Download PDF
Frauenheilkunde up2date 2021; 15(02): 143-162
DOI: 10.1055/a-1068-7227
Gynäkologische Onkologie

Medikamentöse Therapie des Ovarialkarzinoms

Frederik Marmé
› Further Information
Also available at
    Permissions and Reprints All articles of this category

PARP-Inhibitoren und prädiktive Biomarker sowie die HRD-Testung haben in den letzten Jahren Einzug in die Diagnostik und Therapie bei allen Stadien des Ovarialkarzinoms gefunden. Dieser Beitrag beleuchtet die klinische und therapeutische Evidenz und gibt das erforderliche Hintergrundwissen für die Behandlung aller Stadien des Ovarialkarzinoms.
Kernaussagen

  • Für die richtige Therapieentscheidung in der Erstlinie ist beim frühen Ovarialkarzinom auf jeden Fall ein komplettes operatives Staging erforderlich.

  • Der heutige Standard für die Erstlinientherapie des fortgeschrittenen Ovarialkarzinoms besteht aus 6 Zyklen Carboplatin (AUC 5) und Paclitaxel (175 mg/m2) in 3-wöchentlichen Gaben.

  • In der Erstlinientherapie mit Carboplatin/Paclitaxel sollten aufgrund der Evidenz keine Änderungen bei Dosisdichte und Intensität erfolgen.

  • Die Erstlinienbehandlung mit Bevacizumab führt zu einer signifikanten Verlängerung des progressionsfreien Überlebens ohne Einfluss auf das Gesamtüberleben. Lediglich in Subgruppen mit besonders hohem Risiko für frühe Rezidive deutet sich ein Vorteil im Gesamtüberleben an.

  • Bei Patientinnen mit BRCA-Mutationsnachweis oder einer HRD sind PARP-Inhibitoren als Erhaltungstherapie nach Ansprechen auf die platinhaltige Erstlinienchemotherapie der Standard.

  • Für Patientinnen mit BRCA-Mutation oder HRD können auch beide Therapieprinzipien (Antiangiogenese und PARP-Inhibition) in der Erstlinientherapie kombiniert werden.

  • Für Patientinnen ohne Nachweis einer HRD sind sowohl eine Erstlinientherapie mit Bevacizumab als auch die PARPi-Erhaltungstherapie mit Niraparib valide Therapieoptionen.

  • Für eine bestmögliche Therapie in der Erstlinie ist eine BRCA- und HRD-Testung erforderlich.

  • Im platin-geeigneten Rezidiv sind platinhaltige Kombinationschemotherapien einer Monotherapie mit Platin und platinfreien Alternativen überlegen.

  • Im platingeeigneten Rezidiv eines High-grade Karzinoms ist bei Ansprechen auf eine platinhaltige Therapie die PARPi-Erhaltungstherapie der Standard.

  • Platinfreie Therapieoptionen sind im platingeeigneten Rezidiv der platinhaltigen Therapie unterlegen.

  • Der Nutzen ist für Patientinnen mit nachgewiesener Mutation oder HRD am größten.

  • Therapie der Wahl im platinungeeigneten Rezidiv ist eine Monochemotherapie mit z.B Paclitaxel, pegyliertem liposomalem Doxorubicin oder Topotecan. Die Chemotherapie kann ggf. mit Bevacizumab kombiniert werden.

Schlüsselwörter

Ovarialkarzinom - Evidenz - Chemotherapie - Bevacizumab - PARP-Inhibitor - BRCA - HRD


Publication History

Article published online:
07 April 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Trimbos JB, Parmar M, Vergote I. et al. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst 2003; 95: 105-112
    CrossrefPubMedGoogle Scholar
  • 2 Colombo N, Guthrie D, Chiari S. et al. International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst 2003; 95: 125-132
    CrossrefPubMedGoogle Scholar
  • 3 Collinson F, Qian W, Fossati R. et al. Optimal treatment of early-stage ovarian cancer. Ann Oncol 2014; 25: 1165-1171
    CrossrefPubMedGoogle Scholar
  • 4 Chan JK, Tian C, Fleming GF. et al. The potential benefit of 6 vs. 3 cycles of chemotherapy in subsets of women with early-stage high-risk epithelial ovarian cancer: an exploratory analysis of a Gynecologic Oncology Group study. Gynecol Oncol 2010; 116: 301-306
    CrossrefPubMedGoogle Scholar
  • 5 Bell J, Brady MF, Young RC. et al. Randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in early stage epithelial ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2006; 102: 432-439
    CrossrefPubMedGoogle Scholar
  • 6 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): S3-Leitlinie Diagnostik, Therapie und Nachsorge maligner Ovarialtumoren, Langversion 4.0. 2020. AWMF-Registernummer: 032/035OL. Im Internet (Stand: 02/2021): https://www.leitlinienprogramm-onkologie.de/leitlinien/ovarialkarzinom/
    Google Scholar
  • 7 Colombo N, Sessa C, du Bois A. et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent diseasedagger. Ann Oncol 2019; 30: 672-705
    CrossrefPubMedGoogle Scholar
  • 8 du Bois A, Luck HJ, Meier W. et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003; 95: 1320-1329
    CrossrefPubMedGoogle Scholar
  • 9 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 2003; 21: 3194-3200
    CrossrefPubMedGoogle Scholar
  • 10 Vasey PA, Jayson GC, Gordon A. et al. 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
    CrossrefPubMedGoogle Scholar
  • 11 Markman M, Liu PY, Moon J. et al. Impact on survival of 12 versus 3 monthly cycles of paclitaxel (175 mg/m2) administered to patients with advanced ovarian cancer who attained a complete response to primary platinum-paclitaxel: follow-up of a Southwest Oncology Group and Gynecologic Oncology Group phase 3 trial. Gynecol Oncol 2009; 114: 195-198
    CrossrefPubMedGoogle Scholar
  • 12 Katsumata N, Yasuda M, Isonishi S. et al. 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
    CrossrefPubMedGoogle Scholar
  • 13 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 2014; 15: 396-405
    CrossrefPubMedGoogle Scholar
  • 14 Chan JK, Brady MF, Penson RT. et al. Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer. N Engl J Med 2016; 374: 738-748
    CrossrefPubMedGoogle Scholar
  • 15 Clamp AR, James EC, McNeish IA. et al. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial. Lancet 2019; 394: 2084-2095
    CrossrefPubMedGoogle Scholar
  • 16 Armstrong DK, Bundy B, Wenzel L. et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006; 354: 34-43
    CrossrefPubMedGoogle Scholar
  • 17 Alberts DS, Liu PY, Hannigan EV. et al. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 1996; 335: 1950-1955
    CrossrefPubMedGoogle Scholar
  • 18 Markman M, Bundy BN, Alberts DS. et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol 2001; 19: 1001-1007
    CrossrefPubMedGoogle Scholar
  • 19 Walker JL, Brady MF, Wenzel L. et al. Randomized trial of intravenous versus intraperitoneal chemotherapy plus bevacizumab in advanced ovarian carcinoma: an NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol 2019; 37: 1380-1390
    CrossrefPubMedGoogle Scholar
  • 20 Spiliotis J, Halkia E, Lianos E. et al. Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Ann Surg Oncol 2015; 22: 1570-1575
    CrossrefPubMedGoogle Scholar
  • 21 van Driel WJ, Koole SN, Sikorska K. et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med 2018; 378: 230-240
    CrossrefPubMedGoogle Scholar
  • 22 Lim MC, Chang S-J, Yoo HJ. et al. Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer. J Clin Oncol 2017; 35: 5520-5520
    CrossrefGoogle Scholar
  • 23 Colombo N, Sessa C, du Bois A. et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Ann Oncol 2019; 30: 672-705
    CrossrefPubMedGoogle Scholar
  • 24 Tewari KS, Burger RA, Enserro D. et al. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol 2019; 37: 2317-2328
    CrossrefPubMedGoogle Scholar
  • 25 Burger RA, Brady MF, Bookman MA. et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365: 2473-2483
    CrossrefPubMedGoogle Scholar
  • 26 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 2015; 16: 928-936
    CrossrefPubMedGoogle Scholar
  • 27 Perren TJ, Swart AM, Pfisterer J. et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011; 365: 2484-2496
    CrossrefPubMedGoogle Scholar
  • 28 Harter P, Hilpert F, Sehouli J. et al. Therapiequalität des fortgeschrittenen Ovarialkarzinoms in Deutschland. Der Frauenarzt 2020; 61: 182-188
    Google Scholar
  • 29 Marchetti C, Muzii L, Romito A, Benedetti Panici P. First-line treatment of women with advanced ovarian cancer: focus on bevacizumab. Onco Targets Ther 2019; 12: 1095-1103
    CrossrefPubMedGoogle Scholar
  • 30 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 2017; 70: 133-142
    CrossrefPubMedGoogle Scholar
  • 31 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: 256-259
    CrossrefPubMedGoogle Scholar
  • 32 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 2018; 36: 5506
    CrossrefGoogle Scholar
  • 33 Hauke J, Hahnen E, Schneider S. et al. Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883). J Med Genet 2019; 56: 574-580
    CrossrefPubMedGoogle Scholar
  • 34 Harter P, Hauke J, Heitz F. et al. Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1). PLoS One 2017; 12: e0186043
    CrossrefPubMedGoogle Scholar
  • 35 Moore KN, Secord AA, Geller MA. et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2019; 20: 636-648
    CrossrefPubMedGoogle Scholar
  • 36 Gonzalez-Martin A, Pothuri B, Vergote I. et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2019; 381: 2391-2402
    CrossrefPubMedGoogle Scholar
  • 37 Swisher EM, Lin KK, Oza AM. et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol 2017; 18: 75-87
    CrossrefPubMedGoogle Scholar
  • 38 Coleman RL, Oza AM, Lorusso D. et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 390: 1949-1960
    CrossrefPubMedGoogle Scholar
  • 39 Mirza MR, Monk BJ, Herrstedt J. et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 2016; 375: 2154-2164
    CrossrefPubMedGoogle Scholar
  • 40 Banerjee S, Moore KN, Colombo N. et al. 811MO Maintenance olaparib for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1. Ann Oncol 2020; 31: S613
    CrossrefGoogle Scholar
  • 41 Moore K, Colombo N, Scambia G. et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 2018; 379: 2495-2505
    CrossrefPubMedGoogle Scholar
  • 42 Du Bois A, Sehouli J, Vergote I. et al. Randomized phase III study to evaluate the impact of secondary cytoreductive surgery in recurrent ovarian cancer: Final analysis of AGO DESKTOP III/ENGOT-ov20. J Clin Oncol 2020; 38: 6000
    CrossrefGoogle Scholar
  • 43 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 2003; 361: 2099-2106
    CrossrefPubMedGoogle Scholar
  • 44 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 2006; 24: 4699-4707
    CrossrefPubMedGoogle Scholar
  • 45 Wagner U, Marth C, Largillier R. et al. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs. paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer 2012; 107: 588-591
    CrossrefPubMedGoogle Scholar
  • 46 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 2010; 28: 3323-3329
    CrossrefPubMedGoogle Scholar
  • 47 Pfisterer J, Shannon CM, Baumann K. et al. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol 2020; 21: 699-709
    CrossrefPubMedGoogle Scholar
  • 48 Monk BJ, Herzog TJ, Kaye SB. et al. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol 2010; 28: 3107-3114
    CrossrefPubMedGoogle Scholar
  • 49 Poveda A, Vergote I, Tjulandin S. et al. Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer: outcomes in the partially platinum-sensitive (platinum-free interval 6–12 months) subpopulation of OVA-301 phase III randomized trial. Ann Oncol 2011; 22: 39-48
    CrossrefPubMedGoogle Scholar
  • 50 Pignata S, Scambia G, Bologna A. et al. Randomized Controlled Trial Testing the Efficacy of Platinum-Free Interval Prolongation in Advanced Ovarian Cancer: The MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG Study. J Clin Oncol 2017; 35: 3347-3353
    CrossrefPubMedGoogle Scholar
  • 51 Colombo N, Gadducci A, Sehouli J. et al. LBA30 INOVATYON study: Randomized phase III international study comparing trabectedin/PLD followed by platinum at progression vs. carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6–12 months after last platinum line. Ann Oncol 2020; 31: S1161
    CrossrefGoogle Scholar
  • 52 Aghajanian C, Goff B, Nycum LR. et al. 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: 10-16
    CrossrefPubMedGoogle Scholar
  • 53 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 2012; 30: 2039-2045
    CrossrefPubMedGoogle Scholar
  • 54 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 2017; 18: 779-791
    CrossrefPubMedGoogle Scholar
  • 55 Pfisterer J, Dean AP, Baumann K. 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, SGCTG). Ann Oncol 2018; 29: mdy285.142-mdy285.142
    CrossrefGoogle Scholar
  • 56 Pfisterer J, Shannon CM, Baumann K. et al. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol 2020; 21: 699-709
    CrossrefPubMedGoogle Scholar
  • 57 Audeh MW, Carmichael J, Penson RT. et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 2010; 376: 245-251
    CrossrefPubMedGoogle Scholar
  • 58 Gelmon KA, Tischkowitz M, Mackay H. et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncology 2011; 12: 852-861
    CrossrefPubMedGoogle Scholar
  • 59 Kaufman B, Shapira-Frommer R, Schmutzler RK. et al. Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. J Clin Oncol 2015; 33: 244-250
    CrossrefPubMedGoogle Scholar
  • 60 Ledermann J, Harter P, Gourley C. et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012; 366: 1382-1392
    CrossrefPubMedGoogle Scholar
  • 61 Ledermann J, Harter P, Gourley C. et al. 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: 852-861
    CrossrefPubMedGoogle Scholar
  • 62 Pujade-Lauraine E, Ledermann JA, Selle F. et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2017; 18: 1274-1284
    CrossrefPubMedGoogle Scholar
  • 63 Coleman RL, Oza AM, Lorusso D. et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 390: 1949-1961
    CrossrefPubMedGoogle Scholar
  • 64 Lihua P, Chen XY, Wu TX. Topotecan for ovarian cancer. Cochrane Database Syst Rev 2008; (02) CD005589
    PubMedGoogle Scholar
  • 65 Ezcurdia L, Jovtis SL, Mickiewicz E. et al. Paclitaxel in platinum-resistant ovarian cancer patients. Argentine Multicenter Taxol Group. Semin Oncol 1997; 24: S15-53-S15-56
    Google Scholar
  • 66 Gore ME, Levy V, Rustin G. et al. Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer 1995; 72: 1016-1019
    CrossrefPubMedGoogle Scholar
  • 67 Seewaldt VL, Greer BE, Cain JM. et al. Paclitaxel (Taxol) treatment for refractory ovarian cancer: phase II clinical trial. Am J Obstet Gynecol 1994; 170: 1666-1670 discussion 1670–1661
    CrossrefPubMedGoogle Scholar
  • 68 Gynecologic Oncology Group. Markman M, Blessing J. et al. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol 2006; 101: 436-440
    CrossrefPubMedGoogle Scholar
  • 69 Gordon AN, Fleagle JT, Guthrie D. et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 2001; 19: 3312-3322
    CrossrefPubMedGoogle Scholar
  • 70 Markman M, Kennedy A, Webster K. et al. Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol Oncol 2000; 78: 369-372
    CrossrefPubMedGoogle Scholar
  • 71 Mutch DG, Orlando M, Goss T. et al. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol 2007; 25: 2811-2818
    CrossrefPubMedGoogle Scholar
  • 72 Sehouli J, Stengel D, Harter P. et al. Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol 2011; 29: 242-248
    CrossrefPubMedGoogle Scholar
  • 73 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft DK, AWMF). S3-Leitlinie Diagnostik, Therapie und Nachsorge maligner Ovarialtumoren, 2017. Im Internet (Stand: 11/2017): http://leitlinienprogramm-onkologie.de/Ovarialkarzinom.61.0.html
    Google Scholar
  • 74 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 2014; 32: 1309-1316
    CrossrefPubMedGoogle Scholar
  • 75 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 2014; 32: 1302-1308
    CrossrefPubMedGoogle Scholar
  • 76 Zamarin D, Burger RA, Sill MW. et al. Randomized Phase II Trial of Nivolumab Versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study. J Clin Oncol 2020; 38: 1814-1823
    CrossrefPubMedGoogle Scholar
  • 77 Moore KN, Martin LP, OʼMalley DM. et al. Safety and activity of mirvetuximab soravtansine (IMGN853), a folate receptor alpha-targeting antibody-drug conjugate, in platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: A phase I expansion study. J Clin Oncol 2017; 35: 1112-1118
    CrossrefPubMedGoogle Scholar
  • 78 Moore K, Oza A, Colombo N. et al. 992O – FORWARD I (GOG 3011): A phase III study of mirvetuximab soravtansine, a folate receptor alpha (FRa)-targeting antibody-drug conjugate (ADC), versus chemotherapy in patients (pts) with platinum-resistant ovarian cancer (PROC). Ann Oncol 2019; 30: v403
    CrossrefGoogle Scholar