Treatment of Recurrent Epithelial Ovarian Cancer

Abstract

Epithelial ovarian cancer is the most common cause of death from gynecological tumors. Most patients with advanced ovarian cancer develop recurrence after concluding first-line therapy, making further lines of therapy necessary. The choice of therapy depends on various criteria such as tumor biology, the patientʼs general condition (ECOG), toxicity, previous chemotherapy, and response to chemotherapy. The platinum-free or treatment-free interval determines the potential response to repeat platinum-based therapy. If patients have late recurrence, i.e. > 6 months after the end of the last platinum-based therapy (i.e., they were previously platinum-sensitive), then they are usually considered suitable for another round of a platinum-based combination therapy. Patients who are not considered suitable for platinum-based chemotherapy are treated with a platinum-free regimen such as weekly paclitaxel, pegylated liposomal doxorubicin (PLD), gemcitabine, or topotecan. Treatment for the patient subgroup which is considered suitable for platinum-based therapy but cannot receive carboplatin due to uncontrollable hypersensitivity reactions may consist of trabectedin and PLD. While the use of surgery to treat recurrence has long been a controversial issue, new findings from the DESKTOP III study of the AGO working group have drawn attention to this issue again, particularly for patients with a platinum-free interval of > 6 months and a positive AGO score. Clinical studies have also shown the efficacy of angiogenesis inhibitors such as bevacizumab and the PARP inhibitors olaparib, niraparib and rucaparib. These drugs have substantially changed current treatment practice and expanded the range of available therapies. It is important to differentiate between purely maintenance therapy after completing CTX, continuous maintenance therapy during CTX, and the therapeutic use of these substances. The PARP inhibitors niraparib, olaparib and rucaparib have already been approved for use by the FDA and the EMA. The presence of a BRCA mutation is a predictive factor for a better response to PARP inhibitors.

Key words

recurrent ovarian cancer - ROC - surgery for recurrence - PARP inhibitor - anti-angiogenesis

Publikationsverlauf

Eingereicht: 06. Juli 2020

Angenommen nach Revision: 26. Oktober 2020

Artikel online veröffentlicht:
03. Dezember 2020

• References/Literatur

• 1 Torre LA, Trabert B, DeSantis CE. et al. Ovarian cancer statistics, 2018. CA Cancer J Clin 2018; 68: 284-296 doi:10.3322/caac.21456
• 2 Wilson MK, Pujade-Lauraine E, Aoki D. et al. Fifth ovarian cancer consensus conference of the gynecologic cancer intergroup: Recurrent disease. Ann Oncol 2017; 28: 727-732 doi:10.1093/annonc/mdw663
• 3 du Bois A, Reuss A, Pujade-Lauraine E. et al. 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 2009; 115: 1234-1244 doi:10.1002/cncr.24149
• 4 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 doi:10.1016/S0140-6736(03)13718-X
• 5 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. Int J Gynecol Cancer 2019; 29: 728-760 doi:10.1136/ijgc-2019-000308
• 6 McGee J, Bookman M, Harter P. et al. Fifth ovarian cancer consensus conference: Individualized therapy and patient factors. Ann Oncol 2017; 28: 702-710 doi:10.1093/annonc/mdx010
• 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 disease. Int J Gynecol Cancer 2019; 29: 728-760 doi:10.1136/ijgc-2019-000308
• 8 Friedlander ML. Do all patients with recurrent ovarian cancer need systemic therapy?. Cancer 2019; 125 (S24): 4602-4608 doi:10.1002/cncr.32476
• 9 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 (15_suppl):: 6000 doi:10.1200/JCO.2020.38.15_suppl.6000
• 10 Harter P, Sehouli J, Reuss A. et al. 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: 289-295 doi:10.1097/IGC.0b013e31820aaafd
• 11 Harter P, Beutel B, Alesina PF. et al. Prognostic and predictive value of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score in surgery for recurrent ovarian cancer. Gynecol Oncol 2014; 132: 537-541 doi:10.1016/j.ygyno.2014.01.027
• 12 Muallem MZ, Gasimli K, Richter R. et al. AGO score as a predictor of surgical outcome at secondary cytoreduction in patients with ovarian cancer. Anticancer Res 2015; 35: 3423-3429
• 13 Al Rawahi T, Lopes AD, Bristow RE. et al. Surgical cytoreduction for recurrent epithelial ovarian cancer. Cochrane Database Syst Rev 2013; (02) CD008765 DOI: 10.1002/14651858.CD008765.pub3.
• 14 Coleman RL, Spirtos NM, Enserro D. et al. Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer. N Engl J Med 2019; 381: 1929-1939 doi:10.1056/NEJMoa1902626
• 15 van de Laar R, Zusterzeel PLM, Van Gorp T. et al. Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study. BMC Cancer 2014; 14: 22 doi:10.1186/1471-2407-14-22
• 16 van de Laar R, Kruitwagen RFPM, Zusterzeel PLM. et al. Correspondence: Premature Stop of the SOCceR Trial, a Multicenter Randomized Controlled Trial on Secondary Cytoreductive Surgery: Netherlands Trial Register Number: NTR3337. Int J Gynecol Cancer 2017; 27: 2 doi:10.1097/IGC.0000000000000841
• 17 Grunewald T, Tang M, Chen J. et al. Where have we gone wrong? Phase II trials (Ph2 t) do not inform the results of phase III trials (Ph3 t) in platinum resistant ovarian cancer (PROC). J Clin Oncol 2016; 34 (15_suppl): 5559 doi:10.1200/jco.2016.34.15_suppl.5559
• 18 Roncolato FT, Berton-Rigaud D, OʼConnell R. et al. Validation of the modified Glasgow Prognostic Score (mGPS) in recurrent ovarian cancer (ROC) – Analysis of patients enrolled in the GCIG Symptom Benefit Study (SBS). Gynecol Oncol 2018; 148: 36-41 doi:10.1016/j.ygyno.2017.10.019
• 19 Hanker LC, Loibl S, Burchardi N. et al. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann Oncol 2012; 23: 2605-2612 doi:10.1093/annonc/mds203
• 20 Friedlander ML, Stockler M, OʼConnell R. et al. Symptom Burden and Outcomes of Patients With Platinum Resistant/Refractory Recurrent Ovarian Cancer: A Reality Check. Int J Gynecol Cancer 2014; 24: 857-864 doi:10.1097/IGC.0000000000000147
• 21 Corrado G, Salutari V, Palluzzi E. et al. Optimizing treatment in recurrent epithelial ovarian cancer. Expert Rev Anticancer Ther 2017; 17: 1147-1158 doi:10.1080/14737140.2017.1398088
• 22 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 doi:10.1200/JCO.2006.09.6735
• 23 Markman M, Blessing J, Rubin SC. 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 doi:10.1016/j.ygyno.2005.10.036
• 24 Rose PG, Blessing JA, Mayer AR. et al. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: A Gynecologic Oncology Group study. J Clin Oncol 1998; 16: 405-410 doi:10.1200/JCO.1998.16.2.405
• 25 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 doi:10.1200/JCO.2001.19.14.3312
• 26 Coleman RL, Brady W, McMeekin DS. et al. A phase II evaluation of nab-paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: A Gynecologic Oncology Group (GOG) study. J Clin Oncol 2010; 28 (15_suppl): 5010 doi:10.1200/jco.2010.28.15_suppl.5010
• 27 Safra T, Borgato L, Nicoletto MO. et al. BRCA mutation status and determinant of outcome in women with recurrent epithelial ovarian cancer treated with pegylated liposomal doxorubicin. Mol Cancer Ther 2011; 10: 2000-2007 doi:10.1158/1535-7163.MCT-11-0272
• 28 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; DOI: 10.1016/j.annonc.2020.08.2260.
• 29 Pujade-Lauraine E. et al. Errata: Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial (J Clin Oncol 32: 1302–1308, 2014). J Clin Oncol 2014; 32: 4025 doi:10.1200/JCO.2014.60.0064
• 30 Eisenhauer EA, Vermorken JB, Van Glabbeke M. Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: A multivariate analysis of 704 patients. Ann Oncol 1997; 8: 963-968 doi:10.1023/A:1008240421028
• 31 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 doi:10.1200/JCO.2017.73.4293
• 32 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; DOI: 10.1016/j.annonc.2020.08.2260.
• 33 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 doi:10.1093/annonc/mdq352
• 34 Pfisterer J, Dean AP, Baumann K. et al. Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab (CD-BEV) Carboplatin/Gemcitabine/Bevacizumab (CG-BEV) in patients with recurrent ovarian cancer. Ann Oncol 2018; 29 (suppl_8): viii332-viii258
• 35 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 doi:10.1056/NEJMoa1104390
• 36 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 doi:10.1016/j.ygyno.2015.08.004
• 37 Coleman RL, Enserro D, Spirtos N. et al. A phase III randomized controlled trial of secondary surgical cytoreduction (SSC) followed by platinum-based combination chemotherapy (PBC), with or without bevacizumab (B) in platinum-sensitive, recurrent ovarian cancer (PSOC): A NRG Oncology/Gynecologic Oncology Group (GOG) study. J Clin Oncol 2018; 36 (15_suppl): 5501 doi:10.1200/JCO.2018.36.15_suppl.5501
• 38 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 (15_suppl): 5506 doi:10.1200/jco.2018.36.15_suppl.5506
• 39 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 doi:10.1371/journal.pone.0186043
• 40 Bell D, Berchuck A, Birrer M. et al. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474: 609-615 doi:10.1038/nature10166
• 41 Incorvaia L, Passiglia F, Rizzo S. et al. “Back to a false normality”: New intriguing mechanisms of resistance to PARP inhibitors. Oncotarget 2017; DOI: 10.18632/oncotarget.14409.
• 42 Kristeleit RS, Miller RE, Kohn EC. Gynecologic Cancers: Emerging Novel Strategies for Targeting DNA Repair Deficiency. Am Soc Clin Oncol Educ B 2016; DOI: 10.1200/edbk_159086.
• 43 Richters LK, Schouten PC, Kommoss S. et al. BRCA-like classification in ovarian cancer: Results from the AGO-TR1-trial. J Clin Oncol 2017; 35 (15_suppl): 5546 doi:10.1200/JCO.2017.35.15_suppl.5546
• 44 Xu K, Yang S, Zhao Y. Prognostic significance of BRCA mutations in ovarian cancer: An updated systematic review with meta-analysis. Oncotarget 2017; 8: 285-302 doi:10.18632/oncotarget.12306
• 45 Konstantinopoulos PA, Spentzos D, Karlan BY. et al. Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer. J Clin Oncol 2010; 28: 3555-3561 doi:10.1200/JCO.2009.27.5719 Erratum in: J Clin Oncol 2010; 28: 4868 Erratum in: J Clin Oncol 2010; 28: 4868
• 46 Ledermann JA, Pujade-Lauraine E. Olaparib as maintenance treatment for patients with platinum-sensitive relapsed ovarian cancer. Ther Adv Med Oncol 2019; 11: 1758835919849753 doi:10.1177/1758835919849753
• 47 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 doi:10.1016/S1470-2045(17)30469-2
• 48 Poveda A, Floquet A, Ledermann JA. et al. Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation. J Clin Oncol 2020; 38(15_suppl): 6002 doi:10.1200/JCO.2020.38.15_suppl.6002
• 49 Domchek SM, Aghajanian C, Shapira-Frommer R. et al. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy. Gynecol Oncol 2016; 140: 199-203 doi:10.1016/j.ygyno.2015.12.020
• 50 Penson RT, Villalobos Valencia R, Cibula D. et al. Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial. J Clin Oncol 2019; 37(15_suppl): 5506 doi:10.1200/jco.2019.37.15_suppl.5506
• 51 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 doi:10.1056/NEJMoa1611310
• 52 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 doi:10.1016/S1470-2045(19)30029-4
• 53 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 doi:10.1016/S1470-2045(16)30559-9
• 54 Kristeleit RS, Shapira-Frommer R, Oaknin A. et al. Clinical activity of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with high-grade ovarian carcinoma (HGOC) and a BRCA mutation (BRCAmut): Analysis of pooled data from Study 10 (parts 1, 2a, and 3) and ARIEL2 (parts 1 and 2). Ann Oncol 2016; 27: vi296 doi:10.1093/annonc/mdw374.03
• 55 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 doi:10.1016/S0140-6736(17)32440-6
• 56 Yokoyama Y. Recurrent epithelial ovarian cancer and hormone therapy. World J Clin Cases 2013; 1: 187 doi:10.12998/wjcc.v1.i6.187
• 57 Markman M, Iseminger KA, Hatch KD. et al. Tamoxifen in Platinum-Refractory Ovarian Cancer: A Gynecologic Oncology Group Ancillary Report. Gynecol Oncol 1996; 62: 4-6 doi:10.1006/gyno.1996.0181
• 58 Rao GG, Miller DS. Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther 2006; 6: 43-47 doi:10.1586/14737140.6.1.43
• 59 Papadimitriou CA, Markaki S, Siapkaras J. et al. Hormonal Therapy with Letrozole for Relapsed Epithelial Ovarian Cancer. Oncology 2004; 66: 112-117 doi:10.1159/000077436
• 60 de Carmen MG, Fuller AF, Matulonis U. et al. Phase II trial of anastrozole in women with asymptomatic müllerian cancer. Gynecol Oncol 2003; 91: 596-602 doi:10.1016/j.ygyno.2003.08.021
• 61 Ramirez PT, Schmeler KM, Milam MR. et al. Efficacy of letrozole in the treatment of recurrent platinum- and taxane-resistant high-grade cancer of the ovary or peritoneum. Gynecol Oncol 2008; 110: 56-59 doi:10.1016/j.ygyno.2008.03.014
• 62 Gershenson DM, Miller A, Brady W. et al. A RANDOMIZED PHASE II/III STUDY TO ASSESS THE EFFICACY OF TRAMETINIB IN PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE SEROUS OVARIAN OR PERITONEAL CANCER. Ann Oncol 2019; 30(suppl_5): v851-v934 doi:10.1093/annonc/mdz394
• 63 Ricciardi E, Baert T, Ataseven B. et al. Low-grade Serous Ovarian Carcinoma. Geburtshilfe Frauenheilkd 2018; 78: 972-976 doi:10.1055/a-0717-5411
• 64 Moore KN, Bookman M, Sehouli J. et al. LBA31 Primary results from IMagyn050/GOG 3015/ENGOT-OV39, a double-blind placebo (pbo)-controlled randomised phase III trial of bevacizumab (bev)-containing therapy ± atezolizumab (atezo) for newly diagnosed stage III/IV ovarian cancer (OC). Ann Oncol 2020; DOI: 10.1016/j.annonc.2020.08.2261.
• 65 Le DT, Durham JN, Smith KN. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017; 357: 409-413 doi:10.1126/science.aan6733
• 66 Marcus L, Lemery SJ, Keegan P. et al. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. Clin Cancer Res 2019; 25: 3753-3758 doi:10.1158/1078-0432.CCR-18-4070
• 67 Hartkopf AD, Müller V, Wöckel A. et al. Translational Highlights in Breast and Ovarian Cancer 2019 – Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy. Geburtshilfe Frauenheilkd 2019; 79: 1309-1319 doi:10.1055/a-1039-4458
• 68 Pujade-Lauraine E, Fujiwara K, Ledermann JA. et al. Avelumab alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in platinum-resistant or refractory epithelial ovarian cancer: Primary and biomarker analysis of the phase III JAVELIN Ovarian 200 trial. Gynecol Oncol 2019; 154: 21-22 doi:10.1016/j.ygyno.2019.04.053