Abstract
Introducing the monoclonal vascular endothelial growth factor (VEGF) antibody bevacizumab to first-line treatment was the first implementation of a targeted therapy for ovarian cancer patients. Until then, standard of care for more than 10 years had been the combination chemotherapy of six cycles of carboplatin and paclitaxel every 3 weeks. Two phase III trials on bevacizumab proved efficacy of anti-angiogenic therapy for first-line setting in 2011 leading to approval in several countries. Since then, bevacizumab has become available for different therapeutic indications although the treatment effect is still restricted to progression-free survival in the target groups. Therefore, further tailored treatment strategies have been studied or are still under investigation to improve efficacy and possibly reduce toxicity. Combinations of anti-angiogenic therapies with other effective drugs to overcome resistance are further promising approaches being currently tested in clinical trials.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Aghajanian C, Sill MW et al (2011) Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol 29(16):2259–2265
Aghajanian C, Blank SV et al (2012) 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 30(17):2039–2045
Aghajanian C, Goff B et al (2015) Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol 139(1):10–16
Baumann KH, du Bois A et al (2012) A phase II trial (AGO 2.11) in platinum-resistant ovarian cancer: a randomized multicenter trial with sunitinib (SU11248) to evaluate dosage, schedule, tolerability, toxicity and effectiveness of a multitargeted receptor tyrosine kinase inhibitor monotherapy. Ann Oncol 23(9):2265–2271
Biagi JJ, Oza AM et al (2011) A phase II study of sunitinib in patients with recurrent epithelial ovarian and primary peritoneal carcinoma: an NCIC Clinical Trials Group Study. Ann Oncol 22(2):335–340
Burger RA, Brady MF et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365(26):2473–2483
du Bois A, Luck HJ et al (2003) A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 95(17):1320–1329
du Bois A, Floquet A et al (2014) Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol 32(30):3374–3382
du Bois A, Kristensen G et al (2016) Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 17(1):78–89
De Felice F, Marchetti C et al (2015) Immunotherapy of ovarian cancer: the role of checkpoint inhibitors. J Immunol Res 2015:191832
Friedlander M, Hancock KC et al (2010) A phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol 119(1):32–37
Graybill W, Sood AK et al (2015) State of the science: emerging therapeutic strategies for targeting angiogenesis in ovarian cancer. Gynecol Oncol 138(2):223–226
Herzog TJ, Scambia G et al (2013) A randomized phase II trial of maintenance therapy with Sorafenib in front-line ovarian carcinoma. Gynecol Oncol 130(1):25–30
Karlan BY, Oza AM et al (2012) Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer. J Clin Oncol 30(4):362–371
Kim JW, Mahner S et al (2015) Pazopanib maintenance therapy in East Asian women with advanced epithelial ovarian cancer: results from AGO-OVAR16 and an East Asian study. Int J Gynecol Cancer 25:279–287
Kusmartsev S, Eruslanov E et al (2008) Oxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma. J Immunol 181(1):346–353
Ledermann JA, Hackshaw A et al (2011) Randomized phase II placebo-controlled trial of maintenance therapy using the oral triple angiokinase inhibitor BIBF 1120 after chemotherapy for relapsed ovarian cancer. J Clin Oncol 29(28):3798–3804
Ledermann JA, Embleton AC et al (2016) Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 387(10023):1066–1074
Liu JF, Barry WT et al (2014) Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol 15(11):1207–1214
Mahner S, Eulenburg C et al (2013) Prognostic impact of the time interval between surgery and chemotherapy in advanced ovarian cancer: analysis of prospective randomised phase III trials. Eur J Cancer 49(1):142–149
Matei D, Sill MW et al (2011) Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: a gynecologic oncology group trial. J Clin Oncol 29(1):69–75
Matulonis UA, Berlin S et al (2009) Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol 27(33):5601–5606
McCormack PL (2015) Nintedanib: first global approval. Drugs 75(1):129–139
Mendel DB, Laird AD et al (2003) In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 9(1):327–337
Monk BJ, Choi DC et al (2005) Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian cancer. Gynecol Oncol 96(3):902–905
Monk BJ, Poveda A et al (2014) Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol 15(8):799–808
Monk BJ, Poveda A et al (2015) 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 33(15_suppl (abstr 5552))
Monk BJ, Minion LE et al (2016) Anti-angiogenic agents in ovarian cancer: past, present, and future. Ann Oncol 27(Suppl 1):i33–i39
Oza AM, Cook AD et al (2015) 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 16(8):928–936
Ozols RF, Bundy BN et al (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 21(17):3194–3200
Perren TJ, Swart AM et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365(26):2484–2496
Pignata S, Lorusso D et al (2015) Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol 16(5):561–568
Poveda AM, Selle F et al (2015) Bevacizumab combined with weekly paclitaxel, Pegylated liposomal doxorubicin, or Topotecan in platinum-resistant recurrent ovarian cancer: analysis by chemotherapy cohort of the randomized phase III AURELIA trial. J Clin Oncol 33(32):3836–3838
Pujade-Lauraine E, Hilpert F et al (2012) AURELIA: a randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC). J Clin Oncol 30s, abstr LBA5002
Raja FA, Griffin CL et al (2011) Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer. Br J Cancer 105(7):884–889
Sehouli J, Hilpert F et al (2016) Topotecan (T) ± sorafenib (S) in platinum-resistant ovarian cancer (PROC): a double-blind placebo-controlled randomized NOGGO–AGO intergroup Trial – TRIAS. J Clin Oncol 34 (suppl; abstr 5522)
Trillsch F, Mahner S et al (2016) Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial. Ann Oncol 27(9):1733–1739
Wilhelm S, Carter C et al (2006) Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 5(10):835–844
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this entry
Cite this entry
Mahner, S., Trillsch, F. (2019). The Value of Anti-angiogenics in Ovarian Cancer Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-33673-2_25
Download citation
DOI: https://doi.org/10.1007/978-3-319-33673-2_25
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-33671-8
Online ISBN: 978-3-319-33673-2
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences