Advances in ovarian cancer therapy

Alexander J Cortez, Patrycja Tudrej, Katarzyna A Kujawa, Katarzyna M Lisowska, Alexander J Cortez, Patrycja Tudrej, Katarzyna A Kujawa, Katarzyna M Lisowska

Abstract

Epithelial ovarian cancer is typically diagnosed at an advanced stage. Current state-of-the-art surgery and chemotherapy result in the high incidence of complete remissions; however, the recurrence rate is also high. For most patients, the disease eventually becomes a continuum of symptom-free periods and recurrence episodes. Different targeted treatment approaches and biological drugs, currently under development, bring the promise of turning ovarian cancer into a manageable chronic disease. In this review, we discuss the current standard in the therapy for ovarian cancer, major recent studies on the new variants of conventional therapies, and new therapeutic approaches, recently approved and/or in clinical trials. The latter include anti-angiogenic therapies, polyADP-ribose polymerase (PARP) inhibitors, inhibitors of growth factor signaling, or folate receptor inhibitors, as well as several immunotherapeutic approaches. We also discuss cost-effectiveness of some novel therapies and the issue of better selection of patients for personalized treatment.

Keywords: Biological drugs; Clinical trials; Ovarian cancer; Targeted therapy.

References

    1. Kurman RJ, Shih IM. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-shifting the paradigm. Hum Pathol. 2011;42(7):918–931. doi: 10.1016/j.humpath.2011.03.003.
    1. Kujawa KA, Lisowska KM. Ovarian cancer—from biology to clinic. Postep Hig Med Dosw. 2015;69:1275–1290. doi: 10.5604/17322693.1184451.
    1. Bignotti E, Tassi RA, Calza S, Ravaggi A, Bandiera E, Rossi E, Donzelli C, Pasinetti B, Pecorelli S, Santin AD. Gene expression profile of ovarian serous papillary carcinomas: identification of metastasis-associated genes. Am J Obstet Gynecol. 2007;196(3):245–246. doi: 10.1016/j.ajog.2006.10.874.
    1. Lisowska KM, Olbryt M, Student S, Kujawa KA, Cortez AJ, Simek K, Dansonka-Mieszkowska A, Rzepecka IK, Tudrej P, Kupryjanczyk J. Unsupervised analysis reveals two molecular subgroups of serous ovarian cancer with distinct gene expression profiles and survival. J Cancer Res Clin. 2016;142(6):1239–1252. doi: 10.1007/s00432-016-2147-y.
    1. Lisowska KM, Olbryt M, Dudaladava V, Pamula-Pilat J, Kujawa K, Grzybowska E, Jarzab M, Student S, Rzepecka IK, Jarzab B, Kupryjanczyk J. Gene expression analysis in ovarian cancer—faults and hints from DNA microarray study. Front Oncol. 2014;4:6. doi: 10.3389/fonc.2014.00006.
    1. Basta A, Bidziński M, Bieńkiewicz A, Blecharz P, Bodnar L, Jach R, Knapp P, Kojs Z, Kotarski J, Markowska J, Misiek M, Sznurkowski J, Wicherek Ł, Sawicki W, Timorek A, Bahyrycz J, Mądry R. Recommendation of the Polish society of oncological gynaecology on the diagnosis and treatment of epithelial ovarian cancer. Oncol Clin Pract. 2015;11(5):11.
    1. Cho KR, Shih IM. Ovarian cancer. Annu Rev Pathol Mech Dis. 2009;4:287–313. doi: 10.1146/annurev.pathol.4.110807.092246.
    1. Prat J, Oncology FCoG. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet. 2014;124(1):1–5. doi: 10.1016/j.ijgo.2013.10.001.
    1. du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO) Cancer. 2009;115(6):1234–1244. doi: 10.1002/cncr.24149.
    1. E. SGO.Guidelines ESoGO . Advanced (stage III-IV) ovarian cancer surgery. Quality indicators. Complete report. Praque: ESGO; 2015.
    1. Eisenhauer EA, Therasse T, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45:19. doi: 10.1016/j.ejca.2008.10.026.
    1. Foley OW, Rauh-Hain JA, del Carmen MG. Recurrent epithelial ovarian cancer: an update on treatment. Oncol N Y. 2013;27(4):288-+.
    1. Rustin GJ, van der Burg ME, Griffin CL, Guthrie D, Lamont A, Jayson GC, Kristensen G, Mediola C, Coens C, Qian W, Parmar MK, Swart AM, Mrc OV, investigators E Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet. 2010;376(9747):1155–1163. doi: 10.1016/S0140-6736(10)61268-8.
    1. Friedlander M, Trimble E, Tinker A, Alberts D, Avall-Lundqvist E, Brady M, Harter P, Pignata S, Pujade-Lauraine E, Sehouli J, Vergote I, Beale P, Bekkers R, Calvert P, Copeland L, Glasspool R, Gonzalez-Martin A, Katsaros D, Kim JW, Miller B, Provencher D, Rubinstein L, Atri M, Zeimet A, Bacon M, Kitchener H, Stuart GCE, InterGrp GC. Clinical trials in recurrent ovarian cancer. Int J Gynecol Cancer. 2011;21(4):771–775. doi: 10.1097/IGC.0b013e31821bb8aa.
    1. EMA . EMA approval: avastin autorization details. UK: EMA; 2009.
    1. Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, Ochiai K, Noda K, Grp JGO. Dose-dense paclitaxel once a week in combination with carboplatin every 3weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009;374(9698):1331–1338. doi: 10.1016/S0140-6736(09)61157-0.
    1. Katsumata N, Yasuda M, Isonishi S, Takahashi F, Michimae H, Kimura E, Aoki D, Jobo T, Kodama S, Terauchi F, Sugiyama T, Ochiai K, Grp JGO. 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(10):1020–1026. doi: 10.1016/S1470-2045(13)70363-2.
    1. Chan JK, Brady MF, Penson RT, Huang H, Birrer MJ, Walker JL, DiSilvestro PA, Rubin SC, Martin LP, Davidson SA, Huh WK, O’Malley DM, Boente MP, Michael H, Monk BJ. Weekly vs. every-3-week paclitaxel and carboplatin for ovarian cancer. N Engl J Med. 2016;374(8):738–748. doi: 10.1056/NEJMoa1505067.
    1. ICON8. Trial. . Accessed 30 Oct 2017
    1. van Meurs HS, Tajik P, Hof MHP, Vergote I, Kenter GG, Mol BJ, Buist MR, Bossuyt PM. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European organisation for research and treatment of cancer 55971 randomised trial. Eur J Cancer. 2013;49(15):3191–3201. doi: 10.1016/j.ejca.2013.06.013.
    1. Jaaback K, Johnson N, Lawrie TA (2016) Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer (review). Cochrane Database Syst Rev (1):CD005340. 10.1002/14651858.CD005340.pub4
    1. Walker J, Brady MF, DiSilvestro PA, et al. A phase III trial of bevacizumab with IV versus IP chemotherapy for ovarian, fallopian tube, and peritoneal carcinoma: an NRG Oncology Study. Gynecol Oncol. 2016;141:208.
    1. Urbański K. Consolidation therapy of ovarian cancer. Onkologia w Praktyce Klinicznej. 2007;3(6):8.
    1. Lopez-Guerrero JA, Romero I, Poveda A. Trabectedin therapy as an emerging treatment strategy for recurrent platinum-sensitive ovarian cancer. Chin J Cancer. 2015;34(1):41–49. doi: 10.5732/cjc.014.10278.
    1. Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012;48(15):2361–2368. doi: 10.1016/j.ejca.2012.04.001.
    1. Lorusso D, Scambia G, Pignata S, Sorio R, Amadio G, Lepori S, Mosconi A, Pisano C, Mangili G, Maltese G, Sabbatini R, Artioli G, Gamucci T, Di Napoli M, Capoluongo E, Ludovini V, Raspagliesi F, Ferrandina G. Prospective phase II trial of trabectedin in BRCAmutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial. Ann Oncol. 2016;27:6. doi: 10.1093/annonc/mdv608.
    1. Laas E, Luyckx M, De Cuypere M, Selle F, Darai E, Querleu D, Rouzier R, Chereau E. Secondary complete cytoreduction in recurrent ovarian cancer benefit of optimal patient selection using scoring system. Int J Gynecol Cancer. 2014;24(2):238–246. doi: 10.1097/IGC.0000000000000051.
    1. Harter P, Sehouli J, Reuss A, Hasenburg A, Scambia G, Cibula D, Mahner S, Vergote I, Reinthaller A, Burges A, Hanker L, Polcher M, Kurzeder C, Canzler U, Petry KU, Obermair A, Petru E, Schmalfeldt B, Lorusso D, du Bois A. Prospective validation study of a predictive score for operability of recurrent ovarian cancer the multicenter intergroup study DESKTOP II. A project of the AGO Kommission OVAR, AGO study group, NOGGO, AGO-Austria, and MITO. Int J Gynecol Cancer. 2011;21(2):289–295. doi: 10.1097/IGC.0b013e31820aaafd.
    1. Wolford JE, Tewari KS. Highlights from the gynecologic oncology track at the 2017 annual meeting of the American society of clinical oncology. J Gynecol Oncol. 2017;28(5):1–12. doi: 10.3802/jgo.2017.28.e74.
    1. AGO-OVAR. Trials. . Accessed 30 Oct 2017
    1. ICON9. Trial. . Accessed 30 Oct 2017
    1. Rutkowski P, Śpiewankiewicz B, Herman K, Jastrzębski T, Kładny J, Kojs Z, Krzakowski M, Polkowski W, Wyrwicz L, Wysocki P, Zdzienicki M, Zegarski W. Polish clinical practice guidelines on hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductice surgery (CRS) in peritoneal malignancy treatment. Nowotw J Oncol. 2014;64(6):7.
    1. Bhatt A, Glehen O. The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer: a review. India J Surg Oncol. 2016;7(2):188–197. doi: 10.1007/s13193-016-0501-9.
    1. Śpiewankiewicz B, Osuch B, Kuśnierz J, Symonides M, Smorczewska M. Hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of patients with disseminated intraperitoneal malignancy: preliminary report. Curr Gynecol Oncol. 2013;11(1):9. doi: 10.15557/CGO.2013.0003.
    1. Bakrin N, Cotte E, Golfier F, Gilly FN, Freyer G, Helm W, Glehen O, Bereder JM. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for persistent and recurrent advanced ovarian carcinoma: a multicenter, prospective study of 246 patients. Ann Surg Oncol. 2012;19:7. doi: 10.1245/s10434-012-2510-4.
    1. Jain RK. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell. 2014;26(5):605–622. doi: 10.1016/j.ccell.2014.10.006.
    1. FDA Approval for Bevacizumab. . Accessed 30 Oct 2017
    1. Roche (2011) Roche medicine avastin receives EU approval for the treatment of women with recurrent, platinum-sensitive ovarian cancer. . Accessed 30 Oct 2017
    1. Aravantinos G, Pectasides D. Bevacizumab in combination with chemotherapy for the treatment of advanced ovarian cancer: a systematic review. J Ovarian Res. 2014;7:57. doi: 10.1186/1757-2215-7-57.
    1. Rossi L, Verrico M, Zaccarelli E, Papa A, Colonna M, Strudel M, Vici P, Bianco V, Tomao F. Bevacizumab in ovarian cancer: a critical review of phase III studies. Oncotarget. 2017;8(7):12389–12405.
    1. Tewari KS, Java JJ, Eskander RN, Monk BJ, Burger RA. Early initiation of chemotherapy following complete resection of advanced ovarian cancer associated with improved survival: NRG oncology/gynecologic oncology group study. Ann Oncol. 2016;27(1):114–121. doi: 10.1093/annonc/mdv500.
    1. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX, Grp GO. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473–2483. doi: 10.1056/NEJMoa1104390.
    1. Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stahle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian WD, Parmar MKB, Oza AM, Investigators I. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484–2496. doi: 10.1056/NEJMoa1103799.
    1. Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Park-Simon TW, Rustin G, Joly F, Mirza MR, Plante M, Quinn M, Poveda A, Jayson GC, Stark D, Swart AM, Farrelly L, Kaplan R, Parmar MKB, Perren TJ, Investigators IT. 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.
    1. Aghajanian C. The role of bevacizumab in ovarian cancer—an evolving story. Gynecol Oncol. 2006;102(2):131–133. doi: 10.1016/j.ygyno.2006.06.014.
    1. Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32(13):1302–1308. doi: 10.1200/JCO.2013.51.4489.
    1. 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. 2015;139(1):10–16. doi: 10.1016/j.ygyno.2015.08.004.
    1. Marchetti C, De Felice F, Palaia I, Musella A, Di Donato V, Gasparri ML, Musio D, Muzii L, Tombolini V, Panici PB. Efficacy and toxicity of bevazicumab in recurrent ovarian disease: an update meta-analysis on phase III trials. Oncotarget. 2015;7(11):7.
    1. Yi S, Zeng LO, Kuang Y, Cao Z, Zheng C, Zhang Y, Liao M, Yang L. Anti-angiogenic drugs used with chemotherapy for patients with recurrent ovarian cancer: a meta-analysis. Oncotargets Ther. 2017;10:973–984. doi: 10.2147/OTT.S119879.
    1. Rouzier R, Gouy S, Selle F, Lambaudie E, Floquet A, Fourchotte V, Pomel C, Colombo PE, Kalbacher E, Martin-Francoise S, Fauvet R, Follana P, Lesoin A, Lecuru F, Ghazi Y, Dupin J, Chereau E, Zohar S, Cottu P, Joly F. 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. 2017;70:133–142. doi: 10.1016/j.ejca.2016.09.036.
    1. Coleman RL (2016) Molecular therapeutics in in epithelial ovarian cancer. In: Oral presentation at 16th Biennial Meeting of the International Gynecologic Cancer Society, Lisbon
    1. Goswami KK, Ghosh T, Ghosh S, Sarkar M, Bose A, Baral R. Tumor promoting role of anti-tumor macrophages in tumor microenvironment. Cell Immunol. 2017;316:10. doi: 10.1016/j.cellimm.2017.04.005.
    1. Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, Rey-Giraud F, Pradel LP, Feuerhake F, Klaman I, Jones T, Jucknischke U, Scheiblich S, Kaluza K, Gorr IH, Walz A, Abiraj K, Cassier PA, Sica A, Gomez-Roca C, de Visser KE, Italiano A, Le Tourneau C, Delord JP, Levitsky H, Blay JY, Ruttinger D. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25(6):846–859. doi: 10.1016/j.ccr.2014.05.016.
    1. Konecny GE, Kristeleit RS. PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions. Br J Cancer. 2016;115(10):1157–1173. doi: 10.1038/bjc.2016.311.
    1. Chan JK, Herzog TJ, Hu LL, Monk BJ, Kiet T, Blansit K, Kapp DS, Yu XH. Bevacizumab in treatment of high-risk ovarian cancer-a cost-effectiveness analysis. Oncologist. 2014;19(5):523–527. doi: 10.1634/theoncologist.2013-0322.
    1. Duong M, Wright E, Yin L, Martin-Nunez I, Ghatage P, Fung-Kee-Fung M. The cost-effectiveness of bevacizumab for the treatment of advanced ovarian cancer in Canada. Curr Oncol. 2016;23(5):E461–E467. doi: 10.3747/co.23.3139.
    1. Hinde S, Epstein D, Cook A, Embleton A, Perren T, Sculpher M. The cost-effectiveness of bevacizumab in advanced ovarian cancer using evidence from the ICON7 trial. Value Health. 2016;19(4):431–439. doi: 10.1016/j.jval.2016.01.013.
    1. Raja FA, Griffin CL, Qian W, Hirte H, Parmar MK, Swart AM, Ledermann JA. Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer. Brit J Cancer. 2011;105(7):884–889. doi: 10.1038/bjc.2011.334.
    1. Ledermann JA, Embleton AC, Raja F, Perren TJ, Jayson GC, Rustin GJS, Kaye SB, Hirte H, Eisenhauer E, Vaughan M, Friedlander M, Gonzalez-Martin A, Stark D, Clark E, Farrelly L, Swart AM, Cook A, Kaplan RS, Parmar MKB, Collaborators I. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;387(10023):1066–1074. doi: 10.1016/S0140-6736(15)01167-8.
    1. Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F, investigators M. 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. 2015;16(5):561–568. doi: 10.1016/S1470-2045(15)70115-4.
    1. du Bois A, Floquet A, Kim JW, Rau J, del Campo JM, Friedlander M, Pignata S, Fujiwara K, Vergote I, Colombo N, Mirza MR, Monk BJ, Kimmig R, Ray-Coquard I, Zang R, Diaz-Padilla I, Baumann KH, Mouret-Reynier MA, Kim JH, Kurzeder C, Lesoin A, Vasey P, Marth C, Canzler U, Scambia G, Shimada M, Calvert P, Pujade-Lauraine E, Kim BG, Herzog TJ, Mitrica I, Schade-Brittinger C, Wang Q, Crescenzo R, Harter P. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol. 2014;32(30):3374–3382. doi: 10.1200/JCO.2014.55.7348.
    1. Floquet A, Vergote I, Colombo N, Fiane B, Monk BJ, Reinthaller A, Calvert P, Herzog TJ, Meier W, Kim JW, del Campo JM, Friedlander M, Pisano C, Isonishi S, Crescenzo RJ, Barrett C, Wang K, Mitrica I, du Bois A. Progression-free survival by local investigator versus independent central review: comparative analysis of the AGO-OVAR16 Trial. Gynecol Oncol. 2015;136(1):37–42. doi: 10.1016/j.ygyno.2014.11.074.
    1. Awasthi N, Schwarz RE. Profile of nintedanib in the treatment of solid tumors: the evidence to date. Oncotargets Ther. 2015;8:3691–3701. doi: 10.2147/OTT.S78805.
    1. Boehringer Ingelheim OFEV (nintedanib*) approved in the EU for the treatment of IPF. . Accessed 30 Oct 2017
    1. Du Bois A, Kristensen G, Ray-Coquard I, Reuss A, Pignata S, Colombo N, Denison U, Vergote I, Del Campo JM, Ottevanger P, Heubner M, Minarik T, Sevin E, de Gregorio N, Bidziński M, Pfisterer J, Malander S, Hilpert F, Mirza MR, Scambia G, Meier W, Nicoletto MO, Bjorge L, Lortholary A, Sailer MO, Merger M, Harter P, Consortium ASGlGCIENoGOTGI. 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. 2016;17(1):78–89. doi: 10.1016/S1470-2045(15)00366-6.
    1. Elit L, Hirte H. Palliative systemic therapy for women with recurrent epithelial ovarian cancer: current options. Oncotargets Ther. 2013
    1. Ferron G, De Rauglaudre G, Ray-Coquard IL, Lesoin A, Joly F, Lortholary A, Raban N, Peron J, Malaurie-Agostini E, Gouy S, Kaminsky MC, Meunier J, Alexandre J, Berton-Rigaud D, Coussy F, Favier L, Venat-Bouvet L, Marmion F, Combe P, Pujade-Lauraine E. The CHIVA study: a GINECO randomized double blind phase II trial of nintedanib versus placebo with the neo-adjuvant chemotherapy (NACT) strategy for patients (pts) with advanced unresectable ovarian cancer (OC). Report of the interval debulking surgery (IDS) safety outcome. Ann Oncol. 2016
    1. Clinical.Trials.METRO-BIBF. . Accessed 30 Oct 2017
    1. Clinical.Trials.BIBF1120. . Accessed 30 Oct 2017
    1. Karlan BY, Oza AM, Richardson GE, Provencher DM, Hansen VL, Buck M, Chambers SK, Ghatage P, Pippitt CH, Brown JV, Covens A, Nagarkar RV, Davy M, Leath CA, Nguyen H, Stepan DE, Weinreich DM, Tassoudji M, Sun YN, Vergote IB. Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer. J Clin Oncol. 2012;30(4):362–371. doi: 10.1200/JCO.2010.34.3178.
    1. Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhomme C, Richardson G, Rincon DG, Coleman RL, Herzog TJ, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Tassoudji M, Navale L, Warner DJ, Oza AM. 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(8):799–808. doi: 10.1016/S1470-2045(14)70244-X.
    1. Yap TA, Sandhu SK, Carden CP, de Bono JS. Poly(ADP-ribose) polymerase (PARP) inhibitors: exploiting a synthetic lethal strategy in the clinic. CA Cancer J Clin. 2011;61(1):31–49. doi: 10.3322/caac.20095.
    1. Kluzek K, Białkowska A, Koczorowska A, Zdzienicka MZ. Inhibitory polimerazy poli(ADP-rybozy) (PARP) w terapii nowotworów z mutacjami BRCA1/2. Advances in hygiene and experimental medicine. Postepy Hig Med Dosw. 2012;66:13. doi: 10.5604/17322693.1000548.
    1. Murata S, Zhang C, Finch N, Zhang K, Campo L, Breuer EK. Predictors and modulators of synthetic lethality: an update on PARP inhibitors and personalized medicine. Biomed Res Int. 2016
    1. FDA. Olaparib. Approvement. . Accessed 30 Oct 2017
    1. SOLO2. Trial. . Accessed 30 Oct 2017
    1. Liu JF, Konstantinopoulos PA, Matulonis UA. PARP inhibitors in ovarian cancer: current status and future promise. Gynecol Oncol. 2014;133(2):362–369. doi: 10.1016/j.ygyno.2014.02.039.
    1. McLachlan J, George A, Banerjee S. The current status of PARP inhibitors in ovarian cancer. Tumori. 2016;102(5):433–440. doi: 10.5301/tj.5000558.
    1. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Dougherty B, Orr M, Hodgson D, Barrett JC, Matulonis U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014;15(8):852–861. doi: 10.1016/S1470-2045(14)70228-1.
    1. Pujade-Lauraine E, Ledermann JA, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N. Treatment with olaparib monotherapy in the maintenance setting significantly improves progression-free survival in patients with platinum sensitive relapsed ovarian cancer: results from the phase III SOLO2 study. Gynecol Oncol. 2017;145:220. doi: 10.1016/j.ygyno.2017.03.505.
    1. Matulonis UA, Penson RT, Domchek SM, Kaufman B, Shapira-Frommer R, Audeh MW, Kaye S, Molife LR, Gelmon KA, Robertson JD, Mann H, Ho TW, Coleman RL. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol. 2016;27(6):1013–1019. doi: 10.1093/annonc/mdw133.
    1. Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RHJ, Sonke GS, Colombo N, Spacek J, Vuylsteke P, Hirte H, Mahner S, Plante M, Schmalfeldt B, Mackay H, Rowbottom J, Lowe ES, Dougherty B, Barrett JC, Friedlander M. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol. 2015;16(1):87–97. doi: 10.1016/S1470-2045(14)71135-0.
    1. Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel BJ, Buss MK, Nattam S, Hurteau J, Luo WX, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014;15(11):1207–1214. doi: 10.1016/S1470-2045(14)70391-2.
    1. Matulonis UA, Wulf G, Barry W, Birrer M, Westin S, Spagnoletti T, Bell-McGuinn K, Obermayer E, Whalen C, Aghajanian C, Solit D, Mills G, Cantley L, Winer E. Phase I of oral BKM120 or BYL719 and olaparib for high-grade serous ovarian cancer or triple-negative breast cancer: final results of the BKM120 plus olaparib cohort. Cancer Res. 2015
    1. Michalarea V, Lorente D, Lopez J, Carreira S, Hassam H, Parmar M, Sathiyayogan N, Turner A, Hall E, Fandos SS, Seeramreddi S, Decordova S, Swales K, Ruddle R, Raynaud F, Tunariu N, Attard G, Molife LR, Banerji U, Plummer R, de Bono JS, Yap TA. Accelerated phase I trial of two schedules of the combination of the PARP inhibitor olaparib and AKT inhibitor AZD5363 using a novel intrapatient dose escalation design in advanced cancer patients. Cancer Res. 2015
    1. Scott LJ. Niraparib: first global approval. Drugs. 2017;77(9):1029–1034. doi: 10.1007/s40265-017-0752-y.
    1. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Madry R, Christensen RD, Berek JS, Dorum A, Tinker AV, du Bois A, Gonzalez-Martin A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA, Investigators E-ON. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154–2164. doi: 10.1056/NEJMoa1611310.
    1. Syed YY. Rucaparib: first global approval. Drugs. 2017;77(5):585–592. doi: 10.1007/s40265-017-0716-2.
    1. FDA. Rucaparib. Approvement. . Accessed 30 Oct 2017
    1. Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O’Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017;18(1):75–87. doi: 10.1016/S1470-2045(16)30559-9.
    1. ESMO2017. Rucaparib . ESMO 2017 press release: rucaparib boosts progression-free survival in BRCA mutant recurrent ovarian cancer. Lugano, Madrid: ESMO; 2017.
    1. Papa A, Caruso D, Strudel M, Tomao S, Tomao F. Update on Poly-ADP-ribose polymerase inhibition for ovarian cancer treatment. J Transl Med. 2016;14:267. doi: 10.1186/s12967-016-1027-1.
    1. Ledermann JA, Drew Y, Kristeleit RS. Homologous recombination deficiency and ovarian cancer. Eur J Cancer. 2016;60:49–58. doi: 10.1016/j.ejca.2016.03.005.
    1. Banerjee S (2016) Identifying ovarian cancer patients for PARP inhibitor therapy. In: Oral presentation at 16th Biennial Meeting of the international gynecologic cancer society, Lisbon
    1. Tappenden P, Harnan S, Ren S, Thokala P, Wong R, Mukuria C, Green C, Pledge S, Tidy J. Olaparib for maintenance treatment of BRCA 1 or 2 mutated, relapsed, platinum-sensitive ovarian, fallopian tube and peritoneal cancer in people whose relapsed disease has responded to platinum-based chemotherapy: an evidence review group perspective of a NICE single technology appraisal. PharmacoEconomics. 2017;35(1):12. doi: 10.1007/s40273-016-0440-x.
    1. Wolford JE, Bai JR, Eskander RH, Keller R, Minion LE, Chan JK, Monk BJ, Tewari KS. Evaluating the cost-effectiveness of current FDA-approved PARP inhibitors for the treatment of recurrent ovarian cancer. J Clin Oncol. 2017
    1. Cheung A, Bax HJ, Josephs DH, Ilieva KM, Pellizzari G, Opzoomer J, Bloomfield J, Fittall M, Grigoriadis A, Figini M, Canevari S, Spicer JF, Tutt AN, Karagiannis SN. Targeting folate receptor alpha for cancer treatment. Oncotarget. 2016;7(32):52553–52574. doi: 10.18632/oncotarget.9651.
    1. Drerup JM, Liu Y, Padron AS, Murthy K, Hurez V, Zhang B, Curiel TJ. Immunotherapy for ovarian cancer. Curr Treat Options Oncol. 2015;16(1):1. doi: 10.1007/s11864-014-0317-1.
    1. Lutz RJ. Targeting the folate receptor for the treatment of ovarian cancer. Transl Cancer Res. 2015;4(1):118–126.
    1. Bergamini A, Ferrero S, Maggiore ULR, Scala C, Pella F, Vellone VG, Petrone M, Rabaiotti E, Cioffi R, Candiani M, Mangili G. Folate receptor alpha antagonists in preclinical and early stage clinical development for the treatment of epithelial ovarian cancer. Expert Opin Investig Drugs. 2016;25(12):1405–1412. doi: 10.1080/13543784.2016.1254616.
    1. Sato S, Itamochi H. Profile of farletuzumab and its potential in the treatment of solid tumors. Oncotargets Ther. 2016;9:1181–1188. doi: 10.2147/OTT.S98242.
    1. Armstrong DK, White AJ, Weil SC, Phillips M, Coleman RL. Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer. Gynecol Oncol. 2013;129(3):452–458. doi: 10.1016/j.ygyno.2013.03.002.
    1. Ledermann JA, Canevari S, Thigpen T. Targeting the folate receptor: diagnostic and therapeutic approaches to personalize cancer treatments. Ann Oncol. 2015;26(10):2034–2043. doi: 10.1093/annonc/mdv250.
    1. Clinical. Trials. Vintafolide. EC-FV-02. Trial. . Accessed 30 Oct 2017
    1. Vergote IB, Marth C, Coleman RL. Role of the folate receptor in ovarian cancer treatment: evidence, mechanism, and clinical implications. Cancer Metastasis Rev. 2015;34(1):41–52. doi: 10.1007/s10555-014-9539-8.
    1. Lluesma SM, Wolfer A, Harari A, Kandalaft LE. Cancer vaccines in ovarian cancer. How can we improve? Biomedicines. 2016;4(2):28.
    1. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348(3):203–213. doi: 10.1056/NEJMoa020177.
    1. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, Kepner J, Odunsi T, Ritter G, Lele S, Chen YT, Ohtani H, Old LJ, Odunsi K. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 2005;102(51):18538–18543. doi: 10.1073/pnas.0509182102.
    1. Chester C, Dorigo O, Berek JS, Kohrt H. Immunotherapeutic approaches to ovarian cancer treatment. J Immunother Cancer. 2015;3:7. doi: 10.1186/s40425-015-0051-7.
    1. Gaillard SL, Secord AA, Monk B. The role of immune checkpoint inhibition in the treatment of ovarian cancer. Gynecol Oncol Res Pract. 2016;3(11):14.
    1. Krishnan V, Berek JS, Dorigo O. Immunotherapy in ovarian cancer. Curr Probl Cancer. 2017;41(1):48–63. doi: 10.1016/j.currproblcancer.2016.11.003.
    1. Alipour S, Zoghi S, Khalili N, Hirbod-Mobarakeh A, Emens LA, Rezaei N. Specific immunotherapy in ovarian cancer: a systematic review. Immunotherapy. 2016;8(10):1193–1204. doi: 10.2217/imt-2016-0034.
    1. Iwai Y, Hamanishi J, Chamoto K, Honjo T. Cancer immunotherapies targeting the PD-1 signaling pathway. J Biomed Sci. 2017;24:26. doi: 10.1186/s12929-017-0329-9.
    1. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450–461. doi: 10.1016/j.ccell.2015.03.001.
    1. Pfisterer J, du Bois A, Sehouli J, Loibl S, Reinartz S, Reuss A, Canzler U, Belau A, Jackisch C, Kimmig R, Wollschlaeger K, Heilmann V, Hilpert F. The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann Oncol. 2006;17(10):1568–1577. doi: 10.1093/annonc/mdl357.
    1. Sabbatini P, Dupont J, Aghajanian C, Derosa F, Poynor E, Anderson S, Hensley M, Livingston P, Iasonos A, Spriggs D, McGuire W, Reinartz S, Schneider S, Grande C, Lele S, Rodabaugh K, Kepner J, Ferrone S, Odunsi K. Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Clin Cancer Res. 2006;12(18):5503–5510. doi: 10.1158/1078-0432.CCR-05-2670.
    1. Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB, Wang XY. Therapeutic cancer vaccines: past, present, and future. Adv Cancer Res. 2013;119:421–475. doi: 10.1016/B978-0-12-407190-2.00007-1.
    1. Gray HJ, Benigno B, Berek J, Chang J, Mason J, Mileshkin L, Mitchell P, Moradi M, Recio FO, Michener CM, Secord AA, Tchabo NE, Chan JK, Young J, Kohrt H, Gargosky SE, Goh JC. Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial. J Immunother Cancer. 2016;4:34. doi: 10.1186/s40425-016-0137-x.
    1. Karbach J, Neumann A, Brand K, Wahle C, Siegel E, Maeurer M, Ritter E, Tsuji T, Gnjatic S, Old LJ, Ritter G, Jager E. Phase I clinical trial of mixed bacterial vaccine (coley’s toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity. Clin Cancer Res. 2012;18(19):5449–5459. doi: 10.1158/1078-0432.CCR-12-1116.
    1. Sabbatini P, Harter P, Scambia G, Sehouli J, Meier W, Wimberger P, Baumann KH, Kurzeder C, Schmalfeldt B, Cibula D, Bidzinski M, Casado A, Martoni A, Colombo N, Holloway RW, Selvaggi L, Li A, del Campo J, Cwiertka K, Pinter T, Vermorken JB, Pujade-Lauraine E, Scartoni S, Bertolotti M, Simonelli C, Capriati A, Maggi CA, Berek JS, Pfisterer J. Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO-The MIMOSA Study. J Clin Oncol. 2013;31(12):1554–1561. doi: 10.1200/JCO.2012.46.4057.
    1. Mantia-Smaldone GM, Corr B, Chu CS. Immunotherapy in ovarian cancer. Hum Vaccin Immunother. 2012;8(9):1179–1191. doi: 10.4161/hv.20738.
    1. Smolle E, Taucher V, Haybaeck J. Malignant ascites in ovarian cancer and the role of targeted therapeutics. Anticancer Res. 2014;34(4):1553–1561.
    1. Morano WF, Aggarwal A, Love P, Richard SD, Esquivel J, Bowne WB. Intraperitoneal immunotherapy: historical perspectives and modern therapy. Cancer Gene Ther. 2016;23(11):373–381. doi: 10.1038/cgt.2016.49.
    1. Ruf P, Kluge M, Jager M, Burges A, Volovat C, Heiss MM, Hess J, Wimberger P, Brandt B, Lindhofer H. Pharmacokinetics, immunogenicity and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patients. Br J Clin Pharmacol. 2010;69(6):617–625. doi: 10.1111/j.1365-2125.2010.03635.x.
    1. Seimetz D. Novel monoclonal antibodies for cancer treatment: the trifunctional antibody catumaxomab [removab (R)] J Cancer. 2011;2:309–316. doi: 10.7150/jca.2.309.
    1. Berek JS, Edwards RP, Parker LP, DeMars LR, Herzog TJ, Lentz SS, Morris RT, Akerley WL, Holloway RW, Method MW, Plaxe SC, Walker JL, Friccius-Quecke H, Krasner CN. Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer a phase II study. Int J Gynecol Cancer. 2014;24(9):1583–1589. doi: 10.1097/IGC.0000000000000286.
    1. Heiss MM, Murawa P, Koralewski P, Kutarska E, Kolesnik OO, Ivanchenko VV, Dudnichenko AS, Aleknaviciene B, Razbadauskas A, Gore M, Ganea-Motan E, Ciuleanu T, Wimberger P, Schmittel A, Schmalfeldt B, Burges A, Bokemeyer C, Lindhofer H, Lahr A, Parsons SL. The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer. 2010;127(9):2209–2221. doi: 10.1002/ijc.25423.
    1. Seeber A, Braicu I, Untergasser G, Nassir M, Fong D, Botta L, Gastl G, Fiegl H, Zeimet A, Sehouli J, Spizzo G. Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab. Oncotarget. 2015;6(28):25017–25023. doi: 10.18632/oncotarget.4496.
    1. Fossati M, Buzzonetti A, Monego G, Catzola V, Scambia G, Fattorossi A, Battaglia A. Immunological changes in the ascites of cancer patients after intraperitoneal administration of the bispecific antibody catumaxomab (anti-EpCAM x anti-CD3) Gynecol Oncol. 2015;138(2):343–351. doi: 10.1016/j.ygyno.2015.06.003.
    1. Baumann K, Pfisterer J, Wimberger P, Burchardi N, Kurzeder C, du Bois A, Loibl S, Sehouli J, Huober J, Schmalfeldt B, Vergote I, Luck HJ, Wagner U. Intraperitoneal treatment with the trifunctional bispecific antibody catumaxomab in patients with platinum-resistant epithelial ovarian cancer: a phase IIa study of the AGO Study Group. Gynecol Oncol. 2011;123(1):27–32. doi: 10.1016/j.ygyno.2011.06.004.
    1. Burges A, Wimberger P, Kumper C, Gorbounova V, Sommer H, Schmalfeldt B, Pfisterer J, Lichinitser M, Makhson A, Moiseyenko V, Lahr A, Schulze E, Jager M, Strohlein MA, Heiss MM, Gottwald T, Lindhofer H, Kimmig R. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007;13(13):3899–3905. doi: 10.1158/1078-0432.CCR-06-2769.
    1. Borlak J, Langer F, Spanel R, Schondorfer G, Dittrich C. Immune-mediated liver injury of the cancer therapeutic antibody catumaxomab targeting EpCAM, CD3 and Fc gamma receptors. Oncotarget. 2016;7(19):28059–28074. doi: 10.18632/oncotarget.8574.
    1. Gotlieb WH, Amant F, Advani S, Goswami C, Hirte H, Provencher D, Somani N, Yamada SD, Tamby JF, Vergote I. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol. 2012;13(2):154–162. doi: 10.1016/S1470-2045(11)70338-2.
    1. Colombo N, Mangili G, Mammoliti S, Kalling M, Tholander B, Sternas L, Buzenet G, Chamberlain D. A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites. Gynecol Oncol. 2012;125(1):42–47. doi: 10.1016/j.ygyno.2011.11.021.
    1. Tagawa T, Morgan R, Yen Y, Mortimer J. Ovarian cancer: opportunity for targeted therapy. J Oncol. 2012;2012:682480. doi: 10.1155/2012/682480.

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