Primary ovarian cancer: possibilities for improving treatment outcomes
https://doi.org/10.21518/2079-701X-2019-19-150-156
Abstract
Ovarian cancer is the fifth leading cause of cancer-related death among women in the world. In spite of recent progress in treatment strategy, around 70 % of ovarian cancer patients relapse. The cytoreductive surgery followed by platinum-, taxane-containing chemotherapy is the standard approach to the primary treatment of ovarian cancer; a variant of neoadjuvant chemotherapy with interval cytoreduction may be used in patients with stage IIIC-IV disease.
Given that angiogenesis plays a central role in progression of solid tumour growth and metastasis, recent studies have focused on anti-angiogenic treatment. Bevacizumab, a humanized IgG monoclonal antibody that inhibits the vascular endothelial growth factor receptor, is most promising antiangiogenic drug. Bevacizumab was approved on December 23, 2011 by the European Medicines Agency and on June 13, 2018 by the Food and Drug Administration as first-line treatment in epithelial ovarian, fallopian tube or primary peritoneal cancer stage III or IV in combination with carboplatin and paclitaxel. Based on sub-analyses, the recommended dosage of bevacizumab is 15 mg/kg every 3 weeks for a total of 22 cycles. Bevacizumab is a well-studied drug with a favourable safety profile that has been used in routine clinical practice for more than 10 years. However, the search for predictors to identify the category of patients, who will benefit most from bevacizumab therapy, is still in progress, and clinical trials that may improve the therapeutic potential in treating ovarian cancer in the near future due to introduction of new combinations of bevacizumab with PARP inhibitors and immuno-oncological drugs are under way. In view of acquisition of mature clinical trial data, a range of the most discussed issues regarding optimal use of bevacizumab in patients with ovarian cancer has been identified.
Given that angiogenesis plays a central role in progression of solid tumour growth and metastasis, recent studies have focused on anti-angiogenic treatment. Bevacizumab, a humanized IgG monoclonal antibody that inhibits the vascular endothelial growth factor receptor, is most promising antiangiogenic drug. Bevacizumab was approved on December 23, 2011 by the European Medicines Agency and on June 13, 2018 by the Food and Drug Administration as first-line treatment in epithelial ovarian, fallopian tube or primary peritoneal cancer stage III or IV in combination with carboplatin and paclitaxel. Based on sub-analyses, the recommended dosage of bevacizumab is 15 mg/kg every 3 weeks for a total of 22 cycles. Bevacizumab is a well-studied drug with a favourable safety profile that has been used in routine clinical practice for more than 10 years. However, the search for predictors to identify the category of patients, who will benefit most from bevacizumab therapy, is still in progress, and clinical trials that may improve the therapeutic potential in treating ovarian cancer in the near future due to introduction of new combinations of bevacizumab with PARP inhibitors and immuno-oncological drugs are under way. In view of acquisition of mature clinical trial data, a range of the most discussed issues regarding optimal use of bevacizumab in patients with ovarian cancer has been identified.
About the Author
S. V. Khokhlova
National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Dr. of Sci. (Med.), Head of Department of Anticancer Drug Therapy
4 Akademika Oparina Street, Moscow, 117997, Russia
References
1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30. doi: 10.3322/caac.21442.
2. Ledermann J.A., Raja F.A., Fotopoulou C., et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi24–vi32. doi: 10.1093/annonc/mdy157.
3. Schorge J.O., Eisenhauer E.E., Chi D.S. Current surgical management of ovarian cancer. Hematol Oncol Clin North Am. 2012;26(1):93–109. doi: 10.1016/j.hoc.2011.10.004.
4. The European Medicines Agency. European public assessment report. Avastin product information. Avastin-H-C-582-II-23, August 2008. Available at: http://www.emea.europa.eu/docs/en_GB/document_ library/EPAR_–_Assessment_Report_–_Variation/human/000582/WC500029270.pdf. Accessed January 24, 2009.
5. Shih T., Lindley C. Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies. Clin Ther. 2006;28(11):1779–1802. doi: 10.1016/j.clinthera.2006.11.015.
6. Perren T.J., Swart A.M., Pfisterer J., et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484–2496. doi: 10.1056/NEJMoa1103799.
7. Oza A.M., Cook A.D., Pfisterer J., et al. ICON7 trial investigators. 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(8):928–936. doi: 10.1016/S1470-2045(15)00086-8.
8. Wade K.N.S., Brady M.F., Thai T., Wang Y., Zheng B., Salani R., Tewari K.S., Gray H.J., Bakkum-Gamez J.N., Burger R.A., Moore K.N., Bookman M.A. Measurements of adiposity as prognostic biomarkers for survival with antiangiogenic treatment in epithelial ovarian cancer: An NRG Oncology/Gynecologic Oncology Group ancillary data analysis of GOG 218. Clin Cancer Res. 2018;24(4):777-783. doi: 10.1158/1078-0432.CCR-17-1327.
9. Measurements of adiposity as prognostic biomarkers for survival with anti-angiogenic treatment in epithelial ovarian cancer: An NRG Oncology/Gynecologic Oncology Group ancillary data analysis of GOG 218. Clin Cancer Res. 2018;24(4):777-783. doi: 10.1158/1078-0432.CCR-17-1327.
10. Stuart G., Avall-Lundqvist E., Du Bois A., et al. 3rd international ovarian cancer consensus Conference: outstanding issues for future consideration. Ann Oncol. 2005;16(suppl 8):viii36–viii38. doi: 10.1093/annonc/mdi965.
11. Bergmann T.K., Gréen H., Brasch-Andersen C., et al. Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer. Eur J Clin Pharmacol. 2011;67(7):693–700. doi: 10.1007/s00228-011-1007-6.
12. Komatsu M., Wheeler H.E., Chung S., et al. Pharmacoethnicity in paclitaxel-induced sensory peripheral neuropathy. Clin Cancer Res. 2015;21(19):4337–4346. doi: 10.1158/1078-0432.CCR-15-0133.
13. Pignata S., Scambia G., Katsaros D., et al. Gynecologic Cancer InterGroup (GCIG) Investigators. 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. 2014;15(4):396–405. doi: 10.1016/S1470-2045(14)70049-X.
14. Academic.oup.com. ICON8: 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. Available at: https://academic.oup.com/annonc/article/28/suppl_5/ mdx440.039/4109951. Accessed January 18, 2019.
15. Marchetti C., De Felice F., Di Pinto A., et al. Dose-dense Weekly chemotherapy in advanced ovarian cancer: an updated metaanalysis of randomized controlled trials. Crit Rev Oncol Hematol. 2018;(125):30–34. doi: 10.1016/j.critrevonc.2018.02.016.
16. Gonzalez-Martin A., Gladieff L., Tholander B. et al. OCTAVIA Investigators. 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(18):3831–3838. doi: 10.1016/j.ejca.2013.08.002.
17. Gonzalez-Martin A., Gladieff L., Tholander B., et al. OCTAVIA Investigators. Updated results from OCTAVIA (front-line bevacizumab, carboplatin and weekly paclitaxel therapy for ovarian cancer). Eur J Cancer. 2014;50(4):862–863. doi: 10.1016/j.ejca.2013.12.001.
18. Chan J.K., Brady M.F., Penson R.T., et al. Weekly vs. Every-3-Week paclitaxel and carboplatin for ovarian cancer. N Engl J Med. 2016;374(8):738–748. doi: 10.1056/NEJMoa1505067.
19. Highlights of prescribing information. AVASTIN (bevacizumab) injection, for intravenous use Initial U.S. Approval: 2004. Available at: https://www.gene.com/download/pdf/avastin_prescribing.pdf.
20. FDA Approves Genentech’s Avastin (Bevacizumab) Plus Chemotherapy as a Treatment for Women With Advanced Ovarian Cancer Following Initial Surgery [webpage on the Internet]. June 2018. Available at: http://ovarian.org/about-ovarian-cancer/treatment/493-2018-06-13-21-09-18. Accessed January 18, 2019.
21. Oza A.M., 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. 2017;27(1):50–58. doi: 10.1097/IGC.0000000000000836.
22. A prospective randomised phase III trial to evaluate optimal treatment duration of firstline bevacizumab in combination with carboplatin and paclitaxel in patients with primary epithelial ovarian, fallopian tube or peritoneal cancer. AGO-OVAR17. Ongoing, NCT number: NCT01462890, ClinicalTrials.gov.
23. Selle F., Colombo N., Korach J., et al. Safety and efficacy of extended bevacizumab therapy in elderly ($70 years) versus younger patients treated for newly diagnosed ovarian cancer in the International ROSiA study. Int J Gynecol Cancer. 2018;28(4):729–737. doi: 10.1097/IGC.0000000000001221.
24. Perren T.J., Swart A.M., Pfisterer J. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. doi:10.1056/NEJMoa1103799.
25. Kommoss S., Winterhoff B., Oberg A.L., et al. Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes. Clin Cancer Res. 2017;23(14):3794–3801. doi: 10.1158/1078-0432.CCR-16-2196.
26. Marchetti C., Romito A., Musella A., et al. Combined plasma fibrinogen and neutrophil lymphocyte ratio in ovarian cancer prognosis may play a role? Int J Gynecol Cancer. 2018;28(5):939–944. doi: 10.1097/IGC.0000000000001233.
27. Farolfi A., Petrone M., Scarpi E., et al. Inflammatory indexes as prognostic and predictive factors in ovarian cancer treated with chemotherapy alone or together with bevacizumab. A multicenter, retrospective analysis by the MITO group (MITO 24). Target Oncol. 2018;13(4):469–479. doi: 10.1007/s11523-018-0574-1.
28. Stuart G.C., Kitchener H., Bacon M., et al. 2010 gynecologic cancer intergroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the fourth ovarian cancer consensus Conference. Int J Gynecol Cancer. 2011;21(4):750–755. doi: 10.1097/IGC.0b013e31821b2568.
29. National Comprehensive Cancer Network. Epithelial ovarian cancer, including fallopian tube cancer and primary peritoneal cancer, 2015 ver1. 2015. Available from: http://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Accessed January 18, 2019.
30. Vergote I., Tropé C.G., Amant F., et al. NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):943–953. doi: 10.1200/JCO.2011.36.9785.
31. Kehoe S., Hook J., Nankivell M., et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (chorus): an open-label, randomised, controlled, non-inferiority trial. The Lancet. 2015;386(9990):249–257. doi: 10.1016/S0140-6736(14)62223-6.
32. Rouzier R., Gouy S., Selle F., et al. Efficacy and safety of bevacizumabcontaining neoadjuvant therapy followed by interval debulking surgery in advanced ovarian cancer: results from the ANTHALYA trial. Eur J Cancer. 2017;(70):133–142. doi: 10.1016/j.ejca.2016.09.036.
33. 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. 2017;144(2):256–259. doi: 10.1016/j.ygyno.2016.12.011.
34. Salani R., O’Malley D.M., Copeland L.J., et al. Feasibility of interval cytoreduction following neoadjuvant chemotherapy with carboplatin, weekly paclitaxel, and bevacizumab for advanced ovarian cancer – a phase 1 study. Int J Gynecol Cancer. 2014;24(4):682–686. doi: 10.1097/IGC.0000000000000107.
35. 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. 2015;22(S3):S952–S958. doi: 10.1245/s10434-015-4651-8.
36. RandomizedA Arandomized. Open-label, multicentric phase II trial of pembrolizumab (Keytruda®) with chemotherapy versus chemotherapy alone (standard of care) as neo adjuvant treatment of ovarian cancer not amenable to front line debulking surgery. NEOPEMBROV. Ongoing, NCT number: NCT03275506, ClinicalTrials.gov.
37. A phase III, multicenter, randomized, study of Atezolizumab versus placebo administered in combination with paclitaxel, carboplatin, and bevacizumab to patients with NewlyDiagnosed stage III or stage IV ovarian, fallopian tube, or primary peritoneal cancer. IMagyn050. Ongoing, NCT number: NCT03038100, ClinicalTrials.gov.
38. A Randomized Phase II Trial of Avastin (A) or Avastin and Erlotinib (AE) as First Line Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Newly Diagnosed Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors. Ongoing, NCT number: NCT00520013, ClinicalTrials.gov.
39. A randomized phase II trial of CarboplatinPaclitaxelBevacizumab vs CarboplatinPaclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib in patients with advanced (stage III B-C-IV) ovarian, primary peritoneal and fallopian tube cancer preceded by a phase I dose escalation study on Rucaparib-Bevacizumab combination. MITO 25. Ongoing, NCT number: NCT03462212, ClinicalTrials.gov.
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For citations:
Khokhlova SV. Primary ovarian cancer: possibilities for improving treatment outcomes. Meditsinskiy sovet = Medical Council. 2019;(19):150-156. (In Russ.) https://doi.org/10.21518/2079-701X-2019-19-150-156
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