Ovarian cancer - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main ovarian cancer page for regimens that include active anticancer treatment.
=Adjuvant therapy for early stage disease=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Young et al. 1990 	1976-1984 	Phase 3 (C)	Melphalan 	Did not meet efficacy endpoints
Trimbos et al. 2003 (ACTION) 	1990-2000 	Phase 3 (C)	Platinum-based chemotherapy	Shorter OS1
Colombo et al. 2003 (ICON1) 	1991-2000 	Phase 3 (C)	Platinum-based chemotherapy	Shorter OS1
Mannel et al. 2011 (GOG-0175)	1998-2006 	Phase 3 (C)	Paclitaxel 	Did not meet primary endpoint of RR
1Reported efficacy for ACTION and ICON1 is based on the 2003 pooled update.
No further treatment.
====Preceding treatment====
*Young et al. 1990, ACTION, ICON1: Surgery
*GOG-0175: Surgery, then adjuvant Carboplatin & Paclitaxel x 3
===References===
# Young RC, Walton LA, Ellenberg SS, Homesley HD, Wilbanks GD, Decker DG, Miller A, Park R, Major F Jr. Adjuvant therapy in stage I and stage II epithelial ovarian cancer: results of two prospective randomized trials. N Engl J Med. 1990 Apr 12;322(15):1021-7. link to original article EuroPMC
# ACTION: Trimbos JB, Vergote I, Bolis G, Vermorken JB, Mangioni C, Madronal C, Franchi M, Tateo S, Zanetta G, Scarfone G, Giurgea L, Timmers P, Coens C, Pecorelli S; EORTC-ACTION collaborators. Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial. J Natl Cancer Inst. 2003 Jan 15;95(2):113-25. link to original article EuroPMC
## Meta-analysis: Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; EORTC Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm. 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 Jan 15;95(2):105-12. link to original article EuroPMC
# ICON1: Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM, Torri V, Williams C, Lissoni A, Bonazzi C; ICON. International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst. 2003 Jan 15;95(2):125-32. link to original article EuroPMC NCT00002477
## Meta-analysis: Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; EORTC Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm. 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 Jan 15;95(2):105-12. link to original article EuroPMC
# GOG-0175: Mannel RS, Brady MF, Kohn EC, Hanjani P, Hiura M, Lee R, Degeest K, Cohn DE, Monk BJ, Michael H. A randomized phase III trial of IV carboplatin and paclitaxel x 3 courses followed by observation versus weekly maintenance low-dose paclitaxel in patients with early-stage ovarian carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2011 Jul;122(1):89-94. Epub 2011 May 6. link to original article link to PMC article EuroPMC NCT00003644
=Maintenance after first-line therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Piccart et al. 2003 (EORTC 55875) 	1988-1997 	Phase 3 (C)	Cisplatin; IP 	Did not meet primary endpoint of OS
Hall et al. 2004 	1990-1997 	Phase 3 (C)	IFN alfa-2a 	Did not meet primary endpoint of OS
De Placido et al. 2004 (MITO-1) 	1998-2002 	Phase 3 (C)	Topotecan 	Did not meet primary endpoint of PFS
Pfisterer et al. 2006 (AGO-OVAR 7) 	1999-2002 	Phase 3 (C)	Topotecan 	Did not meet primary endpoint of OS
Pecorelli et al. 2009 (After-6 protocol 1)	1999-2006 	Phase 3 (C)	Paclitaxel 	Did not meet primary endpoint of PFS
Vergote et al. 2013 (EORTC 55041) 	2005-2008 	Phase 3 (C)	Erlotinib 	Did not meet primary endpoint of PFSMedian PFS: 12.4 vs 12.7 mo(HR 0.95, 95% CI 0.81-1.11)
Copeland et al. 2022 (GOG 0212) 	2005-2014 	Phase 3 (C)	1. Paclitaxel2. Paclitaxel poliglumex	Did not meet primary endpoint of OS
No further treatment.
====Preceding treatment====
*AGO-OVAR 7: First-line TC x 6-10
*EORTC 55041: Debulking surgery (primary or interval) & First-line platinum-based chemotherapy x 6 to 9, with SD or better
*GOG 0212: First-line platinum-taxane-based chemotherapy
===References===
# EORTC 55875: Piccart MJ, Floquet A, Scarfone G, Willemse PH, Emerich J, Vergote I, Giurgea L, Coens C, Awada A, Vermorken JB. Intraperitoneal cisplatin versus no further treatment: 8-year results of EORTC 55875, a randomized phase III study in ovarian cancer patients with a pathologically complete remission after platinum-based intravenous chemotherapy. Int J Gynecol Cancer. 2003 Nov-Dec;13 Suppl 2:196-203. link to original article EuroPMC
# MITO-1: De Placido S, Scambia G, Di Vagno G, Naglieri E, Lombardi AV, Biamonte R, Marinaccio M, Cartenì G, Manzione L, Febbraro A, De Matteis A, Gasparini G, Valerio MR, Danese S, Perrone F, Lauria R, De Laurentiis M, Greggi S, Gallo C, Pignata S. Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study. J Clin Oncol. 2004 Jul 1;22(13):2635-42. link to original article EuroPMC
# Hall GD, Brown JM, Coleman RE, Stead M, Metcalf KS, Peel KR, Poole C, Crawford M, Hancock B, Selby PJ, Perren TJ. Maintenance treatment with interferon for advanced ovarian cancer: results of the Northern and Yorkshire gynaecology group randomised phase III study. Br J Cancer. 2004 Aug 16;91(4):621-6. link to original article link to PMC article EuroPMC
# AGO-OVAR 7: Pfisterer J, Weber B, Reuss A, Kimmig R, du Bois A, Wagner U, Bourgeois H, Meier W, Costa S, Blohmer JU, Lortholary A, Olbricht S, Stähle A, Jackisch C, Hardy-Bessard AC, Möbus V, Quaas J, Richter B, Schröder W, Geay JF, Lück HJ, Kuhn W, Meden H, Nitz U, Pujade-Lauraine E; AGO-OVAR; GINECO. Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO. J Natl Cancer Inst. 2006 Aug 2;98(15):1036-45. link to original article EuroPMC NCT00006454
# After-6 protocol 1: Pecorelli S, Favalli G, Gadducci A, Katsaros D, Panici PB, Carpi A, Scambia G, Ballardini M, Nanni O, Conte P; After 6 Italian Cooperative Group. Phase III trial of observation versus six courses of paclitaxel in patients with advanced epithelial ovarian cancer in complete response after six courses of paclitaxel/platinum-based chemotherapy: final results of the After-6 protocol 1. J Clin Oncol. 2009 Oct 1;27(28):4642-8. Epub 2009 Aug 24. link to original article EuroPMC
# EORTC 55041: Vergote IB, Jimeno A, Joly F, Katsaros D, Coens C, Despierre E, Marth C, Hall M, Steer CB, Colombo N, Lesoin A, Casado A, Reinthaller A, Green J, Buck M, Ray-Coquard I, Ferrero A, Favier L, Reed NS, Curé H, Pujade-Lauraine E. Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study. J Clin Oncol. 2014 Feb 1;32(4):320-6. Epub 2013 Dec 23. link to original article EuroPMC NCT00263822
# GOG 0212: Copeland LJ, Brady MF, Burger RA, Rodgers WH, Huang HQ, Cella D, O'Malley DM, Street DG, Tewari KS, Bender DP, Morris RT, Lowery WJ, Miller DS, Dewdney SB, Spirtos NM, Lele SB, Guntupalli S, Ueland FR, Glaser GE, Mannel RS, DiSaia PJ. Phase III Randomized Trial of Maintenance Taxanes Versus Surveillance in Women With Advanced Ovarian/Tubal/Peritoneal Cancer: A Gynecologic Oncology Group 0212:NRG Oncology Study. J Clin Oncol. 2022 Dec 10;40(35):4119-4128. Epub 2022 Jun 27. link to original article link to PMC article EuroPMC NCT00108745
==Placebo==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Hirte et al. 2006 	1998-05-05 to 1999-09-20	Phase 3 (C)	Tanomastat	Did not meet primary endpoint of TTP
Berek et al. 2008 (OVA-Gy-17) 	2002 to not reported 	Phase 3 (C)	Oregovomab	Did not meet primary endpoint of time to response
Sabbatini et al. 2013 (MIMOSA) 	2006-2009 	Phase 3 (C)	Abagovomab	Did not meet primary endpoint of RFS
Du Bois et al. 2014 (AGO-OVAR 16) 	2009-06 to 2010-08 	Phase 3 (C)	Pazopanib 	Shorter PFSMedian PFS: 12.3 vs 17.9 mo(HR 1.30, 95% CI 1.10-1.56)
Moore et al. 2018 (SOLO1) 	2013-2015 	Phase 3 (C)	Olaparib 	Shorter OS1
González-Martín et al. 2019 (PRIMAOV)	2016-2018 	Phase 3 (C)	Niraparib 	Shorter PFS2 (primary endpoint)Median PFS: 8.2 vs 13.8 mo(HR 1.52, 95% CI 1.27-1.79)
Monk et al. 2022 (ATHENA-MONO) 	2018-2020 	Phase 3 (C)	Rucaparib 	Shorter PFSMedian PFS: 9.2 vs 20.2 mo(HR 1.92, 95% CI 1.47-2.50)
Wu et al. 2024 (FLAMES) 	2019-11-27 to 2021-09-24	Phase 3 (C)	Senaparib 	Shorter PFS (primary endpoint)Median PFS: 13.6 vs NYR mo(HR 2.33, 95% CI 1.72-3.12)
1Reported efficacy for SOLO1 is based on the 2022 update; the OS result did not meet the authors' predefined level of statistical significance, which was based on P-value.
2Reported efficacy for PRIMAOV is for the overall population and is based on the 2023 update.
No active antineoplastic treatment after initial treatment.
====Preceding treatment====
*MIMOSA: Debulking surgery, then first-line platinum-taxane-based chemotherapy x 6 to 8, with CR
*AGO-OVAR 16: Debulking surgery (primary or interval), then first-line platinum-taxane-based chemotherapy for at least 5 cycles, with SD or better
*PRIMAOV: First-line Platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
*ATHENA-MONO & FLAMES: First-line Platinum doublet chemotherapy
===References===
# Hirte H, Vergote IB, Jeffrey JR, Grimshaw RN, Coppieters S, Schwartz B, Tu D, Sadura A, Brundage M, Seymour L; National Cancer Institute of Canada Clinical Trials Group. A phase III randomized trial of BAY 12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy: a National Cancer Institute of Canada Clinical Trials Group study. Gynecol Oncol. 2006 Aug;102(2):300-8. Epub 2006 Jan 25. link to original article EuroPMC
# OVA-Gy-17: Berek J, Taylor P, McGuire W, Smith LM, Schultes B, Nicodemus CF. Oregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer. J Clin Oncol. 2009 Jan 20;27(3):418-25. Epub 2008 Dec 15. link to original article EuroPMC NCT00050375
# MIMOSA: 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 Apr 20;31(12):1554-61. Epub 2013 Mar 11. link to original article link to PMC article EuroPMC NCT00418574
# AGO-OVAR 16: 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 Oct 20;32(30):3374-82. Epub 2014 Sep 15. link to original article EuroPMC NCT00866697
## Subgroup analysis: Kim JW, Mahner S, Wu LY, Shoji T, Kim BG, Zhu JQ, Takano T, Park SY, Kong BH, Wu Q, Wang KL, Ngan HY, Liu JH, Wei LH, Mitrica I, Zhang P, Crescenzo R, Wang Q, Cox CJ, Harter P, du Bois A. Pazopanib maintenance therapy in East Asian women with advanced epithelial ovarian cancer: results from AGO-OVAR16 and an East Asian Study. Int J Gynecol Cancer. 2018 Jan;28(1):2-10. link to original article EuroPMC
## Update: Vergote I, du Bois A, Floquet A, Rau J, Kim JW, Del Campo JM, Friedlander M, Pignata S, Fujiwara K, Colombo N, Mirza MR, Monk BJ, Tsibulak I, Calvert PM, Herzog TJ, Hanker LC, Meunier J, Lee JY, Bologna A, Carrasco-Alfonso MJ, Harter P. Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. Gynecol Oncol. 2019 Nov;155(2):186-191. Epub 2019 Sep 10. link to original article EuroPMC
# SOLO1: Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018 Dec 27;379(26):2495-2505. Epub 2018 Oct 21. link to original article EuroPMC NCT01844986
##Subgroup analysis: DiSilvestro P, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian CA, Bradley WH, Mathews CA, Liu J, Lowe ES, Bloomfield R, Moore KN. Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial. J Clin Oncol. 2020 Oct 20;38(30):3528-3537. Epub 2020 Aug 4. link to original article link to PMC article EuroPMC
## HRQoL analysis: Friedlander M, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Lisyanskaya A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley WH, Liu J, Mathews C, Selle F, Lortholary A, Lowe ES, Hettle R, Flood E, Parkhomenko E, DiSilvestro P. Patient-centred outcomes and effect of disease progression on health status in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation receiving maintenance olaparib or placebo (SOLO1): a randomised, phase 3 trial. Lancet Oncol. 2021 May;22(5):632-642. Epub 2021 Apr 13. link to original article EuroPMC
## Update: Banerjee S, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley WH, Holmes E, Lowe ES, DiSilvestro P. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1721-1731. Epub 2021 Oct 26. Erratum in: Lancet Oncol. 2021 Dec;22(12):e539. link to original article EuroPMC
## Update: DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, McNamara J, Lowe ES, Ah-See ML, Moore KN; SOLO1 Investigators. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol. 2023 Jan 20;41(3):609-617. Epub 2022 Sep 9. link to original article link to PMC article EuroPMC
# PRIMAOV: González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. Epub 2019 Sep 28. link to original article EuroPMC NCT02655016
##Q-TWiST analysis: Barretina-Ginesta MP, Monk BJ, Han S, Pothuri B, Auranen A, Chase DM, Lorusso D, Anderson C, Abadie-Lacourtoisie S, Cloven N, Braicu EI, Amit A, Redondo A, Shah R, Kebede N, Hawkes C, Gupta D, Woodward T, O'Malley DM, González-Martín A. Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial. Ther Adv Med Oncol. 2022 Sep 22;14:17588359221126149. link to original article link to PMC article EuroPMC
##Update: González-Martín A, Pothuri B, Vergote I, Graybill W, Lorusso D, McCormick CC, Freyer G, Backes F, Heitz F, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Malinowska IA, Shtessel L, Compton N, Mirza MR, Monk BJ. Progression-free survival and safety at 3.5years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. Eur J Cancer. 2023 Aug;189:112908. Epub 2023 May 3. link to original article EuroPMC
##HRQoL analysis: Pothuri B, Han S, Chase DM, Heitz F, Burger RA, Gaba L, Van Le L, Guerra E, Bender D, Korach J, Cloven N, Churruca C, Follana P, DiSilvestro P, Baurain JF, Jardon K, Pisano C, Peen U, Mäenpää J, Gupta D, Bacqué E, Li Y, Compton N, Antonova J, Monk BJ, González-Martín A. Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial. Gynecol Oncol. 2024 May;184:168-177. Epub 2024 Feb 6. link to original article EuroPMC
##Update: Monk BJ, Barretina-Ginesta MP, Pothuri B, Vergote I, Graybill W, Mirza MR, McCormick CC, Lorusso D, Moore RG, Freyer G, O'Cearbhaill RE, Heitz F, O'Malley DM, Redondo A, Shahin MS, Vulsteke C, Bradley WH, Haslund CA, Chase DM, Pisano C, Holman LL, Pérez MJR, DiSilvestro P, Gaba L, Herzog TJ, Bruchim I, Compton N, Shtessel L, Malinowska IA, González-Martín A. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Ann Oncol. 2024 Nov;35(11):981-992. Epub 2024 Sep 14. link to original article EuroPMC
# ATHENA-MONO: Monk BJ, Parkinson C, Lim MC, O'Malley DM, Oaknin A, Wilson MK, Coleman RL, Lorusso D, Bessette P, Ghamande S, Christopoulou A, Provencher D, Prendergast E, Demirkiran F, Mikheeva O, Yeku O, Chudecka-Glaz A, Schenker M, Littell RD, Safra T, Chou HH, Morgan MA, Drochýtek V, Barlin JN, Van Gorp T, Ueland F, Lindahl G, Anderson C, Collins DC, Moore K, Marme F, Westin SN, McNeish IA, Shih D, Lin KK, Goble S, Hume S, Fujiwara K, Kristeleit RS. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022 Dec 1;40(34):3952-3964. Epub 2022 Jun 6. link to original article link to PMC article EuroPMC NCT03522246
#FLAMES: Wu X, Liu J, Wang J, Wang L, Lin Z, Wang X, Zhu J, Kong B, Fei J, Tang Y, Xia B, Liang Z, Wang K, Huang Y, Zheng H, Lin A, Jiang K, Wang W, Wang X, Lou G, Pan H, Yao S, Li G, Hao M, Cai Y, Chen X, Yang Z, Chen Y, Wen H, Qu P, Xu C, Hsieh CY; FLAMES Investigators. Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial. Nat Med. 2024 Jun;30(6):1612-1621. Epub 2024 May 15. link to original article EuroPMC NCT04169997
#MAMOC: NCT04227522
#MATAO: NCT04111978
=Maintenance after second-line therapy for platinum-sensitive disease=
==Placebo==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Ledermann et al. 2016 (ICON6) 	2007-2011 	Phase 3 (C) 	Cediranib 	Shorter PFS (primary endpoint)Median PFS: 8.7 vs 11 mo(HR 1.79, 95% CI 1.39-2.27)
Ledermann et al. 2012 (Study 19) 	2008-2010 	Randomized Phase 2 (C)	Olaparib 	Might have shorter OS1
Mirza et al. 2016 (NOVA) 	2013 to not reported 	Phase 3 (C) 	Niraparib 	Shorter PFSMedian PFS: 3.9 vs 9.3 mo(HR 2.22, 95% CI 1.64-2.94)
Pujade-Lauraine et al. 2017 (SOLO2)	2013-09-03 to 2014-11-21	Phase 3 (C) 	Olaparib 	Seems to have shorter OS2
Coleman et al. 2017 (ARIEL3) 	2014-2016 	Phase 3 (C) 	Rucaparib 	Shorter PFSMedian PFS: 5.4 vs 16.6 mo(HR 4.35, 95% CI 2.94-6.25)
Pujade-Lauraine et al. 2023 (OReO) 	2017-06-28 to 2021-02-10	Phase 3b (C) 	Olaparib 	Shorter PFSMedian PFS: 2.8 vs 5.3 mo(HR 2.33, 95% CI 1.41-3.85)
Li et al. 2022 (FZOCUS-2) 	2019-04-30 to 2020-01-10	Phase 3 (C) 	Fuzuloparib	Shorter PFS (primary endpoint)Median PFS: 5.5 vs 12.9 mo(HR 4.00, 95% CI 2.78-5.88)
1Reported efficacy for Study 19 is based on the 2018 update; although p=0.02, the authors state that "the predefined threshold for statistical significance was not met."
2Reported efficacy for SOLO2 is based on the 2021 update.
No further active antineoplastic treatment.
====Preceding treatment====
*Second-line platinum-based chemotherapy
===References===
# Study 19: Ledermann J1, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. Epub 2012 Mar 27. link to original article EuroPMC NCT00753545
## Update: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. Epub 2016 Sep 8. link to orignal article EuroPMC
## HRQoL analysis: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Bennett B, Parry D, Spencer S, Mann H, Matulonis U. Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer. Br J Cancer. 2016 Nov 22;115(11):1313-1320. Epub 2016 Nov 8. link to original article link to PMC article EuroPMC
## Update: Friedlander M, Matulonis U, Gourley C, du Bois A, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Shirinkin V, Selle F, Fielding A, Lowe ES, McMurtry EL, Spencer S, Rowe P, Mann H, Parry D, Ledermann J. Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. Br J Cancer. 2018 Oct;119(9):1075-1085. Epub 2018 Oct 24. link to original article link to PMC article EuroPMC
# ICON6: Ledermann JA, Embleton AC, Raja F, Perren TJ, Jayson GC, Rustin GJS, Kaye SB, Hirte H, Eisenhauer E, Vaughan M, Friedlander M, González-Martín A, Stark D, Clark E, Farrelly L, Swart AM, Cook A, Kaplan RS, Parmar MKB; ICON. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016 Mar 12;387(10023):1066-1074. Erratum in: Lancet. 2016 Apr 23;387(10029):1722. link to original article EuroPMC NCT00532194
##HRQoL analysis: Stark DP, Cook A, Brown JM, Brundage MD, Embleton AC, Kaplan RS, Raja FA, Swart AMW, Velikova G, Qian W, Ledermann JA. Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial. Cancer. 2017 Jul 15;123(14):2752-2761. Epub 2017 Mar 24. link to original article link to PMC article EuroPMC
## Update: Ledermann JA, Embleton-Thirsk AC, Perren TJ, Jayson GC, Rustin GJS, Kaye SB, Hirte H, Oza A, Vaughan M, Friedlander M, González-Martín A, Deane E, Popoola B, Farrelly L, Swart AM, Kaplan RS, Parmar MKB; ICON6 collaborators. Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial. ESMO Open. 2021 Apr;6(2):100043. Epub 2021 Feb 18. link to original article link to PMC article EuroPMC
# NOVA: 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, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016 Dec 1;375(22):2154-64. Epub 2016 Oct 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01847274
## PRO analysis: Oza AM, Matulonis UA, Malander S, Hudgens S, Sehouli J, Del Campo JM, Berton-Rigaud D, Banerjee S, Scambia G, Berek JS, Lund B, Tinker AV, Hilpert F, Vázquez IP, D'Hondt V, Benigno B, Provencher D, Buscema J, Agarwal S, Mirza MR. Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2018 Aug;19(8):1117-1125. Epub 2018 Jul 17. link to original article EuroPMC
## Subgroup analysis: Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, Waters J, Berek JS, Woie K, Oza AM, Canzler U, Gil-Martin M, Lesoin A, Monk BJ, Lund B, Gilbert L, Wenham RM, Benigno B, Arora S, Hazard SJ, Mirza MR. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Nov 10;37(32):2968-2973. Epub 2019 Jun 7. link to original article link to PMC article EuroPMC
## Update: Mirza MR, Benigno B, Dørum A, Mahner S, Bessette P, Barceló IB, Berton-Rigaud D, Ledermann JA, Rimel BJ, Herrstedt J, Lau S, du Bois A, Casado Herráez A, Kalbacher E, Buscema J, Lorusso D, Vergote I, Levy T, Wang P, de Jong FA, Gupta D, Matulonis UA. Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol Oncol. 2020 Nov;159(2):442-448. Epub 2020 Sep 25. link to original article EuroPMC
# SOLO2: Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. 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 Sep;18(9):1274-1284. Epub 2017 Jul 25. link to original article EuroPMC NCT01874353
##HRQoL analysis: Friedlander M, Gebski V, Gibbs E, Davies L, Bloomfield R, Hilpert F, Wenzel LB, Eek D, Rodrigues M, Clamp A, Penson RT, Provencher D, Korach J, Huzarski T, Vidal L, Salutari V, Scott C, Nicoletto MO, Tamura K, Espinoza D, Joly F, Pujade-Lauraine E. Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial. Lancet Oncol. 2018 Aug;19(8):1126-1134. Epub 2018 Jul 17. link to original article link to PMC article EuroPMC
## Update: Poveda A, Floquet A, Ledermann JA, Asher R, Penson RT, Oza AM, Korach J, Huzarski T, Pignata S, Friedlander M, Baldoni A, Park-Simon TW, Tamura K, Sonke GS, Lisyanskaya A, Kim JH, Filho EA, Milenkova T, Lowe ES, Rowe P, Vergote I, Pujade-Lauraine E; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):620-631. Epub 2021 Mar 18. link to original article EuroPMC
# ARIEL3: Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12. link to original article link to PMC article EuroPMC NCT01968213
## Update: Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. link to original article link to PMC article EuroPMC
## Update: Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cella D, Meunier J, Goble S, Cameron T, Maloney L, Mörk AC, Bedel J, Ledermann JA, Coleman RL. Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients With Recurrent Ovarian Carcinoma. J Clin Oncol. 2020 Oct 20;38(30):3494-3505. Epub 2020 Aug 24. link to original article link to PMC article EuroPMC
##PRO analysis: Peipert JD, Goble S, Isaacson J, Tang X, Wallace K, Coleman RL, Ledermann JA, Cella D. Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial. Gynecol Oncol. 2023 Aug;175:1-7. Epub 2023 May 30. link to original article EuroPMC
# NORA: Wu XH, Zhu JQ, Yin RT, Yang JX, Liu JH, Wang J, Wu LY, Liu ZL, Gao YN, Wang DB, Lou G, Yang HY, Zhou Q, Kong BH, Huang Y, Chen LP, Li GL, An RF, Wang K, Zhang Y, Yan XJ, Lu X, Lu WG, Hao M, Wang L, Cui H, Chen QH, Abulizi G, Huang XH, Tian XF, Wen H, Zhang C, Hou JM, Mirza MR. Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2021 Apr;32(4):512-521. Epub 2021 Jan 14. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03705156
##Update: Wu X, Zhu J, Yin R, Yang J, Liu J, Wang J, Wu L, Liu Z, Gao Y, Wang D, Lou G, Yang H, Zhou Q, Kong B, Huang Y, Chen L, Li G, An R, Wang K, Zhang Y, Yan X, Lu X, Lu W, Hao M, Wang L, Cui H, Chen Q, Abulizi G, Huang X, Tian X, Wen H, Huang Z, Dong J, Zhang C, Hou J, Mirza MR. Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial. EClinicalMedicine. 2024 May 7;72:102629. link to original article link to PMC article EuroPMC
#FZOCUS-2: Li N, Zhang Y, Wang J, Zhu J, Wang L, Wu X, Yao D, Wu Q, Liu J, Tang J, Yin R, Lou G, An R, Zhang G, Xia X, Li Q, Zhu Y, Zheng H, Yang X, Hu Y, Zhang X, Hao M, Huang Y, Lin Z, Wang D, Guo X, Yao S, Wan X, Zhou H, Yao L, Yang X, Cui H, Meng Y, Zhang S, Qu J, Zhang B, Zou J, Wu L. Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial. J Clin Oncol. 2022 Aug 1;40(22):2436-2446. Epub 2022 Apr 11. link to original article EuroPMC NCT03863860
#OReO: Pujade-Lauraine E, Selle F, Scambia G, Asselain B, Marmé F, Lindemann K, Colombo N, Mądry R, Glasspool R, Vergote I, Korach J, Lheureux S, Dubot C, Oaknin A, Zamagni C, Heitz F, Gladieff L, Rubio-Pérez MJ, Scollo P, Blakeley C, Shaw B, Ray-Coquard I, Redondo A; OReO/ENGOT-ov38 investigators. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial. Ann Oncol. 2023 Dec;34(12):1152-1164. Epub 2023 Oct 4. link to original article EuroPMC NCT03106987
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