The evolving role of VEGF-targeted therapies in the treatment of metastatic colorectal cancer

Expert Review of Anticancer Therapy

Volumn 13, Issue 4, 2013, Pages 427-438

  Fakih, Marwan ^a  

^a City of Hope   (United States)

Author keywords

aflibercept; angiogenesis; antiangiogenesis; bevacizumab; colorectal cancer; metastatic colorectal cancer; VEGF

Indexed keywords

AFLIBERCEPT; BEVACIZUMAB; CAPECITABINE; CD34 ANTIGEN; CETUXIMAB; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; MITOMYCIN; OXALIPLATIN; PANITUMUMAB; PLACEBO; PLACENTAL GROWTH FACTOR; VASCULOTROPIN A; VASCULOTROPIN B; VASCULOTROPIN C; VASCULOTROPIN D; VASCULOTROPIN RECEPTOR 1; VASCULOTROPIN RECEPTOR 2; VASCULOTROPIN RECEPTOR 3;

ABDOMINAL PAIN; ANOREXIA; ANTIANGIOGENIC THERAPY; ARTERIAL THROMBOEMBOLISM; ASTHENIA; BINDING AFFINITY; BLEEDING; CANCER COMBINATION CHEMOTHERAPY; CANCER REGISTRY; CANCER SURVIVAL; COLORECTAL CANCER; DEHYDRATION; DIARRHEA; DRUG BINDING; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG INDUCED DISEASE; DRUG MECHANISM; DRUG RESPONSE; DRUG SAFETY; DRUG SPECIFICITY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; GENOTYPE; HOARSENESS; HUMAN; HYPERTENSION; INFECTION; INTESTINE PERFORATION; LEUKOPENIA; LIGAND BINDING; LOW DRUG DOSE; LUNG EMBOLISM; METASTATIC COLORECTAL CANCER; MOLECULAR DYNAMICS; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; NAUSEA; NEUROPATHY; NEUTROPENIA; NONHUMAN; OVERALL SURVIVAL; PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECTUM CARCINOMA; RETROSPECTIVE STUDY; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN DISEASE; SKIN TOXICITY; STOMATITIS; SURVIVAL RATE; VOMITING;

ANGIOGENESIS INHIBITORS; ANIMALS; COLORECTAL NEOPLASMS; HUMANS; MOLECULAR TARGETED THERAPY; NEOVASCULARIZATION, PATHOLOGIC; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84876153459     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.13.20     Document Type: Review

References (71)

1. Adam R, Haller DG, Poston G et al. Toward optimized front-line therapeutic strategies in patients with metastatic colorectal cancer - an expert review from the International Congress on Anti-Cancer Treatment (ICACT) 2009. Ann. Oncol. 21(8), 1579-1584 (2010)
2. Korpanty G, Sullivan LA, Smyth E, Carney DN, Brekken RA. Molecular and clinical aspects of targeting the VEGF pathway in tumors. J. Oncol. doi:10.1155/2010/652320 (2010) (Epub ahead of print
3. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1(1), 27-31 (1995
4. Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 65(3), 671-680 (2005)
5. Ferrara N, Hillan KJ, Novotny W. Bevacizumab (Avastin), a humanized anti- VEGF monoclonal antibody for cancer therapy. Biochem. Biophys. Res. Commun. 333(2), 328-335 (2005)
6. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350(23), 2335-2342 (2004)
7. Chu QS. Aflibercept (AVE0005): an alternative strategy for inhibiting tumour angiogenesis by vascular endothelial growth factors. Expert. Opin. Biol. Ther. 9(2), 263-271 (2009)
8. Cao Y. Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci. Signal. 2(59), re1 (2009)
9. Teng LS, Jin KT, He KF, Zhang J, Wang HH, Cao J. Clinical applications of VEGFtrap (aflibercept) in cancer treatment. J. Chin. Med. Assoc. 73(9), 449-456 (2010)
10. Van Cutsem E, Tabernero J, Lakomy R et al. 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(28), 3499-3506 (2012)
11. Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 8(8), 592-603 (2008)
12. Jain RK, Duda DG, Willett CG et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat. Rev. Clin. Oncol. 6(6), 327-338 (2009)
13. Arnold D, Andre T, Bennouna J et al. 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). Presented at: 2012 Annual Meeting of the American Society of Clinical Oncology. Chicago, IL, USA, 1-5 June 2012 (Abstract CRA3503
14. Allegra CJ, Lakomy R, Tabernero J et al. Effects of prior bevacizumab (B) use on outcomes from the VELOUR study: a Phase III study of aflibercept (Afl) and FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin regimen. J. Clin. Oncol. 30(4 Suppl.), Abstract 3505 (2012)
15. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 473(7347), 298-307 (2011)
16. Mulder K, Koski S, Scarfe A, Chu Q, King K, Spratlin J. Antiangiogenic agents in advanced gastrointestinal malignancies: past, present and a novel future. Oncotarget 1(7), 515-529 (2010)
17. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. 25(4), 581-611 (2004)
18. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 92(6), 735-745 (1998)
19. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935), 1306-1309 (1989
20. Keck PJ, Hauser SD, Krivi G et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246(4935), 1309-1312 (1989
21. Ferrara N, Carver-Moore K, Chen H et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573), 439-442 (1996
22. Carmeliet P, Ferreira V, Breier G et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573), 435-439 (1996
23. Hilmi C, Guyot M, Pagès G. VEGF spliced variants: possible role of antiangiogenesis therapy. J. Nucleic Acids doi:10.1155/2012/162692 (2012) (Epub ahead of print
24. Olofsson B, Korpelainen E, Pepper MS et al. Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc. Natl Acad. Sci. USA 95(20), 11709-11714 (1998)
25. Aase K, von Euler G, Li X et al. Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect. Circulation 104(3), 358-364 (2001)
26. Li X, Lee C, Tang Z et al. VEGF-B: a survival, or an angiogenic factor? Cell. Adh. Migr. 3(4), 322-327 (2009)
27. Carmeliet P, Moons L, Luttun A et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat. Med. 7(5), 575-583 (2001)
28. Park JE, Chen HH, Winer J, Houck KA, Ferrara N. Placenta growth factor: potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J. Biol. Chem. 269(41), 25646-25654 (1994)
29. Wei SC, Tsao PN, Yu SC et al. Placenta growth factor expression is correlated with survival of patients with colorectal cancer. Gut 54(5), 666-672 (2005)
30. Fischer C, Jonckx B, Mazzone M et al. Anti-PlGF inhibits growth of VEGF(R)- inhibitor-resistant tumors without affecting healthy vessels. Cell 131(3), 463-475 (2007)
31. Taylor AP, Osorio L, Craig R et al. Tumorspecific regulation of angiogenic growth factors and their receptors during recovery from cytotoxic therapy. Clin. Cancer Res. 8(4), 1213-1222 (2002)
32. Rini BI, Michaelson MD, Rosenberg JE et al. Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. J. Clin. Oncol. 26(22), 3743-3748 (2008)
33. Wolpin BM, Mayer RJ. Systemic treatment of colorectal cancer. Gastroenterology 134(5), 1296-1310 (2008)
34. Folkman J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285(21), 1182-1186 (1971
35. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307(5706), 58-62 (2005)
36. Park JW, Kerbel RS, Kelloff GJ et al. Rationale for biomarkers and surrogate end points in mechanism-driven oncology drug development. Clin. Cancer Res. 10(11), 3885-3896 (2004)
37. Kindler HL, Niedzwiecki D, Hollis D et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: Phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J. Clin. Oncol. 28(22), 3617-3622 (2010)
38. Papadopoulos N, Martin J, Ruan Q et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis 15(2), 171-185 (2012)
39. Holash J, Davis S, Papadopoulos N et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc. Natl Acad. Sci. USA 99(17), 11393-11398 (2002)
40. Kopetz S, Hoff PM, Morris JS et al. 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(3), 453-459 (2010)
41. Rudge JS, Holash J, Hylton D et al. VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc. Natl Acad. Sci. USA 104(47), 18363-18370 (2007)
42. Tew WP, Gordon M, Murren J et al. Phase I study of aflibercept administered subcutaneously to patients with advanced solid tumors. Clin. Cancer Res. 16(1), 358-366 (2010)
43. Saltz LB, Clarke S, Díaz-Rubio E et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized Phase III study. J. Clin. Oncol. 26(12), 2013-2019 (2008)
44. Tol J, Koopman M, Cats A et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N. Engl. J. Med. 360(6), 563-572 (2009). Erratum in: N. Engl. J. Med. 363(26), 2573 (2010)
45. Hecht JR, Mitchell E, Chidiac T et al. A randomized Phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J. Clin. Oncol. 27(5), 672-680 (2009)
46. Stathopoulos GP, Batziou C, Trafalis D et al. Treatment of colorectal cancer with and without bevacizumab: a Phase III study. Oncology 78(5-6), 376-381 (2010)
47. Tebbutt NC, Wilson K, Gebski VJ et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J. Clin. Oncol. 28(19), 3191-3198 (2010)
48. Fabbri F, Passardi A, Ravaioli A et al.; ITACa Study Group. Sequential treatment strategy for metastatic colorectal cancer: a Phase III study of chemotherapy (CT) with or without bevacizumab (Bev) as first-line therapy followed by two Phase III studies of CT alone or CT plus bev with or without cetuximab (Cetux) as second-line therapy (ITACa Study IRST 153 01). J. Clin. Oncol. 29(Suppl.), Abstract e14161 (2011)
49. Giantonio BJ, Catalano PJ, Meropol NJ et al. 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(12), 1539-1544 (2007)
50. Tabernero J, Van Cutsem E, Lakomy R et al. Results from VELOUR, a Phase III study of aflibercept (A) versus placebo (pbo) in combination with FOLFIRI for the treatment of patients (pt) with previously treated metastatic colorectal cancer (MCRC). Eur. J. Cancer 47(Suppl. 2), 5 Abstract 6LBA (2011)
51. Allegra CJ, Tabernero J, Rougier P et al. Meta-analysis of anti-VEGF class adverse events from three double-blind (Db) placebo (Pbo)-controlled Phase III trials with IV aflibercept (Afl). J. Clin. Oncol. 30(Suppl. 4), Abstract 561 (2012)
52. Kozloff M, Yood MU, Berlin J et al. Investigators of the BRiTE study. Clinical outcomes associated with bevacizumabcontaining treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist 14(9), 862-870 (2009)
53. Grothey A, Sugrue MM, Purdie DM et al. Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE). J. Clin. Oncol. 26(33), 5326-5334 (2008)
54. Van Cutsem E, Rivera F, Berry S et al. First BEAT investigators. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann. Oncol. 20(11), 1842-1847 (2009)
55. Okines A, Puerto OD, Cunningham D et al. Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomized Phase-III NO16966 trial. Br. J. Cancer 101(7), 1033-1038 (2009)
56. Cohn AL, Bekaii-Saab T, Bendell JC et al.; ARIES Study Investigators. Clinical outcomes in bevacizumab (BV)- treated patients (pts) with metastatic colorectal cancer (mCRC): results from ARIES observational cohort study (OCS) and confirmation of BRiTE data on BV beyond progression (BBP). J. Clin. Oncol. 28(15 Suppl.), Abstract 3596 (2010)
57. Hurwitz H, Douglas P, Middleton J et al. Analysis of early hypertension (HTN) and clinical outcome with bevacizumab (BV). J. Clin. Oncol. 28(Suppl. 15), Abstract 3039 (2010)
58. Willett CG, Duda DG, di Tomaso E et al. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary Phase II study. J. Clin. Oncol. 27(18), 3020-3026 (2009)
59. Pohl M, Werner N, Munding J et al. Biomarkers of anti-angiogenic therapy in metastatic colorectal cancer (mCRC): original data and review of the literature. Z. Gastroenterol. 49(10), 1398-1406 (2011)
60. Jubb AM, Hurwitz HI, Bai W et al. Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J. Clin. Oncol. 24(2), 217-227 (2006)
61. Pectasides D, Papaxoinis G, Kalogeras K et al. XELIRI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group Phase III trial with collateral biomarker analysis. BMC Cancer 12(1), 271 (2012)
62. 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. 28(20), 3239-3247 (2010)
63. Van Cutsem E, Jayson G, Dive C et al. ORAL analysis of blood plasma factors in the AVITA Phase III randomized study of bevacizumab (bev) with gemcitabineerlotinib (GE) in patients (pts) with metastatic pancreatic cancer (mPC). Agr. Ecosyst. Environ. 47(Abstract 803), S95-S96 (2011)
64. Van Cutsem E, de Haas S, Kang YK et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized Phase III trial. J. Clin. Oncol. 30(17), 2119-2127 (2012)
65. Lieu CH, Tran HT, Jiang Z et al. The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer. J. Clin. Oncol. 29(Suppl.), Abstract 3533 (2011)
66. Weickhardt AJ, Williams D, Lee C et al. Vascular endothelial growth factors (VEGF) and VEGF receptor expression as predictive biomarkers for benefit with bevacizumab in metastatic colorectal cancer (mCRC): analysis of the Phase III MAX study. J. Clin. Oncol. 29(Suppl.), Abstract 3531 (2011)
67. Gerger A, El-Khoueiry A, Zhang W et al. Pharmacogenetic angiogenesis profiling for first-line bevacizumab plus oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Clin. Cancer Res. 17(17), 5783-5792 (2011)
68. Koutras AK, Antonacopoulou AG, Eleftheraki AG et al. Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab. Pharmacogenomics 16 12(6), 468-475 (2011)
69. Loupakis F, Ruzzo A, Salvatore L et al. Retrospective exploratory analysis of VEGF polymorphisms in the prediction of benefit from first-line FOLFIRI plus bevacizumab in metastatic colorectal cancer. BMC Cancer 11
70. Lambrechts D, Claes B, Delmar P et al. VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol. 13(7), 724-733 (2012)
71. National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Colon cancer (Version 3) (2012). www.nccn.org/professionals/physician- gls/pdf/colon.pdf