Aflibercept in the treatment of patients with metastatic colorectal cancer: Latest findings and interpretations

Therapeutic Advances in Gastroenterology

Volumn 6, Issue 6, 2013, Pages 459-473

  Tang, Patricia A ^a   Moore, Malcom J ^b  

^a TOM BAKER CANCER CENTRE   (Canada)

^b PRINCESS MARGARET HOSPITAL   (Canada)

Author keywords

aflibercept; angiogenesis; metastatic colorectal cancer

Indexed keywords

AFLIBERCEPT; BEVACIZUMAB; CAPECITABINE; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; OXALIPLATIN; REGORAFENIB; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3;

ABDOMINAL PAIN; ANEMIA; ANTIANGIOGENIC ACTIVITY; ANTIANGIOGENIC THERAPY; ARTHRALGIA; ASTHENIA; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CONSTIPATION; COST EFFECTIVENESS ANALYSIS; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DYSPHONIA; EPISTAXIS; FEBRILE NEUTROPENIA; HAND FOOT SYNDROME; HEADACHE; HUMAN; HYPERTENSION; INFECTION; METASTATIC COLORECTAL CANCER; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; RECTUM ULCER; REVIEW; STOMATITIS; THROMBOCYTOPENIA; THROMBOEMBOLISM; VOMITING; WOUND HEALING IMPAIRMENT;

EID: 84888098804     PISSN: 1756283X     EISSN: 17562648     Source Type: Journal    
DOI: 10.1177/1756283X13502637     Document Type: Article

References (51)

1. Arnold D. Andre T. Bennouna J. Sastre J. Osterlund P. Greil R. et al. (2012) Bevacizumab (BEV) plus Chemotherapy (CT) continued beyond first progression in patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus CT: results of a randomized phase III intergroup study (TML study). ASCO Meeting Abstracts 30: CRA3503.
2. Bergers G. Hanahan D. (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8: 592–603.
3. Carmeliet P. (2005) Angiogenesis in life, disease and medicine. Nature 438: 932–936.
4. Chiron M. Vrignaud P. Lejeune P. Demers B. Leopold W. Bissery M. (2007) Synergistic activity of aflibercept (VEGF Trap) in combination with 5-fluorouracil and irinotecan in preclinical tumor models. AACR Meeting Abstracts. San Francisco, CA, 22–26 October 2007: abstract A13.
5. Ciombor K. Berlin J. Chan E. (2013) Aflibercept. Clin Cancer Res 19: 1920–1925.
6. Dixon J. Oliver S. Olson J. Mandava N. (2009) VEGF Trap-Eye for the treatment of neovascular age-related macular degeneration. Expert Opin Investig Drugs 18: 1573–1580.
7. Ellis L. Hicklin D. (2008) VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 8: 579–591.
8. Escudero-Esparza A. Martin T. Davies M. Jiang W. (2009) PGF isoforms, PLGF-1 and PGF-2, in colorectal cancer and the prognostic significance. Cancer Genomics Proteomics 6: 239–246.
9. Ferlay J. Shin H. Bray F. Forman D. Mathers C. Parkin D. (2010) GLOBOCAN 2008 V2.0, cancer incidence and mortality worldwide: IARC CancerBase No. 10 [Internet], Vol. 2013. Lyon, France: International Agency for Research on Cancer.
10. Ferrara N. Hillan K. Gerber H. Novotny W. (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3: 391–400.
11. Fischer C. Jonckx B. Mazzone M. Zacchigna S. Loges S. Pattarini L. et al. (2007) Anti-PLGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131: 463–475.
12. Fischer C. Mazzone M. Jonckx B. Carmeliet P. (2008) FLT 1 and its ligands VEGFB and PIGF: drug targets for anti-angiogenic therapy? Nat Rev Cancer 8: 942–956.
13. Folkman J. (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1: 27–31.
14. Folkman J. (2003) Fundamental concepts of the angiogenic process. Curr Mol Med 3: 643–651.
15. Fukumura D. Duda D. Munn L. Jain R. (2010) Tumor microvasculature and microenvironment: novel insights through intravital imaging in pre-clinical models. Microcirculation 17: 206–225.
16. Giantonio B. Catalano P. Meropol N. O'Dwyer P. Mitchell E. Alberts S. et al. (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25: 1539–1544.
17. Gomez-Manzano C. Holash J. Fueyo J. Xu J. Conrad C. Aldape K. et al. (2008) VEGF Trap induces antiglioma effect at different stages of disease. Neuro Oncol 10: 940–945.
18. Grothey A. van Cutsem E. Sobrero A. Siena S. Falcone A. Ychou M. et al. (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (correct): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381: 303–312.
19. Holash J. Davis S. Papadopoulos N. Croll S. Ho L. Russell M. et al. (2002) VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 99: 11393–11398.
20. Hurwitz H. Douglas P. Middleton J. Sledge G. Johnson D. Reardon D. et al. (2013) Analysis of early hypertension and clinical outcome with bevacizumab: results from seven phase III studies. Oncologist 18: 273–280.
21. Hurwitz H. Fehrenbacher L. Hainsworth J. Heim W. Berlin J. Holmgren E. et al. (2005) Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 23: 3502–3508.
22. Hurwitz H. Fehrenbacher L. Novotny W. Cartwright T. Hainsworth J. Heim W. et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–2342.
23. Hurwitz H. Saltz L. van Cutsem E. Cassidy J. Wiedemann J. Sirzen F. et al. (2011) Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol 29: 1757–1764.
24. Jain R. (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307: 58–62.
25. Jain R. Duda D. Willett C. Sahani D. Zhu A. Loeffler J. et al. (2009) Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 6: 327–338.
26. Kabbinavar F. Schulz J. McCleod M. Patel T. Hamm J. Hecht J. et al. (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23: 3697–3705.
27. Khayat D. Tejpar S. Spano J. Verslype C. Bloch J. Vandecaveye V. et al. (2013) Intravenous aflibercept administered in combination with irinotecan, 5-fluorouracil and leucovorin in patients with advanced solid tumours: results from the expansion cohort of a phase I study. Eur J Cancer 49: 790–797.
28. Kim E. Serur A. Huang J. Manley C. McCrudden K. Frischer J. et al. (2002) Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma. Proc Natl Acad Sci U S A 99: 11399–11404.
29. Kopetz S. Hoff P. Morris J. Wolff R. Eng C. Glover K. et al. (2010) Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer: efficacy and circulating angiogenic biomarkers associated with therapeutic resistance. J Clin Oncol 28: 453–459.
30. Lambrechts D. Lenz H. de Haas S. Carmeliet P. Scherer S. (2013) Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 31: 1219–1230.
31. Limentani S. Just R. Purdham A. Mulay M. Bair A. Tamby J. et al. (2008) A phase I dose escalation and pharmacokinetic (PK) study of intravenous (IV) aflibercept (VEGF Trap) plus FOLFOX 4 in patients (Pts) with advanced solid tumors: preliminary results. ASCO Meeting Abstracts 26: 3556.
32. Lockhart A. Rothenberg M. Dupont J. Cooper W. Chevalier P. Sternas L. et al. (2010) Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol 28: 207–214.
33. Loupakis F. Cremolini C. Fioravanti A. Orlandi P. Salvatore L. Masi G. et al. (2011) Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line Folfoxiri plus bevacizumab schedule in metastatic colorectal cancer. Br J Cancer 104: 1262–1269.
34. Morlock R. Yu E. Ray J. (2013) A cost-effectiveness analysis of bevacizumab (BV) plus chemotherapy (CT) versus aflibercept (AFLI) plus CT in patients with metastatic colorectal cancer (mCRC) previously treated with BV. ASCO Meeting Abstracts 31: 417.
35. Nalluri S. Chu D. Keresztes R. Zhu X. Wu S. (2008) Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300: 2277–2285.
36. O'Connor J. Carano R. Clamp A. Ross J. Ho C. Jackson A. et al. (2009) Quantifying antivascular effects of monoclonal antibodies to vascular endothelial growth factor: insights from imaging. Clin Cancer Res 15: 6674–6682.
37. Pericay C. Folprecht G. Saunders M. Thomas A. Roh J. Lopez R. et al. (2012) Phase 2 randomized, noncomparative open-label study of aflibercept and modified FOLFOX 6 in the first line treatment of metastatic colorectal cancer (AFFIRM). Ann Oncol 23(Suppl. 4): iv16, abstract 0024.
38. Rudge J. Holash J. Hylton D. Russell M. Jiang S. Leidich R. et al. (2007) Inaugural article: VEGF trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc Natl Acad Sci U S A 104: 18363–18370.
39. Saltz L. Clarke S. Diaz-Rubio E. Scheithauer W. Figer A. Wong R. et al. (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26: 2013–2019.
40. Sanoff H. Sargent D. Campbell M. Morton R. Fuchs C. Ramanathan R. et al. (2008) Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol 26: 5721–5727.
41. Scappaticci F. Skillings J. Holden S. Gerber H. Miller K. Kabbinavar F. et al. (2007) Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 99: 1232–1239.
42. Tang P. Cohen S. Kollmannsberger C. Bjarnason G. Virik K. Mackenzie M. et al. (2012) Phase II clinical and pharmacokinetic study of aflibercept in patients with previously treated metastatic colorectal cancer. Clin Cancer Res 18: 6023–6031.
43. Tofts P. Brix G. Buckley D. Evelhoch J. Henderson E. Knopp M. et al. (1999) Estimating kinetic parameters from dynamic contrast-enhanced T (1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10: 223–232.
44. Tournigand C. Andre T. Achille E. Lledo G. Flesh M. Mery-Mignard D. et al. (2004) FOLFIRI followed by FOLFOX 6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22: 229–237.
45. van Cutsem E. Tabernero J. Lakomy R. Prenen H. Prausova J. Macarulla T. et al. (2012) Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30: 3499–3506.
46. van Cutsem E. Tabernero J. Lakomy R. Rausova J. Ruff P. van Hazel G. et al. (2011) Intravenous (IV) aflibercept versus placebo in combination with irinotecan/5-FU (FOLFIRI) for second line treatment of metastatic colorectal cancer (mCRC): results of a multinational phase III trial (EFC10262-VELOUR). Ann Oncol 22: v18 (abstract O-0024).
47. Willett C. Duda D. Di Tomaso E. Boucher Y. Ancukiewicz M. Sahani D. et al. (2009) Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 27: 3020–3026.
48. Wu S. Kim C. Baer L. Zhu X. (2010) Bevacizumab increases risk for severe proteinuria in cancer patients. J Am Soc Nephrol 21: 1381–1389.
49. Yang W. Ahn H. Hinrichs M. Torry R. Torry D. (2003) Evidence of a novel isoform of placenta growth factor (PlGF-4) expressed in human trophoblast and endothelial cells. J Reprod Immunol 60: 53–60.
50. Yao J. Wu X. Zhuang G. Kasman I. Vogt T. Phan V. et al. (2011) Expression of a functional VEGFR-1 in tumor cells is a major determinant of Anti-PLGF antibodies efficacy. Proc Natl Acad Sci U S A 108: 11590–11595.
51. Yoshino T. Yamazaki K. Yamaguchi K. Doi T. Boku N. Machida N. et al. (2012) A phase I study of intravenous aflibercept with FOLFIRI in Japanese patients with previously treated metastatic colorectal cancer. Invest New Drugs 31: 910-917.