Drug Evaluation

Clinical Instructor, Department of Obstetrics & Gynecology, Research Fellow, Division of Gynecologic Oncology, University of California, 333 City Blvd West, Suite 1400, Orange, CA 92868, USA

*Author for correspondence: Tel.: +1 714 456 8020; Fax: +1 714 456 6632;

E-mail Address: ktewari@uci.edu

Professor & Division Director, Director, Division of Gynecologic Oncology, University of California, 333 City Blvd, Orange, CA 92868, USA

Department of Obstetrics & Gynecology, University of California, The City Tower, 333 City Blvd, West – Suite 1400, Orange, CA 92868, USA

Search for more papers by this author

Published Online:20 Nov 2019https://doi.org/10.2217/fon-2019-0042

View article

Abstract

On 13 June 2018, Genentech, Inc. issued a press release announcing that the US FDA had approved the antiangiogenesis drug, bevacizumab, in combination with chemotherapy for frontline and maintenance therapy for women with newly diagnosed ovarian cancer. Regulatory approval was based on the National Cancer Institute-sponsored Gynecologic Oncology Group (GOG) protocol 0218, the Phase III, randomized, placebo-controlled, double-blind, multi-center and multi-national clinical trial that met its primary end point, progression-free survival. Bevacizumab is now approved in the frontline, platinum-sensitive recurrent and platinum-resistant recurrent settings for epithelial ovarian cancer. This review will address the broad range of clinical trials addressing the efficacy of bevacizumab use in ovarian cancer.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Chen H, Ye D, Xie X, Chen B, Lu W. VEGF, VEGFRs expressions and activated STATs in ovarian epithelial carcinoma. Gynecol. Oncol. 94(3), 630–635 (2004).
Medline CASGoogle Scholar
2. Ozols RF, Bundy BN, Greer BE et al. 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 (2003).
Medline CASGoogle Scholar
3. Wild R, Dings RP, Subramanian I, Ramakrishnan S. Carboplatin selectively induces the VEGF stress response in endothelial cells: potentiation of antitumor activity by combination treatment with antibody to VEGF. Int. J. Cancer 110(3), 343–351 (2004).
Medline CASGoogle Scholar
4. Chan JK, Brady MF, Penson RT et al. Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer. N. Engl. J. Med. 374(8), 738–748 (2016).
Medline CASGoogle Scholar
5. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a gynecologic oncology group study. J. Clin. Oncol. 25(33), 5165–5171 (2007).
Medline CASGoogle Scholar
6. Cannistra SA, Matulonis UA, Penson RT et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J. Clin. Oncol. 25(33), 5180–5186 (2007).
Medline CASGoogle Scholar
7. Garcia AA, Hirte H, Fleming G et al. Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital Phase II Consortia. J. Clin. Oncol. 26(1), 76–82 (2008).
Medline CASGoogle Scholar
8. Burger RA, Brady MF, Bookman MA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N. Engl. J. Med. 365(26), 2473–2483 (2011). •• Published Phase III clinical trials reviewed in this paper.
Medline CASGoogle Scholar
9. Perren TJ, Swart AM, Pfisterer J et al. A Phase 3 trial of bevacizumab in ovarian cancer. N. Engl. J. Med. 365(26), 2484–2496 (2011). •• Published Phase III clinical trials reviewed in this paper.
Medline CASGoogle Scholar
10. Pujade-Lauraine E, Hilpert F, Weber B et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized Phase III trial. J. Clin. Oncol. 32(13), 1302–1308 (2014). •• Published Phase III clinical trials reviewed in this paper.
Medline CASGoogle Scholar
11. Aghajanian C, Blank SV, Goff BA 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. 30(17), 2039–2045 (2012). •• Published Phase III clinical trials reviewed in this paper.
Medline CASGoogle Scholar
12. Coleman RL, Brady MF, Herzog TJ et al. Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, Phase 3 trial. Lancet Oncol. 18(6), 779–791 (2017). •• Published Phase III clinical trials reviewed in this paper.
Medline CASGoogle Scholar
13. Burger RA, Brady MF, Rhee J et al. Independent radiologic review of the Gynecologic Oncology 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. 131(1), 21–26 (2013).
Medline CASGoogle Scholar
14. Burger RA, Enserro D, Tewari KS et al. Final overall survival (OS) analysis of an international randomized trial evaluating bevacizumab (BEV) in the primary treatment of advanced ovarian cancer: a NRG oncology/Gynecologic Oncology Group (GOG) study. J. Clin. Oncol. 36(15 Suppl.), 5517–5517 (2018).
Google Scholar
15. Oza AM, Cook AD, Pfisterer J 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. 16(8), 928–936 (2015).
Medline CASGoogle Scholar
16. Ruan G, Ye L, Liu G, An J, Sehouli J, Sun P. The role of bevacizumab in targeted vascular endothelial growth factor therapy for epithelial ovarian cancer: an updated systematic review and meta-analysis. Onco Targets Ther. 11, 521–528 (2018).
MedlineGoogle Scholar
17. Zhou M, Yu P, Qu X, Liu Y, Zhang J. Phase III trials of standard chemotherapy with or without bevacizumab for ovarian cancer: a meta-analysis. PLoS ONE 8(12), e81858 (2013). • This meta-analysis forms the basis of Table 2.
MedlineGoogle Scholar
18. Oza AM, Selle F, Davidenko I et al. Efficacy and safety of bevacizumab-containing therapy in newly diagnosed ovarian cancer: ROSiA single-arm Phase 3B study. Int. J. Gynecol. Cancer 27(1), 50–58 (2017).
MedlineGoogle Scholar
19. Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. 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 (2015).
Medline CASGoogle Scholar
20. Richardson DL, Backes FJ, Hurt JD et al. Which factors predict bowel complications in patients with recurrent epithelial ovarian cancer being treated with bevacizumab? Gynecol. Oncol. 118(1), 47–51 (2010).
Medline CASGoogle Scholar
21. Burger RA, Brady MF, Bookman MA 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. 32(12), 1210–1217 (2014).
Medline CASGoogle Scholar
22. Diaz JP, Tew WP, Zivanovic O et al. Incidence and management of bevacizumab-associated gastrointestinal perforations in patients with recurrent ovarian carcinoma. Gynecol. Oncol. 116(3), 335–339 (2010).
Medline CASGoogle Scholar
23. Vergote I, Tropé CG, Amant F et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N. Engl. J. Med. 363(10), 943–953 (2010).
Medline CASGoogle Scholar
24. Rouzier R, Gouy S, Selle F et al. Efficacy and safety of bevacizumab-containing neoadjuvant therapy followed by interval debulking surgery in advanced ovarian cancer: results from the ANTHALYA trial. Eur. J. Cancer 70, 133–142 (2017).
Medline CASGoogle Scholar
25. Tanyi JL, McCann G, Hagemann AR et al. Clinical predictors of bevacizumab-associated gastrointestinal perforation. Gynecol. Oncol. 120(3), 464–469 (2011).
Medline CASGoogle Scholar
26. Martin JY, Urban RR, Liao JB, Goff BA. Bevacizumab toxicity in heavily pretreated recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers. J. Gynecol. Oncol. 27(5), e47 (2016).
MedlineGoogle Scholar
27. Monk BJ, Huang HQ, Burger RA 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. 128(3), 573–578 (2013).
Medline CASGoogle Scholar
28. Petrillo M, Paris I, Vizzielli G et al. Neoadjuvant chemotherapy followed by maintenance therapy with or without bevacizumab in unresectable high-grade serous ovarian cancer: a case-control study. Ann. Surg. Oncol. 22(3), 952–958 (2015).
MedlineGoogle Scholar
29. Daniele G, Lorusso D, Scambia G et al. Feasibility and outcome of interval debulking surgery (IDS) after carboplatin-paclitaxel-bevacizumab (CPB): a subgroup analysis of the MITO-16A-MaNGO OV2A Phase 4 trial. Gynecol. Oncol. 144(2), 256–259 (2017).
Medline CASGoogle Scholar
30. Katsumata N, Yasuda M, Takahashi F et al. 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 374(9698), 1331–1338 (2009).
Medline CASGoogle Scholar
31. Pignata S, Scambia G, Katsaros D et al. Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, Phase 3 trial. Lancet Oncol. 15(4), 396–405 (2014).
Medline CASGoogle Scholar
32. Clamp AR, McNeish I, Dean A et al. 929O_PRICON8: a GCIG Phase III randomised trial evaluating weekly dose- dense chemotherapy integration in first-line epithelial ovarian/fallopian tube/primary peritoneal carcinoma (EOC) treatment: results of primary progression- free survival (PFS) analysis. Ann. Oncol. 28(Suppl. 5), mdx440.039–mdx440.039 (2017).
Google Scholar
33. Gonzalez-Martin A, Gladieff L, Tholander B 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 49(18), 3831–3838 (2013).
Medline CASGoogle Scholar
34. Gonzalez-Martin A, Gladieff L, Tholander B et al. Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer). Eur. J. Cancer 50(4), 862–863 (2014).
MedlineGoogle Scholar
35. Armstrong DK, Bundy B, Wenzel L et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N. Engl. J. Med. 354(1), 34–43 (2006).
Medline CASGoogle Scholar
36. Konner JA, Grabon DM, Gerst SR et al. Phase II study of intraperitoneal paclitaxel plus cisplatin and intravenous paclitaxel plus bevacizumab as adjuvant treatment of optimal stage II/III epithelial ovarian cancer. J. Clin. Oncol. 29(35), 4662–4668 (2011).
Medline CASGoogle Scholar
37. Walker JL, Wenzel L, Huang H, Brady MF. Patient-reported outcomes in GOG 252: NRG oncology study of IV vs IP chemotherapy for ovarian, fallopian, or peritoneal carcinoma. Gynecol. Oncol. 141, 208 (2016).
Google Scholar
38. van Driel WJ, Koole SN, Sikorska K et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N. Engl. J. Med. 378(3), 230–240 (2018).
Medline CASGoogle Scholar
39. Gouy S, Ferron G, Glehen O et al. Results of a multicenter Phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. Gynecol. Oncol. 142(2), 237–242 (2016).
Medline CASGoogle Scholar
40. Herzog TJ, Monk BJ, Rose PG et al. A Phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. Gynecol. Oncol. 132(3), 517–525 (2014).
Medline CASGoogle Scholar
41. Andreas DB, Alexander R, Eric PL, Philipp H, Isabelle RC, Jacobus P. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized Phase 3 multicenter trials. Cancer 115(6), 1234–1244 (2009).
MedlineGoogle Scholar
42. Parmar MK, Ledermann JA, Colombo N et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet 361(9375), 2099–2106 (2003).
Medline CASGoogle Scholar
43. Pfisterer J, Plante M, Vergote I et al. Gemcitabine plus carboplatin compared with carboplatin in patients with platinum-sensitive recurrent ovarian cancer: an intergroup trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG. J. Clin. Oncol. 24(29), 4699–4707 (2006).
Medline CASGoogle Scholar
44. Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E et al. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J. Clin. Oncol. 28(20), 3323–3329 (2010).
Medline CASGoogle Scholar
45. Aghajanian C, Goff B, Nycum LR, Wang Y, Husain A, Blank S. Independent radiologic review: bevacizumab in combination with gemcitabine and carboplatin in recurrent ovarian cancer. Gynecol. Oncol. 133(1), 105–110 (2014).
Medline CASGoogle Scholar
46. Pfisterer J, Shannon C, Hein A et al. 933OCarboplatin/pegylated liposomal doxorubicin/bevacizumab (CD-BEV) vs. carboplatin/gemcitabine/bevacizumab (CG-BEV) in patients with recurrent ovarian cancer: a prospective randomized Phase III ENGOT/GCIG-Intergroup study (AGO study group, AGO-Austria, ANZGOG, GINECO, ANZGOG, GINECO, GINECO, SGCTG). Ann. Oncol. 29(Suppl. 8), viii332–viii358 (2018).
Google Scholar
47. Hanker LC, on behalf of the AGOaGsg, Loibl S et al. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann. Oncol. 23(10), 2605–2612 (2012).
Medline CASGoogle Scholar
48. Husain A, Wang Y, Hanker LC et al. Independent radiologic review of AURELIA, a Phase 3 trial of bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. Gynecol. Oncol. 142(3), 465–470 (2016).
Medline CASGoogle Scholar
49. Bamias A, Gibbs E, Khoon Lee C et al. Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial. Ann. Oncol. 28(8), 1842–1848 (2017).
Medline CASGoogle Scholar
50. Trillsch F, Mahner S, Hilpert F et al. 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 (2016).
Medline CASGoogle Scholar
51. Stockler MR, Hilpert F, Friedlander M 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. 32(13), 1309–1316 (2014).
Medline CASGoogle Scholar
52. Poveda AM, Selle F, Hilpert F et al. 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 (2015).
Medline CASGoogle Scholar
53. Tillmanns TD, Lowe MP, Walker MS, Stepanski EJ, Schwartzberg LS. Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma. Gynecol. Oncol. 128(2), 221–228 (2013).
Medline CASGoogle Scholar
54. Verschraegen CF, Czok S, Muller CY et al. Phase II study of bevacizumab with liposomal doxorubicin for patients with platinum- and taxane-resistant ovarian cancer. Ann. Oncol. 23(12), 3104–3110 (2012).
Medline CASGoogle Scholar
55. Kudoh K, Takano M, Kouta H et al. Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers. Gynecol. Oncol. 122(2), 233–237 (2011).
Medline CASGoogle Scholar
56. Hagemann AR, Novetsky AP, Zighelboim I et al. Phase II study of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer. Gynecol. Oncol. 131(3), 535–540 (2013).
Medline CASGoogle Scholar
57. Musa F, Pothuri B, Blank SV et al. Phase II study of irinotecan in combination with bevacizumab in recurrent ovarian cancer. Gynecol. Oncol. 144(2), 279–284 (2017).
Medline CASGoogle Scholar
58. Monk BJ, Han E, Josephs-Cowan CA, Pugmire G, Burger RA. Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer. Gynecol. Oncol. 102(2), 140–144 (2006).
Medline CASGoogle Scholar
59. Fuh KC, Secord AA, Bevis KS et al. Comparison of bevacizumab alone or with chemotherapy in recurrent ovarian cancer patients. Gynecol. Oncol. 139(3), 413–418 (2015).
Medline CASGoogle Scholar
60. Pietzner K, Richter R, Chekerov R et al. Bevacizumab in heavily pre-treated and platinum resistant ovarian cancer: a retrospective study of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) Ovarian Cancer Study Group. Anticancer Res. 31(8), 2679–2682 (2011).
Medline CASGoogle Scholar
61. O’Malley DM, Richardson DL, Rheaume PS et al. Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer. Gynecol. Oncol. 121(2), 269–272 (2011).
MedlineGoogle Scholar
62. Chura JC, Van Iseghem K, Downs LS, Carson LF, Judson PL. Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer. Gynecol. Oncol. 107(2), 326–330 (2007).
Medline CASGoogle Scholar
63. Monk BJ, Pujade-Lauraine E, Burger RA. Integrating bevacizumab into the management of epithelial ovarian cancer: the controversy of front-line versus recurrent disease. Ann. Oncol. 24(Suppl. 10), x53–x58 (2013).
MedlineGoogle Scholar
64. Rauh-Hain JA, Guseh SH, Esselen KM et al. Patterns of recurrence in patients treated with bevacizumab in the primary treatment of advanced epithelial ovarian cancer. Int. J. Gynecol. Cancer 23(7), 1219–1225 (2013).
MedlineGoogle Scholar
65. von Minckwitz G, Puglisi F, Cortes J 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. 15(11), 1269–1278 (2014).
Medline CASGoogle Scholar
66. Bennouna J, Sastre J, Arnold D et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised Phase 3 trial. Lancet Oncol. 14(1), 29–37 (2013).
Medline CASGoogle Scholar
67. Pignata S, Lorusso D, Joly F et al. Chemotherapy plus or minus bevacizumab for platinum-sensitive ovarian cancer patients recurring after a bevacizumab containing first line treatment: the randomized Phase 3 trial MITO16B-MaNGO OV2B-ENGOT OV17. J. Clin. Oncol. 36(15 Suppl.), 5506–5506 (2018).
Google Scholar
68. Laskey RA, Richard SD, Smith AL et al. Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity. Onco Targets Ther. 7, 469–476 (2014).
MedlineGoogle Scholar
69. Backes FJ, Richardson DL, McCann GA et al. Should bevacizumab be continued after progression on bevacizumab in recurrent ovarian cancer? Int. J. Gynecol. Cancer 23(5), 833–838 (2013).
MedlineGoogle Scholar
70. Eskander RN, Tewari KS. Emerging treatment options for management of malignant ascites in patients with ovarian cancer. Int. J. Womens Health 4, 395–404 (2012).
Medline CASGoogle Scholar
71. Zhao H, Li X, Chen D et al. Intraperitoneal administration of cisplatin plus bevacizumab for the management of malignant ascites in ovarian epithelial cancer: results of a Phase III clinical trial. Med. Oncol. 32(2), 292 (2015).
MedlineGoogle Scholar
72. Tentori L, Lacal PM, Muzi A et al. Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. Eur. J. Cancer 43(14), 2124–2133 (2007).
Medline CASGoogle Scholar
73. Liu JF, Barry WT, Birrer M et al. 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 (2014).
Medline CASGoogle Scholar
74. Moore K, Colombo N, Scambia G et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med. 379(26), 2495–2505 (2018).
Google Scholar
75. Mirza MR, Wang J, Mau-Sørensen M et al. 953PA Phase 1 study to evaluate the safety and tolerability of bevacizumab-niraparib combination therapy and determine the recommended Phase 2 dose (RP2D) in women with platinum-sensitive epithelial ovarian cancer (ENGOT-OV24/AVANOVA1). Ann. Oncol. 28(Suppl. 5), mdx372.024–mdx372.024 (2017).
Google Scholar
76. Lu JF, Bruno R, Eppler S, Novotny W, Lum B, Gaudreault J. Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother. Pharmacol. 62(5), 779–786 (2008).
Medline CASGoogle Scholar
77. Smerdel MP, Steffensen KD, Waldstrøm M, Brandslund I, Jakobsen A. The predictive value of serum VEGF in multiresistant ovarian cancer patients treated with bevacizumab. Gynecol. Oncol. 118(2), 167–171 (2010).
Medline CASGoogle Scholar
78. Wimberger P, Chebouti I, Kasimir-Bauer S et al. Explorative investigation of vascular endothelial growth factor receptor expression in primary ovarian cancer and its clinical relevance. Gynecol. Oncol. 133(3), 467–472 (2014).
Medline CASGoogle Scholar
79. Raja FA, Hook JM, Ledermann JA. Biomarkers in the development of anti-angiogenic therapies for ovarian cancer. Cancer Treat. Rev. 38(6), 662–672 (2012).
Medline CASGoogle Scholar
80. Schultheis AM, Lurje G, Rhodes KE et al. Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab. Clin. Cancer Res. 14(22), 7554–7563 (2008).
Medline CASGoogle Scholar
81. Han ES, Burger RA, Darcy KM et al. Predictive and prognostic angiogenic markers in a gynecologic oncology group Phase II trial of bevacizumab in recurrent and persistent ovarian or peritoneal cancer. Gynecol. Oncol. 119(3), 484–490 (2010).
Medline CASGoogle Scholar
82. Bais C, Mueller B, Brady MF et al. Tumor microvessel density as a potential predictive marker for bevacizumab benefit: GOG-0218 biomarker analyses. J. Natl Cancer Inst. 109(11), doi:10.1093/jnci/djx066 (2017).
MedlineGoogle Scholar
83. Backen A, Renehan AG, Clamp AR et al. The combination of circulating Ang1 and Tie2 levels predicts progression-free survival advantage in bevacizumab-treated patients with ovarian cancer. Clin. Cancer Res. 20(17), 4549–4558 (2014).
Medline CASGoogle Scholar
84. Collinson F, Hutchinson M, Craven RA et al. Predicting response to bevacizumab in ovarian cancer: a panel of potential biomarkers informing treatment selection. Clin. Cancer Res. 19(18), 5227–5239 (2013).
Medline CASGoogle Scholar
85. Karihtala P, Mäenpää J, Turpeenniemi-Hujanen T, Puistola U. Front-line bevacizumab in serous epithelial ovarian cancer: biomarker analysis of the FINAVAST trial. Anticancer Res. 30(3), 1001–1006 (2010).
Medline CASGoogle Scholar
86. Boisen MK, Madsen CV, Dehlendorff C, Jakobsen A, Johansen JS, Steffensen KD. The prognostic value of plasma YKL-40 in patients with chemotherapy-resistant ovarian cancer treated with bevacizumab. Int. J. Gynecol. Cancer 26(8), 1390–1398 (2016).
MedlineGoogle Scholar
87. Steffensen KD, Madsen CV, Andersen RF, Waldstrøm M, Adimi P, Jakobsen A. Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab. Eur. J. Cancer 50(15), 2611–2618 (2014).
Medline CASGoogle Scholar
88. Chan JK, Kiet TK, Blansit K et al. MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian cancer. Gynecol. Oncol. 133(3), 568–574 (2014).
Medline CASGoogle Scholar
89. Norquist BM, Brady MF, Harrell MI et al. Mutations in homologous recombination genes and outcomes in ovarian carcinoma patients in GOG 218: an NRG Oncology/Gynecologic Oncology Group Study. Clin. Cancer Res. 24(4), 777 (2018).
Medline CASGoogle Scholar
90. Ng CS, Zhang Z, Lee SI et al. CT perfusion as an early biomarker of treatment efficacy in advanced ovarian cancer: an ACRIN and GOG study. Clin. Cancer Res. 23(14), 3684–3691 (2017).
Medline CASGoogle Scholar
91. Previs RA, Bevis KS, Huh W et al. A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy. Gynecol. Oncol. 132(3), 531–536 (2014).
Medline CASGoogle Scholar
92. Slaughter KN, Thai T, Penaroza S et al. Measurements of adiposity as clinical biomarkers for first-line bevacizumab-based chemotherapy in epithelial ovarian cancer. Gynecol. Oncol. 133(1), 11–15 (2014).
Medline CASGoogle Scholar
93. Azad NS, Annunziata CM, Steinberg SM et al. Lack of reliability of CA125 response criteria with anti‐VEGF molecularly targeted therapy. Cancer 112(8), 1726–1732 (2008).
Medline CASGoogle Scholar
94. Randall LM, Sill MW, Burger RA, Monk BJ, Buening B, Sorosky JI. Predictive value of serum CA-125 levels in patients with persistent or recurrent epithelial ovarian cancer or peritoneal cancer treated with bevacizumab on a Gynecologic Oncology Group Phase II trial. Gynecol. Oncol. 124(3), 563–568 (2012).
Medline CASGoogle Scholar
95. Dao MD, Alwan LM, Gray HJ, Tamimi HK, Goff BA, Liao JB. Recurrence patterns after extended treatment with bevacizumab for ovarian, fallopian tube, and primary peritoneal cancers. Gynecol. Oncol. 130(2), 295–299 (2013).
Medline CASGoogle Scholar
96. Mir O, Coriat R, Cabanes L et al. An observational study of bevacizumab-induced hypertension as a clinical biomarker of antitumor activity. Oncologist 16(9), 1325–1332 (2011).
Medline CASGoogle Scholar
97. Itatani Y, Kawada K, Yamamoto T, Sakai Y. Resistance to anti-angiogenic therapy in cancer-alterations to anti-VEGF pathway. Int. J. Mol. Sci. 19(4), 1232 (2018).
Google Scholar
98. Guerrouahen BS, Pasquier J, Kaoud NA et al. Akt-activated endothelium constitutes the niche for residual disease and resistance to bevacizumab in ovarian cancer. Mol. Cancer Ther. 13(12), 3123–3136 (2014).
Medline CASGoogle Scholar
99. Mitamura T, Pradeep S, McGuire M et al. Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP). Oncogene 37, 722 (2017).
MedlineGoogle Scholar
100. Iwai T, Sugimoto M, Harada S, Yorozu K, Kurasawa M, Yamamoto K. Continuous administration of bevacizumab plus capecitabine, even after acquired resistance to bevacizumab, restored anti-angiogenic and antitumor effect in a human colorectal cancer xenograft model. Oncol. Rep. 36(2), 626–632 (2016).
Medline CASGoogle Scholar

Vol. 16, No. 7

Metrics

Downloaded 730 times

History

Received 23 January 2019

Accepted 15 July 2019

Published online 20 November 2019

Published in print March 2020

Information

Keywords

Financial & competing interests disclosure

This paper is funded in or in part, from direct NIH funding, grant number: 2T32CA060396. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Company review disclosure

In addition to the peer-review process, with the authors’ consent, the manufacturer of the product discussed in this article was given the opportunity to review the manuscript for factual accuracy. Changes were made by the authors at their discretion and based on scientific or editorial merit only. The authors maintained full control over the manuscript, including content, wording and conclusions.

PDF download

Bevacizumab use in the frontline, maintenance and recurrent settings for ovarian cancer

Abstract

References