOROPYRIMIDINE; FLUOROURACIL; FOLINIC ACID; ICRUCUMAB; IRINOTECAN; OXALIPLATIN; PACLITAXEL; PEMETREXED; PLACEBO; RAMUCIRUMAB; SORAFENIB; TAXANE DERIVATIVE; VASCULOTROPIN RECEPTOR 2;

ABDOMINAL PAIN; ADVANCED CANCER; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; BACKACHE; BLEEDING; BREAST METASTASIS; COLORECTAL CANCER; COLORECTAL CARCINOMA; CONGESTIVE HEART FAILURE; CONSTIPATION; COUGHING; DIARRHEA; DRUG BINDING; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DESIGN; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; EPISTAXIS; ESOPHAGUS CANCER; FATIGUE; FEBRILE NEUTROPENIA; GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA; GASTROESOPHAGEAL JUNCTION CARCINOMA; HEADACHE; HUMAN; HYPERTENSION; LEIOMYOSARCOMA; LEUKOPENIA; LIVER CELL CARCINOMA; LUNG CANCER; MAINTENANCE THERAPY; MELANOMA; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NON SMALL CELL LUNG CANCER; NONHUMAN; OVARY CARCINOMA; OVERALL SURVIVAL; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STOMACH CANCER; STOMATITIS; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION; UTERINE LEIOMYOSARCOMA; VEIN THROMBOSIS;

EID: 84908282604     PISSN: 11786930     EISSN: 11786930     Source Type: Journal    
DOI: 10.2147/OTT.S61132     Document Type: Review

References (49)

1. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23(5): 1011-1027
2. Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358(19): 2039-2049
3. Limaverde-Sousa G, Sternberg C, Ferreira CG. Antiangiogenesis beyond VEGF inhibition: a journey from antiangiogenic singletarget to broad-spectrum agents. Cancer Treat Rev. 2014;40(4): 548-557
4. Schneider BP, Shen F, Miller KD. Pharmacogenetic biomarkers for the prediction of response to antiangiogenic treatment. Lancet Oncol. 2012;13(10):e427-e436
5. Lambrechts D, Lenz HJ, de Haas S, Carmeliet P, Scherer SJ. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol. 2013;31(9):1219-1230
6. Tocchetti CG, Gallucci G, Coppola C, et al. The emerging issue of cardiac dysfunction induced by antineoplastic angiogenesis inhibitors. Eur J Heart Fail. 2013;15(5):482-489
7. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9(6):669-676
8. Youssoufian H, Hicklin DJ, Rowinsky EK. Review: monoclonal anti bodies to the vascular endothelial growth factor receptor-2 in cancer therapy. Clin Cancer Res. 2007;13(18 Pt 2):5544s-5548s
9. Aprile G, Bonotto M, Ongaro E, at al. Critical appraisal of ramucirumab (IMC-1121B) for cancer treatment: from benchside to clinical use. Drugs. 2013;73:2003-2015
10. Lu D, Jimenez X, Zhang H, et al. Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy. Int J Cancer. 2002;97(3):393-399
11. Miao HQ, Hu K, Jimenez X, et al. Potent neutralization of VEGF biological activities with a fully human antibody Fab fragment directed against VEGF receptor 2. Biochem Biophys Res Commun. 2006;345(1): 438-445
12. Poone RM, Vaidya A. Ramucirumab: first global approval. Drugs. 2014;74(9):1047-1058
13. Prewett M, Huber J, Li Y, et al. Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res. 1999;59:5209-5218
14. Bruns CJ, Liu W, Davis DW, 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;89:488-499
15. Zhu Z, Hattori K, Zhang H, et al. Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth facto receptor 2. Correlation between antibody affinity and biological activity. Leukemia. 2003;17:604-611
16. Clarke JM, Hurwitz HI. Targeted inhibition of VEGF receptor 2: an update on ramucirumab. Expert Opin Biol Ther. 2013;13(8):1187-1196
17. Spratlin JL, Cohen RB, Eadens M, 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;28:780-787
18. Fuchs CS, Tomasek J, Yong CJ, 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. 2014;383(9911):31-39
19. Safran H, Tomasek J, Yong CJ, et al. REGARD: a phase 3, randomized, double-blind trial of ramucirumab and best supportive care versus placebo and BSC in the treatment of metastatic gastric or gastroesophageal junction adenocarcinoma following disease progression on first-line platinum and/or fluoropyrimidine-containing combination therapy: age subgroup analysis. ASCO Annual Meeting; 2014
20. Wilke H, Van Cutsem E, Oh SC, et al. RAINBOW: a global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE). Gastrointestinal Cancers Symposium; 2014
21. Wilke H, Van Cutsem E, Oh SC, et al. RAINBOW: a global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum and fluoropyrimidine-containing combination therapy: results of a multivariate Cox regression analysis adjusting for prognostic factors. ASCO Annual Meeting; 2014:abstract 4076
22. Van Cutsem E, Clingan P, Ananda S, et al. RAINBOW: a global, phase 3, double-blind study of ramucirumab (RAM) plus paclitaxel (PTX) versus placebo (PL) + PTX in the treatment of advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line platinum-and fluoropyrimidine-containing combination therapy: a subgroup analysis of Western population. ASCO Annual Meeting; 2014
23. Al-Batran SH, Van Cutsem E, Oh SC, et al. RAINBOW: a global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction (GEJ) adenocarcinoma quality-of-life (QoL) results. ASCO Annual Meeting; 2014:abstract 4058
24. Yoon HH, Bendell JC, Fadi SB, et al. Ramucirumab (RAM) plus FOLFOX as front-line therapy (Rx) for advanced gastric or esophageal adenocarcinoma (GE-AC): randomized, double-blind, multicenter phase 2 trial. Presented at ASCO 2014 Annual Meeting. J Clin Oncol. 2014;325:abstract 4004
25. Eli Lilly and Company. A study of ramucirumab (IMC-1121B) drug product (DP) and best supportive care (BSC) versus placebo and BSC as 2nd-line treatment in patients with hepatocellular carcinoma after 1st-line therapy with sorafenib (REACH). http://www.clinicaltrials.gov/ct2/show/NCT01140347?term=NCT01140347&rank=1.NLM identifier: NCT01140347. Accessed September 25, 2014
26. Eli Lilly and Company. A study in second line metastatic colorectal cancer.http://www.clinicaltrials.gov/ct2/show/NCT01183780?term=NCT01183780&rank=1.NLM identifier:NCT01183780. Accessed September 25, 2014
27. Grothey A, Tabernero J, Rougier P, A randomized, double blind, phase (Ph) III study of the irinotecan-based chemotherapy FOLFIRI plus ramucirumab (RAM) or placebo (PL) in patients (pts) with metastatic colorectal carcinoma (mCRC) progressive during or following first-line therapy with bevacizumab (BEV), oxaliplatin (OXALI), and a fluoropyrimidine (FP) (RAISE) (NCT01183780). 2014 ASCO Annual Meeting. J Clin Oncol. 2012;30(Suppl):abstract TPS3634
28. Zhu AX, Chau I, Blanc J-F, et al. A multicenter, randomized, double blind, phase III 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). 2012 ASCO Annual Meeting. J Clin Oncol. 2012;30(Suppl):abstract TPS4146. NCT01140347
29. Camidge DR, Ballas MS, Dubey S, A phase II, open-label study of ramucirumab (IMC-1121B), an IgG1 fully human monoclonal antibody (Mab) targeting VEGFR-2, in combination with paclitaxel and carboplatin as first-line therapy in patients (pts) with stage IIIb/IV non-small cell lung cancer (NSCLC). J Clin Oncol. 2010; 28(Suppl):7588
30. Doebele RC, Spigel D, Tehfe M, et al. A phase 2 randomized openlabel study of ramucirumab (IMC 1121B; RAM) in combination with first-line platinum-based chemotherapy in patients (pts) with recurrent or advanced non-small cell lung cancer (NSCLC): final results from non-squamous (NSQ) pts. J Thorac Oncol. 2013;8:S290
31. 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;13:505-509
32. Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomized phase 3 trial. Lancet. 2014;384(9944):665-673
33. Eli Lilly and Company. An open-label, multicenter, randomized, phase 2 study of a recombinant human anti-VEGFR-2 monoclonal antibody, IMC-1121B in combination with platinum-based chemotherapy versus platinum-based chemotherapy alone as first-line treatment of patients with recurrent or advanced non-small cell lung cancer (NSCLC). Available from: http://clinicaltrials.gov/show/NCT01160744.NLMidentifier:NCT01160744. Accessed September 25, 2014
34. Eli Lilly and Company. A randomized, double-blind, phase 2 study of docetaxel and ramucirumab versus docetaxel and placebo in the treatment of stage IV non-small cell lung cancer following disease progression after one prior platinum-based therapy. Available from: http://clinicaltrials.gov/show/NCT01703091.NLM identifier: NCT01703091. Accessed September 25, 2014
35. Aesoy R, Sanchez BC, Norum JH, Lewensohn R, Viktorsson K, Linderholm B. An autocrine VEGF/VEGFR2 and p38 signaling loop confers resistance to 4-hydroxytamoxifen in MCF-7 breast cancer cells. Mol Cancer Res. 2008;6:1630-1638
36. Ghosh S, Sullivan CA, Zerkowski MP, et al. High levels of vascular endothelial growth factor and its receptors (VEGFR-1, VEGFR-2, neuropilin-1) are associated with worse outcome in breast cancer. Hum Pathol. 2008;39:1835-1843
37. Skobe M, Rockwell P, Goldstein N, Vosseler S, Fusenig NE. Blocking angiogenesis results in tumor cell invasion suppression. Nat Med. 1997;3:1222-1227
38. Konecny GE, Meng YG, Untch M, et al. Association between HER-2/ neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res. 2004;10: 1706-1716
39. Price DJ, Miralem T, Jiang S, Steinberg R, Avraham H. Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ. 2001;12: 129-135
40. O’Sullivan Coyne G, Burotto Pichun M. Clinical experience with ramucirumab: outcomes in breast cancer. Exp Opin Biol Ther. 2014;14(9): 1351-1360
41. Eli Lilly and Company. A study of ramucirumab (IMC-1121B) in participants with breast cancer. Available from: http://clinicaltrials.gov/ct2/show/results/NCT01256567.NLMidentifier: NCT01256567. Accessed September 25, 2014
42. Hotchkiss KA, Ashton AW, Sparano J, et al. Inhibition of endothelial cell function by docetaxel (Taxotere). Proc Am Assoc Cancer Res. 2000;41:647
43. Miles DW, Chan A, Dirix LY, et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010;28:3239-3247
44. Yardley DA, Richards PD, Reeves JA, et al. Final results of a phase 2 study of ramucirumab (RAM) plus eribulin (E) versus E in advanced metastatic breast cancer (MBC). J Clin Oncol. 2014;32(Suppl): abstract 1035
45. Eli Lilly and Company. Study of IMC-18F1 or ramucirumab DP in combination with capecitabine or capecitabine on previously treated breast cancer patients. Available from: http://clinicaltrials. gov/show/NCT01234402.NLM identifier: NCT01234402. Accessed September 25, 2014
46. Mackey JR, Ramos-Vazquez M, Lipatov O, et al. Primary results of ROSE/TRIO-12, a randomized placebo controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer. Available from: http://www.abstracts2view. com/sabcs13/view.php?nu=SABCS13L_238. Accessed September 25, 2014
47. Miles DW, de Haas SL, Dirix LY, et al. Biomarker results from the AVADO phase 3 trial of first-line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer. Br J Cancer. 2013;19;108(5): 1052-1060
48. Ellis LM. American Society of Clinical Oncology perspective: raising the bar for clinical trials by defining clinically meaningful outcomes. J Clin Oncol. 2014;32(12):1277-1280.
49. Reck M, Kaiser M, Mellemgaard A, et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014;15(2):143-155.