Bevacizumab in ovarian cancer: Focus on clinical data and future perspectives

Critical Reviews in Oncology/Hematology

Volumn 97, Issue , 2016, Pages 335-348

  Colombo, Nicoletta ^a   Conte, Pier Franco ^b   Pignata, Sandro ^c   Raspagliesi, Francesco ^d   Scambia, Giovanni ^e  

^a EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

^b UNIVERSITY OF PADOVA   (Italy)

^c NATIONAL CANCER INSTITUTE   (Italy)

^d NATIONAL CANCER INSTITUTE   (Italy)

^e FONDAZIONE POLICLINICO UNIVERSITARIO A GEMELLI IRCCS   (Italy)

Author keywords

Anti angiogenic; Bevacizumab; Front line; Ovarian cancer; Phase III; Vascular endothelial growth factor

Indexed keywords

ANGIOGENESIS INHIBITOR; BEVACIZUMAB; CARBOPLATIN; PACLITAXEL; PLACEBO; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY;

CANCER GROWTH; CANCER RECURRENCE; CANCER STAGING; CANCER SURVIVAL; CLINICAL EVALUATION; DIGESTIVE SYSTEM PERFORATION; DRUG EFFECT; DRUG EFFICACY; DRUG INDICATION; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; MULTIPLE CYCLE TREATMENT; NONHUMAN; OUTCOME ASSESSMENT; OVARY CANCER; OVERALL SURVIVAL; PATIENT SELECTION; PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; TREATMENT DURATION; FEMALE; OVARIAN NEOPLASMS;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; BEVACIZUMAB; CLINICAL TRIALS, PHASE III AS TOPIC; FEMALE; HUMANS; OVARIAN NEOPLASMS;

EID: 84952638192     PISSN: 10408428     EISSN: 18790461     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2015.08.017     Document Type: Review

References (96)

1. Aghajanian C., Blank S.V., Goff B.A., Judson P.L., Teneriello M.G., Husain A., et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J. Clin. Oncol. 2012, 30:2039-2045.
2. Aghajanian C., Nycum L.R., Goff B., Nguyen H., Husain A., Blank S.V. Updated overall survival analysis in OCEANS, a randomized phase 3 trial of gemcitabine (G)+carboplatin (C) and bevacizumab (BV) or placebo (PL) followed by BV or PL in platinum-sensitive recurrent epithelial ovarian (ROC), primary peritoneal (PPC), or fallopian tube cancer (FT). Ann. Oncol. 2012, 23(Suppl. 9). ix319-33 (abstract 967O).
3. Aghajanian C., Goff B., Nycum L.R., Wang Y., Husain A., Blank S. Independent radiologic review: bevacizumab in combination with gemcitabine and carboplatin in recurrent ovarian cancer. Gynecol. Oncol. 2014, 133:105-110.
4. Aghajanian C., Goff B., Nycum L.R., Wang Y., Husain A., Blank S.V. Final analysis of overall survival in OCEANS, a randomized phase III trial of gemcitabine, carboplatin, and bevacizumab followed by bevacizumab until disease progression in patients with platinum-sensitive recurrent ovarian cancer. Society of Gynecologic Oncology Annual Meeting 2014, (abstract 137).
5. Alitalo K., Tammela T., Petrova T.V. Lymphangiogenesis in development and human disease. Nature 2005, 438:946-953.
6. Armstrong, D.K., Bundy, B.,Wenzel, L., Huang, H.Q., Baergen, R., Lele, S., et al.; Gynecologic Oncology Group, 2006. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N. Engl. J. Med. 354, 34-43.
7. Backen A., Renehan A., Clamp A., Berzuini C., Zhou C., Oza A., et al. The combination of circulating Ang1 and Tie2 levels predict progression free survival advantage in bevacizumab-treated ovarian cancer patients. Clin. Cancer Res. 2014, 20:4549-4558.
8. Bagri A., Berry L., Gunter B., Singh M., Kasman I., Damico L.A., et al. Effects of anti-VEGF treatment duration on tumor growth, tumor regrowth, and treatment efficacy. Clin. Cancer Res. 2010, 16:3887-3900.
9. Banerjee S., Kaye S. The role of targeted therapy in ovarian cancer. Eur. J. Cancer 2011, 47(Suppl. 3):S116-S130.
10. Bennouna, J., Sastre, J., Arnold, D., Österlund, P., Greil, R., Van Cutsem, E., et al.; ML18147 Study Investigators, 2013. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 14, 29-37.
11. Birrer M., Lankes H., Burger R.A., Mannel R., Homesley H., Sovak M., et al. Biomarker (BM) results from GOG-0218, a phase 3 trial of front-line bevacizumab (BV)+chemotherapy (CT) for ovarian cancer (OC). ESMO 2012, (poster 198P).
12. Birrer M.J., Choi Y.J., Brady M.F., Mannel R.S., Burger R.A., Wei W., et al. Retrospective analysis of candidate predictive tumor biomarkers (BMs) for efficacy in the GOG-0218 trial evaluating front-line carboplatin-paclitaxel (CP)±bevacizumab (BEV) for epithelial ovarian cancer (EOC). J. Clin. Oncol. 2015, 33(Suppl). abstract 5505.
13. Bolis G., Scarfone G., Raspagliesi F., Mangili G., Danese S., Scollo P., et al. Paclitaxel/carboplatin versus topotecan/paclitaxel/carboplatin in patients with FIGO suboptimally resected stage III-IV epithelial ovarian cancer: a multicenter, randomized study. Eur. J. Cancer 2010, 46:2905-2912.
14. Broglio K.R., Berry D.A. Detecting an overall survival benefit that is derived from progression-free survival. J. Natl. Cancer Inst. 2009, 101:1642-1649.
15. Burger R.A., Sill M.W., Monk B.J., Greer B.E., Sorosky J.I. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J. Clin. Oncol. 2007, 25:5165-5171.
16. Burger, R.A., Brady, M.F., Bookman, M.A., Fleming, G.F., Monk, B.J., Huang, H., et al.; Gynecologic Oncology Group, 2011. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N. Engl. J. Med. 365, 2473-2483.
17. Burger R.A., Brady M.F., Rhee J., Sovak M.A., Kong G., Nguyen H.P., Bookman M.A. Independent radiologic review of the Group Study 0218, a phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. Gynecol. Oncol. 2013, 131:21-26.
18. Burger R.A., Brady M.F., Bookman M.A., Monk B.J., Walker J.L., Homesley H.D., et al. Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: a Gynecologic Oncology Group Study. J. Clin. Oncol. 2014, 32:1210-1217.
19. Byrne A.T., Ross L., Holash J., Nakanishi M., Hu L., Hofmann J.I., et al. Vascular endothelial growth factor-trap decreases tumor burden, inhibits ascites, and causes dramatic vascular remodeling in an ovarian cancer model. Clin. Cancer Res. 2003, 9:5721-5728.
20. Cameron D., Brown J., Dent R., Jackisch C., Mackey J., Pivot X., et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial. Lancet Oncol. 2013, 14:933-942.
21. Cannistra S.A., Matulonis U.A., Penson R.T., Hambleton J., Dupont J., Mackey H., et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J. Clin. Oncol. 2007, 25:5180-5186.
22. Carmeliet P., Ferreira V., Breier G., Pollefeyt S., Kieckens L., Gertsenstein M., et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996, 380:435-439.
23. Chan J., Brady M., Penson R., Monk B., Boente M., Walker J., et al. Phase III trial of every-3-weeks paclitaxel vs. dose dense weekly paclitaxel with carboplatin +/- bevacizumab in epithelial ovarian, peritoneal, fallopian tube cancer: GOG 262 (NCT01167712). Int. J. Gynecol. Cancer 2013, 23(8 Suppl. 1):9. (plenary session abstract).
24. Chung A.S., Lee J., Ferrara N. Targeting the tumour vasculature: insights from physiological angiogenesis. Nat. Rev. Cancer 2010, 10:505-514.
25. Coleman R.L., Brady M.F., Herzog T.J., Sabbatini P., Armstrong D.K., Walker J.L., et al. A phase III randomized controlled clinical trial of carboplatin and paclitaxel alone or in combination with bevacizumab followed by bevacizumab and secondary cytoreductive surgery in platinum-sensitive, recurrent ovarian, peritoneal primary and fallopian tube cancer (Gynecologic Oncology Group 213). Society of Gynecologic Oncology's Annual Meeting on Women's Cancer 2015, Abstract 3 (late breaking).
26. Colombo N., Selle F., Korach J., Mendiola C., Davidenko I., Joly F., et al. Assessment of safety of surgery in patients with ovarian cancer treated with carboplatin/paclitaxel/bevacizumab in the ROSiA routine oncology practice study. Int. J. Gynecol. Cancer 2013, 23(8 Suppl. 1):128.
27. du Bois, A., Weber, B., Rochon, J., Meier, W., Goupil, A., Olbricht, S., et al.; Arbeitsgemeinschaft Gynaekologische Onkologie; Ovarian Cancer Study Group; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens, 2006. Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens. J. Clin. Oncol. 24, 1127-1135.
28. du Bois A., Herrstedt J., Hardy-Bessard A.C., Mueller H.-H., Harter P., Kristensen G., et al. Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in firstline treatment of epithelial ovarian cancer. J. Clin. Oncol. 2010, 28:4162-4169.
29. du Bois A., Kristensen G., Ray-Coquard I., Reuss A., Pignata S., Colombo N., et al. AGO-OVAR 12: a randomized placebo-controlled GCIG/ENGOT-Intergroup phase III trial of standard frontline chemotherapy +/- nintedanib for advanced ovarian cancer. Int. J. Gynecol. Cancer 2013, 23(8 Suppl. 1):7.
30. du Bois A., Floquet A., Kim J.W., Rau J., del Campo J.M., Friedlander M., et al. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J. Clin. Oncol. 2014, 32:3374-3382.
31. De Placido S., Scambia G., Di Vagno G., Naglieri E., Lombardi A.V., Biamonte R., et al. Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study. J. Clin. Oncol. 2004, 22:2635-2642.
32. Ellis L.M., Haller D.G. Bevacizumab beyond progression: does this make sense?. J. Clin. Oncol. 2008, 26:5313-5315.
33. Ferrara N., Carver-Moore K., Chen H., Dowd M., Lu L., O'Shea K.S., et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996, 380:439-442.
34. Ferrara N., Chen H., Davis-Smyth T., Gerber H.-P., Nguyen T.-N., Peers D., et al. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat. Med. 1998, 4:336-340.
35. Ferrara N., Gerber H.P., LeCouter J. The biology of VEGF and its receptors. Nat. Med. 2003, 9:669-676.
36. Ferrara N., Frantz G., LeCouter J., Dillard-Telm L., Pham T., Draksharapu A., et al. Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. Am. J. Pathol. 2003, 162:1881-1893.
37. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. 2004, 25:581-611.
38. Fraser H.M., Lunn S.F. Angiogenesis and its control in the female reproductive system. Br. Med. Bull. 2000, 56:787-797.
39. Fraser H.M., Dickson S.E., Lunn S.F., Wulff C., Morris K.D., Carroll V.A., et al. Suppression of luteal angiogenesis in the primate after neutralization of vascular endothelial growth factor. Endocrinology 2000, 141:995-1000.
40. Fujita K., Sano D., Kimura M., Yamashita Y., Kawakami M., Ishiguro Y., et al. Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck squamous cell carcinoma. Oncol. Rep. 2007, 18:47-51.
41. Gadducci A., Carnino F., Chiara S., Brunetti I., Tanganelli L., Romanini A., et al. Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer: a randomized trial of the Gruppo Oncologico Nord-Ovest. Gynecol. Oncol. 2000, 76(2):157-162.
42. García Y., De Juan A., Mendiola C., Barretina-Ginesta P., Vidal L., Santaballa A., et al. Phase II randomized trial of neoadjuvant (NA) chemotherapy (CT) with or without bevacizumab (Bev) in advanced epithelial ovarian cancer (EOC) (GEICO 1205/NOVA TRIAL). J. Clin. Oncol. 2015, 33(Suppl). abstract 5531.
43. Gerber H.P., Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005, 65:671-680.
44. Giantonio B.J. Targeted therapies: Goldie-Coldman and bevacizumab beyond disease progression. Nat. Rev. Clin. Oncol. 2009, 6:311-312.
45. Gonzalez-Martin A., Gladieff L., Tholander B., Stroyakovsky D., Gore M., Scambia G., et al. Efficacy and safety results from OCTAVIA, a single-arm phase II study evaluating front-line bevacizumab, carboplatin and weekly paclitaxel for ovarian cancer. Eur. J. Cancer 2013, 49:3831-3838.
46. Gonzalez-Martin A., Gladieff L., Tholander B., Stroyakovsky D., Gore M., Scambia G., et al. Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer). Eur. J. Cancer 2014, 50:862-863.
47. Gourley C., McCavigan A., Perren T., Paul J., Ogilvie Michie C., Churchman M., et al. Molecular subgroup of high-grade serous ovarian cancer (HGSOC) as a predictor of outcome following bevacizumab. J. Clin. Oncol. 2014, 32(Suppl). 5s (abstract 5502).
48. Gridelli C., Bennouna J., de Castro J., Dingemans A.M., Griesinger F., Grossi F., et al. Randomized phase IIIb trial evaluating the continuation of bevacizumab beyond disease progression in patients with advanced non-squamous non-small-cell lung cancer after first-line treatment with bevacizumab plus platinum-based chemotherapy: treatment rationale and protocol dynamics of the AvaALL (MO22097) trial. Clin. Lung Cancer 2011, 12:407-411.
49. Hu L., Hofmann J., Zaloudek C., Ferrara N., Hamilton T., Jaffe R.B. Vascular endothelial growth factor immunoneutralization plus paclitaxel markedly reduces tumor burden and ascites in athymic mouse model of ovarian cancer. Am. J. Pathol. 2002, 161:1917-1924.
50. Jain R.K. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005, 307:58-62.
51. Karkkainen M.J., Makinen T., Alitalo K. Lymphatic endothelium: a new frontier of metastasis research. Nat. Cell Biol. 2002, 4:E2-E5.
52. Katsumata N., Yasuda M., Takahashi F., Isonishi S., Jobo T., Aoki D., et al. Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet 2009, 374:1331-1338.
53. Katsumata N., Yasuda M., Isonishi S., Takahashi F., Michimae H., Kimura E., et al. Japanese Gynecologic Oncology Group. Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Lancet Oncol. 2013, 14:1020-1026.
54. Kim K.J., Li B., Winer J., Armanini M., Gillett N., Phillips H.S., Ferrara N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 1993, 362:841-844.
55. Klement G., Baruchel S., Rak J., Man S., Clark K., Hicklin D.J., et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J. Clin. Invest. 2000, 105:R15-R24.
56. Kowanetz M., Ferrara N. Vascular endothelial growth factor signalling pathways: therapeutic perspective. Clin. Cancer Res. 2006, 12:5018-5022.
57. Ledermann J.A., Marth C., Carey M.S., Birrer M., Bowtell D.D., Kaye S., et al. Gynecologic Cancer InterGroup. Role of molecular agents and targeted therapy in clinical trials for women with ovarian cancer. Int. J. Gynecol. Cancer 2011, 21:763-770.
58. Ledermann J.A., Perren T.J., Raja F.A., Embleton A.C., Rustin G.J.S., Jayson G., et al. Randomised double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum sensitive ovarian cancer: results of the ICON6 trial. Eur. Cancer Congress 2013, (abstract LBA10).
59. Leung D.W., Cachianes G., Kuang W.J., Goeddel D.V., Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989, 246:1306-1309.
60. Li L., Wang L., Zhang W., Tang B., Zhang J., Song H., et al. Correlation of serum VEGF levels with clinical stage, therapy efficacy, tumor metastasis and patient survival in ovarian cancer. Anticancer Res. 2004, 24(3b):1973-1979.
61. Liu J.F., Barry W.T., Birrer M., Lee J.M., Buckanovich R.J., Fleming G.F., et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014, 15:1207-1214.
62. Mabuchi S., Terai Y., Morishige K., Tanabe-Kimura A., Sasaki H., Kanemura M., et al. Maintenance treatment with bevacizumab prolongs survival in an in vivo ovarian cancer model. Clin. Cancer Res. 2008, 14:7781-7789.
63. Mancuso M.R., Davis R., Norberg S.M., O'Brien S., Sennino B., Nakahara T., et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J. Clin. Invest. 2006, 116:2610-2621.
64. Mendiola C., Davidenko I., Colombo N., Korach J., Selle F., Gocze P., et al. ROSiA: a single-arm study in more than 1000 patients (pts) receiving front-line bevacizumab (BEV)+chemotherapy (CT) for ovarian cancer (OC). Ann. Oncol. 2012, 23(Suppl. 9). ix322(abstract 978P).
65. Mesiano S., Ferrara N., Jaffe R.B. Role of vascular endothelial growth factor in ovarian cancer: inhibition of ascites formation by immunoneutralization. Am. J. Pathol. 1998, 153:1249-1256.
66. Miles D.W., de Haas S.L., Dirix L.Y., Romieu G., Chan A., Pivot X., 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, 108:1052-1060.
67. Monk B.J., Huang H.Q., Burger R.A., Mannel R.S., Homesley H.D., Fowler F., et al. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol. Oncol. 2013, 128:573-578.
68. Monk B.J., Poveda A., Vergote I., Raspagliesi F., Fujiwara K., Bae D.-S., et al. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014, 15:799-808.
69. Monk B.J., Poveda A., Vergote I., Raspagliesi F., Fujiwara K., Bae D.-S., et al. Impact of trebananib plus weekly paclitaxel on overall survival (OS) in patients (pts) with recurrent ovarian cancer and ascites: Results from the phase III TRINOVA-1 study. J. Clin. Oncol. 2015, 33(Suppl). abstract 5503.
70. Neufeld G., Cohen T., Shraga N., Lange T., Kessler O., Herzog Y. The neuropilins: multifunctional semaphorin and VEGF receptors that modulate axon guidance and angiogenesis. Trends Cardiovasc. Med. 2002, 12:13-19.
71. Oza A.M., Cook A.D., Pfisterer J., Embleton A., Ledermann J.A., Pujade-Lauraine E., et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015, 16:928-936.
72. Pajusola K., Aprelikova O., Korhonen J., Kaipainen A., Pertovaara L., Alitalo R., et al. FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. Cancer Res. 1992, 52:5738-5743.
73. Perren, T.J., Swart, A.M., Pfisterer, J., Ledermann, J.A., Pujade-Lauraine, E., Kristensen, G., et al.; ICON7 Investigators, 2011. A phase 3 trial of bevacizumab in ovarian cancer. N. Engl. J Med. 365, 2484-2496.
74. Pfisterer J., Weber B., Reuss A., Kimmig R., du Bois A., Wagner U., et al. AGO-OVAR; GINECO. Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO. J. Natl. Cancer Inst. 2006, 98:1036-1045.
75. Phillips H.S., Hains J., Leung D.W., Ferrara N. Vascular endothelial growth factor is expressed in rat corpus luteum. Endocrinology 1990, 127:965-967.
76. Pujade-Lauraine E., Hilpert F., Weber B., Reuss A., Poveda A., Kristensen G., et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J. Clin. Oncol. 2014, 32:1302-1308.
77. Randall L., Burger R., Nguyen H., Kong G., Bookman M., Fleming G., et al. Outcome differences in patients with advanced epithelial ovarian, primary peritoneal and fallopian tube cancers treated with and without bevacizumab. Gynecol. Oncol. 2013, 130:e33. (abstract 80).
78. Roche. Avastin Summary of Product Characteristics, 2014a. (accessed 29.12.14.). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000582/WC500029271.pdf.
79. Roche. Avastin Prescribing Information 2014b. (accessed 29.12.14.). http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125085s225lbl.pdf.
80. Rouzier R., Morice P., Floquet A., Selle F., Lambaudie E., Fourchotte V., et al. A randomized, open-label, phase II study assessing the efficacy and the safety of bevacizumab in neoadjuvant therapy in patients with FIGO stage IIIc/IV ovarian, tubal, or peritoneal adenocarcinoma, initially unresectable. J. Clin. Oncol. 2014, 32(Suppl). 5s (abstract TPS5614).
81. Rowe D.H., Huang J., Kayton M.L., Thompson R., Troxel A., O'Toole K.M., et al. Anti-VEGF antibody suppresses primary tumor growth and metastasis in an experimental model of Wilms' tumor. J. Pediatr. Surg. 2000, 35:30-32.
82. Ryan A.M., Eppler D.B., Hagler K.E., Bruner R.H., Thomford P.J., Hall R.L., et al. Preclinical safety evaluation of rhuMAbVEGF, an antiangiogenic humanized monoclonal antibody. Toxicol. Pathol. 1999, 27:78-86.
83. Shibuya M. Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): a dual regulator for angiogenesis. Angiogenesis 2006, 9(4):225-230.
84. Singh M., Ferrara N. Modeling and predicting clinical efficacy for drugs targeting the tumor milieu. Nat. Biotechnol. 2012, 30:648-657.
85. Smerdel M.P., Steffensen K.D., Waldstrøm M., Brandslund I., Jakobsen A. The predictive value of serum VEGF in multiresistant ovarian cancer patients treated with bevacizumab. Gynecol. Oncol. 2010, 118:167-171.
86. Stark D., Nankivell M., Pujade-Lauraine E., Kristensen G., Elit L., Stockler M., et al. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol. 2013, 14:236-243.
87. Stockler M.R., Hilpert F., Friedlander M., King M.T., Wenzel L., Lee C.K., et al. Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer. J. Clin. Oncol. 2014, 32:1309-1316.
88. Thigpen T., du Bois A., McAlpine J., DiSaia P., Fujiwara K., Hoskins W., et al. First-line therapy in ovarian cancer trials. Int. J. Gynecol. Cancer 2011, 21:756-762.
89. Van Cutsem E., Jayson G., Dive C., Dilba P., de Haas S., Wild N., et al. Diagnostic/biomarkers: personalized medicine. Analysis of blood plasma factors in the AVITA phase III randomized study of bevacizumab (bev) with gemcitabine-erlotinib (GE) in patients (pts) with metastatic pancreatic cancer (mPC). EMCC 2011, (abstract 803).
90. Van Cutsem E., de Haas S., Kang Y.K., Ohtsu A., Tebbutt N.C., Ming Xu J., 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. 2012, 30:2119-2127.
91. Vasey P.A., Jayson G.C., Gordon A., Gabra H., Coleman R., Atkinson R., et al. Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J. Natl. Cancer Inst. 2004, 96:1682-1691.
92. Vergote I., Tropé C.G., Amant F., Kristensen G.B., Ehlen T., Johnson N., et al. European Organization for Research and Treatment of Cancer-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N. Engl. J. Med. 2010, 363:943-953.
93. von Minckwitz G., Puglisi F., Cortes J., Vrdoljak E., Marschner N., Zielinski C., et al. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial. Lancet Oncol. 2014, 15:1269-1278.
94. Warren R.S., Yuan H., Matli M.R., Gillett N.A., Ferrara N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J. Clin. Invest. 1995, 95:1789-1797.
95. Winterhoff B.J.N., Kommoss S., Oberg A.L., Wang C., Riska S.M., Konecny G.E., et al. Bevacizumab and improvement of progression-free survival (PFS) for patients with the mesenchymal molecular subtype of ovarian cancer. J. Clin. Oncol. 2014, 32(Suppl):5s. (abstract 5509).
96. Yamamoto S., Konishi I., Mandai M., Kuroda H., Komatsu T., Nanbu K., et al. Expression of vascular endothelial growth factor (VEGF) in epithelial ovarian neoplasms: correlation with clinicopathology and patient survival, and analysis of serum VEGF levels. Br. J. Cancer 1997, 76:12217.