Ovarian cancer

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 Alaina J. Brown, MD, MPH
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Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
This page contains regimens which were not tested in biomarker-specific or histology-specific populations.
The following links will take you to biomarker-specific subpages:

The following links will take you to histology-specific subpages:

55 regimens on this page
103 variants on this page


Guidelines

ASCO

ESMO

Older

ESMO/ESGO

NCCN

Older

SGO/ASCO

Adjuvant therapy for early stage disease

Carboplatin monotherapy

Regimen variant #1, AUC 5

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Colombo et al. 2003 (ICON1) 1991-2000 Phase 3 (E-esc) Observation Superior OS1
OS60: 82% vs 74%
(HR 0.67, 95% CI 0.50-0.90)

1Reported efficacy is based on the 2003 pooled update.
Note: this is one of the recommended regimens for the experimental arm; other regimens were also used (see original paper).

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #2, 350 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Trimbos et al. 2003 (ACTION) 1990-2000 Phase 3 (E-esc) Observation Superior OS1
OS60: 82% vs 74%
(HR 0.67, 95% CI 0.50-0.90)

1Reported efficacy is based on the 2003 pooled update.
Note: this is one of the recommended regimens for the experimental arm; other regimens were also used (see original paper). Cycle length was not specified in the paper; 21-day cycle is typical for this drug.

Preceding treatment

Chemotherapy

21-day cycle for 4 to 6 cycles (see note)

References

  1. 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 PubMed
    1. Pooled update: 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 PubMed
  2. 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 PubMed NCT00002477
    1. Pooled update: 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 PubMed

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen variant #1, 6/175

Study Dates of enrollment Evidence
Mannel et al. 2011 (GOG-0175) 1998-2006 Non-randomized part of phase 3 RCT

Preceding treatment

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment


Regimen variant #2, 7.5/175

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bell et al. 2006 (GOG 157) 1995-1998 Phase 3 (C) CP x 6 Did not meet primary endpoint of RR

Preceding treatment

Chemotherapy

21-day cycle for 3 cycles

References

  1. GOG 157: Bell J, Brady MF, Young RC, Lage J, Walker JL, Look KY, Rose GS, Spirtos NM; Gynecologic Oncology Group. 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 Sep;102(3):432-9. Epub 2006 Jul 24. link to original article contains dosing details in abstract PubMed
  2. 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 × 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 contains dosing details in manuscript PubMed NCT00003644

Neoadjuvant chemotherapy for advanced stage disease

Carboplatin & Paclitaxel (CP)

Regimen variant #1, AUC 5/175 x 3

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Kehoe et al. 2015 (CHORUS) 2004-2010 Phase 3 (E-switch-ic) Adjuvant CP Non-inferior OS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment


Regimen variant #2, AUC 5/175 x 6

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Fagotti et al. 2016 (SCORPION) 2011-2014 Phase 3 (E-switch-ic) Adjuvant CP Did not meet primary endpoint of PFS Superior QoL

Chemotherapy

21-day cycle for 6 cycles

Subsequent treatment


Regimen variant #3, AUC 6/175 x 3

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vergote et al. 2010 (EORTC 55971) 1998-2006 Phase 3 (E-switch-ic) Adjuvant CP Non-inferior OS
Kehoe et al. 2015 (CHORUS) 2004-2010 Phase 3 (E-switch-ic) Adjuvant CP Non-inferior OS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. EORTC 55971: Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; EORTC-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. link to original article contains dosing details in supplement PubMed NCT00003636
  2. CHORUS: Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, Luesley D, Perren T, Bannoo S, Mascarenhas M, Dobbs S, Essapen S, Twigg J, Herod J, McCluggage G, Parmar M, Swart AM. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015 Jul 18;386(9990):249-57. Epub 2015 May 19. link to original article contains dosing details in abstract PubMed ISRCTN74802813
  3. SCORPION: Fagotti A, Ferrandina G, Vizzielli G, Fanfani F, Gallotta V, Chiantera V, Costantini B, Margariti PA, Gueli Alletti S, Cosentino F, Tortorella L, Scambia G. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): final analysis of peri-operative outcome. Eur J Cancer. 2016 May;59:22-33. Epub 2016 Mar 19. link to original article contains dosing details in manuscript PubMed NCT01461850

First-line chemotherapy for advanced stage disease

Note: in a majority of these regimens, chemotherapy was preceded by primary debulking surgery.

Carboplatin monotherapy

Regimen variant #1, AUC 5

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Parmar et al. 1998 (ICON2) 1991-1996 Phase 3 (E-de-esc) CAP Did not meet primary endpoint of OS Less toxic
Parmar et al. 2002 (ICON3) 1995-1998 Phase 3 (C) 1. CAP
2. Carboplatin & Paclitaxel 		Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #2, AUC 6, q3wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Parmar et al. 2002 (ICON3) 1995-1998 Phase 3 (C) 1. CAP
2. Carboplatin & Paclitaxel 		Did not meet primary endpoint of OS
Banerjee et al. 2012 (SCOTROC 4) 2004-2009 Phase 3 (C) Carboplatin; dose-escalated Did not meet primary endpoint of PFS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #3, AUC 6, q4wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gore et al. 1998 1987-1995 Phase 3 (C) Carboplatin; AUC 12 x 4 Did not meet primary endpoint of OS24

Chemotherapy

28-day cycle for 6 cycles


Regimen variant #4, AUC 9

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Markman et al. 2001 (GOG 114) 1992-1995 Phase 3 (E-esc) See link See link

Preceding treatment

Chemotherapy

28-day cycle for 2 cycles

Subsequent treatment


Regimen variant #5, 400 mg/m2, q4wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Taylor et al. 1994b 1981-1984 Phase 3 (C) Cisplatin Did not meet primary endpoint of ORR
Mangioni et al. 1989 1985-1987 Phase 3 (C) Cisplatin Did not meet endpoint

Note: this variant is of historic interest.

Chemotherapy

28-day cycle for 10 cycles

References

  1. Mangioni C, Bolis G, Pecorelli S, Bragman K, Epis A, Favalli G, Gambino A, Landoni F, Presti M, Torri W, Vassena L, Zanaboni F, Marsoni S. Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin. J Natl Cancer Inst. 1989 Oct 4;81(19):1464-71. link to original article contains dosing details in abstract PubMed
  2. Taylor AE, Wiltshaw E, Gore ME, Fryatt I, Fisher C. Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer. J Clin Oncol. 1994 Oct;12(10):2066-70. link to original article contains dosing details in abstract PubMed
  3. Gore M, Mainwaring P, A'Hern R, MacFarlane V, Slevin M, Harper P, Osborne R, Mansi J, Blake P, Wiltshaw E, Shepherd J; London Gynaecological Oncology Group. Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. J Clin Oncol. 1998 Jul;16(7):2426-34. link to original article contains dosing details in abstract PubMed
  4. ICON2: Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C; ICON. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer: International Collaborative Ovarian Neoplasm Study. Lancet. 1998 Nov 14;352(9140):1571-6. link to original article contains dosing details in manuscript PubMed
  5. GOG 114: Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. 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 Feb 15;19(4):1001-7. link to original article contains dosing details in abstract PubMed
  6. ICON3: Parmar MKB, Adams M, Balestrino M, Bertelsen K, Bonazzi C, Calvert H, Colombo N, Delaloye JF, Durando A, Guthrie D, Hagen B, Harper P, Mangioni C, Perren T, Poole C, Qian W, Rustin G, Sandercock J, Tumolo S, Torri V, Vecchione F; International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet. 2002 Aug 17;360(9332):505-15. Erratum in: Lancet. 2003 Feb 22;361(9358):706. link to original article PubMed
  7. SCOTROC 4: Banerjee S, Rustin G, Paul J, Williams C, Pledge S, Gabra H, Skailes G, Lamont A, Hindley A, Goss G, Gilby E, Hogg M, Harper P, Kipps E, Lewsley LA, Hall M, Vasey P, Kaye SB; GCIG. A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG. Ann Oncol. 2013 Mar;24(3):679-87. Epub 2012 Oct 5. link to original article link to PMC article contains dosing details in abstract PubMed NCT00098878

Carboplatin & Docetaxel

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vasey et al. 2004 (SCOTROC-1) 1998-2000 Phase 3 (E-switch-ic) Carboplatin & Paclitaxel Did not meet primary endpoint of PFS

Preceding treatment

Chemotherapy

Supportive therapy

21-day cycle for 6 cycles

References

  1. SCOTROC-1: Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. link to original article contains dosing details in manuscript PubMed NCT00003998

Carboplatin & Pegylated liposomal doxorubicin

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pignata et al. 2006 (MITO-2) 2003-2007 Phase 3 (E-switch-ic) Carboplatin & Paclitaxel Did not meet primary endpoint of PFS

Eligibility criteria for MITO-2 included: "a cytologic or histologic diagnosis of epithelial ovarian cancer (stage IC to IV according to International Federation of Gynecology and Obstetrics staging system).

Preceding treatment

Chemotherapy

Supportive therapy

  • "No prophylactic use of G-CSF was recommended. Therapeutic and prophylactic use of G-CSF was allowed for febrile or afebrile grade 4 neutropenia."

21-day cycle for 3 to 6 cycles All patients received 3 cycles of therapy. Patients with stable or responsive disease received an additional 3 cycles.

References

  1. MITO-2: Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00326456
    1. Update: Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, Gebbia V, Musso P, Frigerio L, Del Medico P, Lombardi AV, Febbraro A, Scollo P, Ferro A, Tamberi S, Brandes A, Ravaioli A, Valerio MR, Aitini E, Natale D, Scaltriti L, Greggi S, Pisano C, Lorusso D, Salutari V, Legge F, Di Maio M, Morabito A, Gallo C, Perrone F. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011 Sep 20;29(27):3628-35. Epub 2011 Aug 15. link to original article contains dosing details in manuscript PubMed

Carboplatin & Gemcitabine (GCb)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gordon et al. 2011 2002-2006 Phase 3 (E-switch-ic) Carboplatin & Paclitaxel Did not meet primary endpoint of PFS

Chemotherapy

21-day cycle for up to 6 cycles

Subsequent treatment

  • Patients with CR could optionally receive paclitaxel consolidation

References

  1. Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. link to original article contains dosing details in manuscript PubMed

Carboplatin & Paclitaxel (CP)

TC: Taxol (Paclitaxel) & Carboplatin
PC: Paclitaxel & Carboplatin

Regimen variant #1, q1wk AUC 2/60

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pignata et al. 2014 (MITO-7) 2008-2012 Phase 3 (E-switch-ic) TC; q3wk AUC 6/175 Did not meet primary endpoint of PFS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #2, q3wk AUC 5, q1wk 80

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Monk et al. 2021 (JAVELIN Ovarian 100) 2016-2018 Phase 3 (C) 1. CP & Avelumab
2. CP, then Avelumab 		Did not meet primary endpoint of PFS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #3, q3wk AUC 5/175

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Neijt et al. 2000 1994-1997 Phase 3 (E-switch-ic) Cisplatin & Paclitaxel Did not meet primary endpoint of PFS
du Bois et al. 2006 (AGO-OVAR 5) 1997-2000 Phase 3 (C) TEC Did not meet primary endpoint of OS
Vasey et al. 2004 (SCOTROC-1) 1998-2000 Phase 3 (C) Carboplatin & Docetaxel Did not meet primary endpoint of PFS
Möbus et al. 2007 (HIDOC-EIS) 1998-2004 Phase 3 (C) High-dose chemotherapy with auto HSCT Did not meet primary endpoint of PFS
Lindemann et al. 2012 (EORTC 55981) 1999-2001 Phase 3 (C) TEC Did not meet primary endpoint of PFS
Hoskins et al. 2010 (EORTC 55012) 2001-2005 Phase 3 (C) Cisplatin & Topotecan, then TC Did not meet primary endpoint of PFS Less toxic
du Bois et al. 2010 (AGO-OVAR 9) 2002-2004 Phase 3 (C) TCG Did not meet primary endpoint of OS
Pignata et al. 2006 (MITO-2) 2003-2007 Phase 3 (C) Carboplatin & PLD Did not meet primary endpoint of PFS
du Bois et al. 2015 (AGO-OVAR 12) 2009-2011 Phase 3 (C) TC & Nintedanib Seems to have inferior PFS
Fagotti et al. 2016 (SCORPION) 2011-2014 Phase 3 (C) TC; neoadjuvant Did not meet primary endpoint of PFS Inferior QoL
Clamp et al. 2019 (ICON8) 2011-2014 Phase 3 (C) 1. TC; q1wk AUC 2/80
2. TC; q3wk AUC 6, q1wk 80 ("dose-dense") 		Did not meet primary endpoints of PFS/OS
Vergote et al. 2019 (TRINOVA-3) 2012-2014 Phase 3 (C) TC & Trebananib Did not meet primary endpoint of PFS
Monk et al. 2021 (JAVELIN Ovarian 100) 2016-2018 Phase 3 (C) 1. CP & Avelumab
2. CP, then Avelumab 		Did not meet primary endpoint of PFS

Note: In MITO-2, all patients received 3 cycles of therapy. Patients with stable or responsive disease received an additional 3 cycles.

Preceding treatment

Chemotherapy

Supportive therapy

21-day cycle for 6 or more cycles (see note)


Regimen variant #4, q3wk AUC 6, q1wk 80

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Katsumata et al. 2009 (JGOG 3016) 2003-2005 Phase 3 (E-switch-ic) TC; q3wk AUC 6/180 Seems to have superior OS
OS36: 72.1% vs 65.1%
(HR 0.75, 95% CI 0.57-0.98)
Coleman et al. 2019 (VELIA) 2015-2017 Phase 3 (C) 1. CP & Veliparib x 6 Not reported
2. CP & Veliparib x 6, then Veliparib maint. Inferior PFS
Monk et al. 2021 (JAVELIN Ovarian 100) 2016-2018 Phase 3 (C) 1. CP & Avelumab
2. CP, then Avelumab 		Did not meet primary endpoint of PFS

Chemotherapy

Supportive therapy

  • "Standard premedication"

21-day cycle for 6 to 9 cycles, depending on response and protocol


Regimen variant #5, q3wk AUC 6/175

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Lhommé et al. 2008 1997-1999 Phase 3 (C) Paclitaxel & Valspodar Did not meet primary endpoint of TTP
Vergote et al. 2010 (EORTC 55971) 1998-2006 Phase 3 (C) TC x 3, then interval debulking, then TC x 3 Non-inferior OS
Gordon et al. 2011 2002-2006 Phase 3 (C) Carboplatin & Gemcitabine Did not meet primary endpoint of PFS
Bookman et al. 2009 (ICON5) 2001-2004 Phase 3 (C) 1. TCG
2. TC & PLD
3. TC & Topotecan 		Did not meet primary endpoint of OS
Alberts et al. 2008 (GRACES) 2002-2004 Phase 3 (C) CP & IFN gamma-1b Did not meet primary endpoint of OS
Burger et al. 2011 (GOG-0218) 2005-2009 Phase 3 (C) 1. TC & Bevacizumab x 6 Might have inferior PFS
2. TC & Bevacizumab x 22 Inferior PFS
Perren et al. 2011 (ICON7) 2006-2009 Phase 3 (C) Carboplatin, Paclitaxel, Bevacizumab Did not meet primary endpoints of PFS/OS1
Sugiyama et al. 2016 (JGOG3017/GCIG) 2006-2011 Phase 3 (C) Cisplatin & Irinotecan Did not meet primary endpoint of PFS
Pignata et al. 2014 (MITO-7) 2008-2012 Phase 3 (C) TC; q1wk AUC 2/60 Did not meet primary endpoint of PFS
du Bois et al. 2015 (AGO-OVAR 12) 2009-2011 Phase 3 (C) TC & Nintedanib Seems to have inferior PFS
Chan et al. 2016 (GOG-0262) 2010-2012 Phase 3 (C) TC; dose-dense Did not meet primary endpoint of PFS
Clamp et al. 2019 (ICON8) 2011-2014 Phase 3 (C) 1. TC; q1wk AUC 2/80
2. TC; q3wk AUC 6, q1wk 80 ("dose-dense") 		Did not meet primary endpoints of PFS/OS
Vergote et al. 2019 (TRINOVA-3) 2012-2014 Phase 3 (C) TC & Trebananib Did not meet primary endpoint of PFS
Coleman et al. 2019 (VELIA) 2015-2017 Phase 3 (C) 1. TC & Veliparib x 6 Not reported
2. TC & Veliparib x 6, then Veliparib maint. Inferior PFS
Monk et al. 2021 (JAVELIN Ovarian 100) 2016-2018 Phase 3 (C) 1. CP & Avelumab
2. CP, then Avelumab 		Did not meet primary endpoint of PFS

1Reported efficacy for ICON7 is based on the 2015 update.

Chemotherapy

21-day cycle for up to 6 to 8 cycles

Subsequent treatment

  • Gordon et al. 2011: Patients with CR could optionally proceed to receive paclitaxel consolidation


Regimen variant #6, q3wk AUC 6/180

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Katsumata et al. 2009 (JGOG 3016) 2003-2005 Phase 3 (C) TC; dose-dense Seems to have inferior OS

Chemotherapy

Supportive therapy

  • "Standard premedication"

21-day cycle for 6 to 9 cycles, depending on response


Regimen variant #7, AUC 6/185

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
du Bois et al. 2003 (AGO-OVAR 3) 1995-1997 Phase 3 (C) Cisplatin & Paclitaxel Non-inferior PFS Superior QoL

Preceding treatment

Chemotherapy

21-day cycle for 6 or more cycles


Regimen variant #8, q3wk AUC 7/175

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Aravantinos et al. 2005 1995-1999 Phase 3 (C) CP/Cisplatin & Paclitaxel Did not meet primary endpoint of OS
Aravantinos et al. 2008 1999-2004 Phase 3 (C) Cisplatin, Doxorubicin, Paclitaxel Might have inferior PFS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #9, q3wk AUC 7.5/175

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ozols et al. 2003 (GOG 158) NR Phase 3 (E-switch-ic) Cisplatin & Paclitaxel Seems to have non-inferior RFS

Chemotherapy

Supportive therapy

21-day cycle for 6 cycles

References

  1. Neijt JP, Engelholm SA, Tuxen MK, Sorensen PG, Hansen M, Sessa C, de Swart CA, Hirsch FR, Lund B, van Houwelingen HC. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3084-92. link to original article contains dosing details in manuscript PubMed
  2. GOG 158: Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. 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 Sep 1;21(17):3194-200. Epub 2003 Jul 14. link to original article contains dosing details in manuscript PubMed
  3. AGO-OVAR 3: du Bois A, Lück HJ, Meier W, Adams HP, Möbus V, Costa S, Bauknecht T, Richter B, Warm M, Schröder W, Olbricht S, Nitz U, Jackisch C, Emons G, Wagner U, Kuhn W, Pfisterer J; Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003 Sep 3;95(17):1320-9. link to original article contains dosing details in manuscript PubMed
  4. SCOTROC-1: Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. link to original article contains dosing details in manuscript PubMed NCT00003998
  5. Aravantinos G, Fountzilas G, Kosmidis P, Dimopoulos MA, Stathopoulos GP, Pavlidis N, Bafaloukos D, Papadimitriou C, Karpathios S, Georgoulias V, Papakostas P, Kalofonos HP, Grimani E, Skarlos DV; Hellenic Cooperative Oncology Group. Paclitaxel plus carboplatin versus paclitaxel plus alternating carboplatin and cisplatin for initial treatment of advanced ovarian cancer: long-term efficacy results: a Hellenic Cooperative Oncology Group (HeCOG) study. Ann Oncol. 2005 Jul;16(7):1116-22. Epub 2005 May 31. link to original article contains dosing details in abstract PubMed
  6. AGO-OVAR 5: du Bois A, Weber B, Rochon J, Meier W, Goupil A, Olbricht S, Barats JC, Kuhn W, Orfeuvre H, Wagner U, Richter B, Lueck HJ, Pfisterer J, Costa S, Schroeder W, Kimmig R, Pujade-Lauraine E; Arbeitsgemeinschaft Gynaekologische Onkologie; Ovarian Cancer Study Group; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens. Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens. J Clin Oncol. 2006 Mar 1;24(7):1127-35. link to original article contains dosing details in abstract PubMed
  7. HIDOC-EIS: Möbus V, Wandt H, Frickhofen N, Bengala C, Champion K, Kimmig R, Ostermann H, Hinke A, Ledermann JA; AGO-OVAR; AIO; EBMT. Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol. 2007 Sep 20;25(27):4187-93. Epub 2007 Aug 13. link to original article contains dosing details in manuscript PubMed NCT00004921
  8. MITO-2: Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00326456
    1. Update: Pignata S, Scambia G, Ferrandina G, Savarese A, Sorio R, Breda E, Gebbia V, Musso P, Frigerio L, Del Medico P, Lombardi AV, Febbraro A, Scollo P, Ferro A, Tamberi S, Brandes A, Ravaioli A, Valerio MR, Aitini E, Natale D, Scaltriti L, Greggi S, Pisano C, Lorusso D, Salutari V, Legge F, Di Maio M, Morabito A, Gallo C, Perrone F. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol. 2011 Sep 20;29(27):3628-35. Epub 2011 Aug 15. link to original article contains dosing details in manuscript PubMed
  9. GRACES: Alberts DS, Marth C, Alvarez RD, Johnson G, Bidzinski M, Kardatzke DR, Bradford WZ, Loutit J, Kirn DH, Clouser MC, Markman M; GRACES Clinical Trial Consortium. Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas: results from a prospectively designed analysis of progression-free survival. Gynecol Oncol. 2008 May;109(2):174-81. Epub 2008 Mar 7. link to original article PubMed
  10. Lhommé C, Joly F, Walker JL, Lissoni AA, Nicoletto MO, Manikhas GM, Baekelandt MM, Gordon AN, Fracasso PM, Mietlowski WL, Jones GJ, Dugan MH. Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer. J Clin Oncol. 2008 Jun 1;26(16):2674-82. link to original article contains dosing details in manuscript PubMed
  11. Aravantinos G, Fountzilas G, Bamias A, Grimani I, Rizos S, Kalofonos HP, Skarlos DV, Economopoulos T, Kosmidis PA, Stathopoulos GP, Briasoulis E, Pectasides D, Samantas E, Timotheadou E, Papadimitriou C, Papanikolaou A, Onyenadum A, Papakostas P, Bafaloukos D, Dimopoulos MA; Hellenic Cooperative Oncology Group. Carboplatin and paclitaxel versus cisplatin, paclitaxel and doxorubicin for first-line chemotherapy of advanced ovarian cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Eur J Cancer. 2008 Oct;44(15):2169-77. Epub 2008 Aug 6. link to original article contains dosing details in abstract PubMed
  12. ICON5: Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, Colombo N, Fowler JM, Argenta PA, De Geest K, Mutch DG, Burger RA, Swart AM, Trimble EL, Accario-Winslow C, Roth LM; Gynecologic Cancer Intergroup. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a phase III trial of the Gynecologic Cancer Intergroup. J Clin Oncol. 2009 Mar 20;27(9):1419-25. Epub 2009 Feb 17. Erratum in: J Clin Oncol. 2009 May 1;27(13):2305. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00011986
  13. JGOG 3016: Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, Tsuda H, Sugiyama T, Kodama S, Kimura E, Ochiai K, Noda K; Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. Epub 2009 Sep 18. link to original article contains dosing details in manuscript PubMed NCT00226915
    1. Update: Katsumata N, Yasuda M, Isonishi S, Takahashi F, Michimae H, Kimura E, Aoki D, Jobo T, Kodama S, Terauchi F, Sugiyama T, Ochiai K; Japanese Gynecologic Oncology Group. 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 Sep;14(10):1020-6. Epub 2013 Aug 13. link to original article PubMed
  14. AGO-OVAR 9: du Bois A, Herrstedt J, Hardy-Bessard AC, Müller HH, Harter P, Kristensen G, Joly F, Huober J, Avall-Lundqvist E, Weber B, Kurzeder C, Jelic S, Pujade-Lauraine E, Burges A, Pfisterer J, Gropp M, Staehle A, Wimberger P, Jackisch C, Sehouli J. Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer. J Clin Oncol. 2010 Sep 20;28(27):4162-9. Epub 2010 Aug 23. link to original article contains dosing details in abstract PubMed NCT00052468
  15. EORTC 55971: Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; EORTC-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. link to original article contains dosing details in supplement PubMed NCT00003636
  16. EORTC 55012: Hoskins P, Vergote I, Cervantes A, Tu D, Stuart G, Zola P, Poveda A, Provencher D, Katsaros D, Ojeda B, Ghatage P, Grimshaw R, Casado A, Elit L, Mendiola C, Sugimoto A, D'Hondt V, Oza A, Germa JR, Roy M, Brotto L, Chen D, Eisenhauer EA. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel. J Natl Cancer Inst. 2010 Oct 20;102(20):1547-56. Epub 2010 Oct 11. link to original article contains dosing details in abstract PubMed NCT00028743
  17. Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. link to original article contains dosing details in manuscript PubMed
  18. GOG-0218: 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; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. link to original article contains dosing details in manuscript PubMed NCT00262847
    1. PRO analysis: Monk BJ, Huang HQ, Burger RA, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Liang SX, Wenzel L. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2013 Mar;128(3):573-8. Epub 2012 Dec 4. link to original article link to PMC article PubMed
    2. Update: Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. Epub 2019 Jun 19. link to original article link to PMC article PubMed
  19. ICON7: 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, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. link to original article contains dosing details in manuscript PubMed NCT00483782
    1. QoL analysis: Stark D, Nankivell M, Pujade-Lauraine E, Kristensen G, Elit L, Stockler M, Hilpert F, Cervantes A, Brown J, Lanceley A, Velikova G, Sabate E, Pfisterer J, Carey MS, Beale P, Qian W, Swart AM, Oza A, Perren T. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol. 2013 Mar;14(3):236-43. Epub 2013 Jan 18. link to original article link to PMC article PubMed
    2. Update: 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 MK, Perren TJ; ICON. 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 Aug;16(8):928-36. Epub 2015 Jun 23. link to original article link to PMC article PubMed
  20. EORTC 55981: Lindemann K, Christensen RD, Vergote I, Stuart G, Izquierdo MA, Kærn J, Havsteen H, Eisenhauer E, Ridderheim M, Lopez AB, Hirte H, Aavall-Lundquvist E, Vrdoljak E, Green J, Kristensen GB; Gynecologic Cancer Intergroup. First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a Gynecologic Cancer Intergroup study of the NSGO, EORTC GCG and NCIC-CTG. Ann Oncol. 2012 Oct;23(10):2613-9. Epub 2012 Apr 26. link to original article contains dosing details in abstract PubMed NCT00004934
  21. MITO-7: Pignata S, Scambia G, Katsaros D, Gallo C, Pujade-Lauraine E, De Placido S, Bologna A, Weber B, Raspagliesi F, Panici PB, Cormio G, Sorio R, Cavazzini MG, Ferrandina G, Breda E, Murgia V, Sacco C, Cinieri S, Salutari V, Ricci C, Pisano C, Greggi S, Lauria R, Lorusso D, Marchetti C, Selvaggi L, Signoriello S, Piccirillo MC, Di Maio M, Perrone F; MITO; GINECO; Mario Negri Gynecologic Oncology (MaNGO); European Network of Gynaecological Oncological Trial Groups; Gynecologic Cancer Intergroup. 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 Apr;15(4):396-405. Epub 2014 Feb 28. link to original article PubMed NCT00660842
  22. CHORUS: Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, Luesley D, Perren T, Bannoo S, Mascarenhas M, Dobbs S, Essapen S, Twigg J, Herod J, McCluggage G, Parmar M, Swart AM. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015 Jul 18;386(9990):249-57. Epub 2015 May 19. link to original article contains dosing details in abstract PubMed ISRCTN74802813
  23. AGO-OVAR 12: 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, Bjørge L, Lortholary A, Sailer MO, Merger M, Harter P; AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium. 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 Jan;17(1):78-89. Epub 2015 Nov 16. link to original article contains dosing details in manuscript PubMed NCT01015118
    1. Update: Ray-Coquard I, Cibula D, Mirza MR, Reuss A, Ricci C, Colombo N, Koch H, Goffin F, González-Martin A, Ottevanger PB, Baumann K, Bjørge L, Lesoin A, Burges A, Rosenberg P, Gropp-Meier M, Harrela M, Harter P, Frenel JS, Minarik T, Pisano C, Hasenburg A, Merger M, du Bois A; AGO Study Group-led GCIG/ENGOT Intergroup Consortium. Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer. Int J Cancer. 2020 Jan 15;146(2):439-448. Epub 2019 Sep 6. link to original article PubMed
  24. GOG-0262: 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 Feb 25;374(8):738-48. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01167712
  25. SCORPION: Fagotti A, Ferrandina G, Vizzielli G, Fanfani F, Gallotta V, Chiantera V, Costantini B, Margariti PA, Gueli Alletti S, Cosentino F, Tortorella L, Scambia G. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): final analysis of peri-operative outcome. Eur J Cancer. 2016 May;59:22-33. Epub 2016 Mar 19. link to original article contains dosing details in manuscript PubMed NCT01461850
  26. JGOG3017: Sugiyama T, Okamoto A, Enomoto T, Hamano T, Aotani E, Terao Y, Suzuki N, Mikami M, Yaegashi N, Kato K, Yoshikawa H, Yokoyama Y, Tanabe H, Nishino K, Nomura H, Kim JW, Kim BG, Pignata S, Alexandre J, Green J, Isonishi S, Terauchi F, Fujiwara K, Aoki D. Randomized phase III trial of irinotecan plus cisplatin compared with paclitaxel plus carboplatin as first-line chemotherapy for ovarian clear cell carcinoma: JGOG3017/GCIG trial. J Clin Oncol. 2016 Aug 20;34(24):2881-7. Epub 2016 Jul 11. link to original article contains dosing details in abstract PubMed UMIN000000499
  27. TRINOVA-3: Vergote I, Scambia G, O'Malley DM, Van Calster B, Park SY, Del Campo JM, Meier W, Bamias A, Colombo N, Wenham RM, Covens A, Marth C, Raza Mirza M, Kroep JR, Ma H, Pickett CA, Monk BJ; TRINOVA-3/ENGOT-ov2/GOG-3001 investigators. Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):862-876. Epub 2019 May 7. link to original article contains dosing details in abstract PubMed NCT01493505
  28. VELIA: Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA 3rd, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2403-2415. Epub 2019 Sep 28. link to original article link to PMC article PubMed NCT02470585
  29. ICON8: Clamp AR, James EC, McNeish IA, Dean A, Kim JW, O'Donnell DM, Hook J, Coyle C, Blagden S, Brenton JD, Naik R, Perren T, Sundar S, Cook AD, Gopalakrishnan GS, Gabra H, Lord R, Dark G, Earl HM, Hall M, Banerjee S, Glasspool RM, Jones R, Williams S, Swart AM, Stenning S, Parmar M, Kaplan R, Ledermann JA. 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 Dec 7;394(10214):2084-2095. Epub 2019 Nov 29. link to original article contains dosing details in abstract link to PMC article PubMed NCT01654146
    1. Update: Clamp AR, James EC, McNeish IA, Dean A, Kim JW, O'Donnell DM, Gallardo-Rincon D, Blagden S, Brenton J, Perren TJ, Sundar S, Lord R, Dark G, Hall M, Banerjee S, Glasspool RM, Hanna CL, Williams S, Scatchard KM, Nam H, Essapen S, Parkinson C, McAvan L, Swart AM, Popoola B, Schiavone F, Badrock J, Fananapazir F, Cook AD, Parmar M, Kaplan R, Ledermann JA. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2022 Jul;23(7):919-930. Epub 2022 Jun 8. link to original article link to PMC article PubMed
  30. JAVELIN Ovarian 100: Monk BJ, Colombo N, Oza AM, Fujiwara K, Birrer MJ, Randall L, Poddubskaya EV, Scambia G, Shparyk YV, Lim MC, Bhoola SM, Sohn J, Yonemori K, Stewart RA, Zhang X, Perkins Smith J, Linn C, Ledermann JA. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Sep;22(9):1275-1289. Epub 2021 Aug 4. link to original article contains dosing details in abstract PubMed NCT02718417
  31. FLORA-5: NCT04498117
  32. KEYLYNK-001: NCT03740165

Carboplatin & Paclitaxel (CP) & Bevacizumab

TC-BEV: Taxol (Paclitaxel), Carboplatin, BEVacizumab

Regimen variant #1, q3wk paclitaxel, standard-dose bevacizumab x 6

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Burger et al. 2011 (GOG-0218) 2005-2009 Phase 3 (E-RT-esc) 1. Carboplatin & Paclitaxel Might have superior PFS (primary endpoint)
Median PFS: 11.2 vs 10.3 mo
(HR 0.91, 95% CI 0.80-1.04)

Did not meet secondary endpoint of OS1
Median OS: 40.8 vs 41.1 mo
(HR 1.06, 95% CI 0.94-1.20)
2. CP & Bevacizumab x 22 Not reported
Chan et al. 2016 (GOG-0262) 2010-2012 Phase 3 (C) TC-Bev; dose-dense Did not meet primary endpoint of PFS
Moore et al. 2021 (IMagyn050) 2017-2019 Phase 3 (C) CP, Atezolizumab, Bevacizumab Did not meet primary endpoint of PFS

1Reported efficacy for OS in this arm of GOG-0218 is based on the 2019 update.
Note: Decision to use bevacizumab in GOG-0262 was at the discretion of the patient; it was not a randomization.

Chemotherapy

Targeted therapy

21-day cycle for 6 cycles

Subsequent treatment


Regimen variant #2, q3wk paclitaxel, standard-dose bevacizumab x 22

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Burger et al. 2011 (GOG-0218)
ESMO-MCBS (3)
2005-2009 Phase 3 (E-RT-esc) 1. Carboplatin & Paclitaxel Superior PFS (primary endpoint)
Median PFS: 14.1 vs 10.3 mo
(HR 0.72, 95% CI 0.625-0.82)

Did not meet secondary endpoint of OS1
Median OS: 43.4 vs 41.1 mo
(HR 0.96, 95% CI 0.85-1.09)
2. CP & Bevacizumab x 6 Not reported

1Reported efficacy for OS in this arm of GOG-0218 is based on the 2019 update.

Chemotherapy

Targeted therapy

21-day cycle for 22 cycles


Regimen variant #3, q3wk paclitaxel, low-dose bevacizumab

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Perren et al. 2011 (ICON7)
ESMO-MCBS (1)
2006-2009 Phase 3 (E-esc) Carboplatin & Paclitaxel Did not meet primary endpoints of PFS/OS1

1Reported efficacy is based on the 2015 update.
Note: Bevacizumab is not given with cycle 1 if chemotherapy starts within 4 weeks of surgery.

Chemotherapy

  • Carboplatin (Paraplatin) as follows:
    • Cycles 1 to 6: AUC 5 to 6 IV over 30 to 60 minutes once on day 1
      • The protocol linked from Perren et al. 2011 clarifies that the recommended dose was AUC 6, but that it could be adjusted per standard practice
  • Paclitaxel (Taxol) as follows:
    • Cycles 1 to 6: 175 mg/m2 IV over 3 hours once on day 1

Targeted therapy

  • Bevacizumab (Avastin) as follows:
    • Cycles 1 to 6: 7.5 mg/kg IV once on day 1
    • Cycles 7 to 18: 15 mg/kg IV once on day 1

21-day cycle for 18 cycles


Regimen variant #4, weekly paclitaxel

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Walker et al. 2019 (GOG-252) 2009-2011 Phase 3 (C) 1. IP Carboplatin, IV Paclitaxel, Bevacizumab
2. IP Cisplatin, IV/IP Paclitaxel, Bevacizumab 		Did not meet primary endpoint of PFS

Chemotherapy

Targeted therapy

21-day cycle for 6 cycles

Subsequent treatment

References

  1. GOG-0218: 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; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. link to original article contains dosing details in manuscript PubMed NCT00262847
    1. PRO analysis: Monk BJ, Huang HQ, Burger RA, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Liang SX, Wenzel L. Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2013 Mar;128(3):573-8. Epub 2012 Dec 4. link to original article link to PMC article PubMed
    2. Update: Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. Epub 2019 Jun 19. link to original article link to PMC article PubMed
  2. ICON7: 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, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. link to original article contains dosing details in manuscript PubMed NCT00483782
    1. QoL analysis: Stark D, Nankivell M, Pujade-Lauraine E, Kristensen G, Elit L, Stockler M, Hilpert F, Cervantes A, Brown J, Lanceley A, Velikova G, Sabate E, Pfisterer J, Carey MS, Beale P, Qian W, Swart AM, Oza A, Perren T. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol. 2013 Mar;14(3):236-43. Epub 2013 Jan 18. link to original article link to PMC article PubMed
    2. Update: 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 MK, Perren TJ; ICON. 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 Aug;16(8):928-36. Epub 2015 Jun 23. link to original article link to PMC article PubMed
  3. GOG-0262: 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 Feb 25;374(8):738-48. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01167712
  4. GOG-252: Walker JL, Brady MF, Wenzel L, Fleming GF, Huang HQ, DiSilvestro PA, Fujiwara K, Alberts DS, Zheng W, Tewari KS, Cohn DE, Powell MA, Van Le L, Davidson SA, Gray HJ, Rose PG, Aghajanian C, Myers T, Alvarez Secord A, Rubin SC, Mannel RS. Randomized trial of intravenous versus intraperitoneal chemotherapy plus bevacizumab in advanced ovarian carcinoma: An NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2019 Jun 1;37(16):1380-1390. Epub 2019 Apr 19. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00951496
  5. IMagyn050: Moore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, Myers T, Taskiran C, Robison K, Mäenpää J, Willmott L, Colombo N, Thomes-Pepin J, Liontos M, Gold MA, Garcia Y, Sharma SK, Darus CJ, Aghajanian C, Okamoto A, Wu X, Safin R, Wu F, Molinero L, Maiya V, Khor VK, Lin YG, Pignata S. Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol. 2021 Jun 10;39(17):1842-1855. Epub 2021 Apr 23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT03038100
  6. FIRSTOV: NCT03602859

Carboplatin & Paclitaxel (CP) & Nintedanib

CP & Nintedanib: Carboplatin, Paclitaxel, Nintedanib
TC & Nintedanib: Taxol (Paclitaxel), Carboplatin, Nintedanib

Regimen variant #1, q3wk AUC 5/175

Study Dates of enrollment Evidence Comparator Comparative Efficacy
du Bois et al. 2015 (AGO-OVAR 12) 2009-2011 Phase 3 (E-esc) TC Seems to have superior PFS
Median PFS: 17.2 vs 16.6 mo
(HR 0.84, 95% CI 0.72-0.98)

Preceding treatment

Chemotherapy

Targeted therapy

21-day cycles


Regimen variant #2, q3wk AUC 6/175

Study Dates of enrollment Evidence Comparator Comparative Efficacy
du Bois et al. 2015 (AGO-OVAR 12) 2009-2011 Phase 3 (E-esc) TC Seems to have superior PFS
Median PFS: 17.2 vs 16.6 mo
(HR 0.84, 95% CI 0.72-0.98)

Preceding treatment

Chemotherapy

Targeted therapy

21-day cycles

References

  1. AGO-OVAR 12: 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, Bjørge L, Lortholary A, Sailer MO, Merger M, Harter P; AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium. 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 Jan;17(1):78-89. Epub 2015 Nov 16. link to original article contains dosing details in manuscript PubMed NCT01015118
    1. Update: Ray-Coquard I, Cibula D, Mirza MR, Reuss A, Ricci C, Colombo N, Koch H, Goffin F, González-Martin A, Ottevanger PB, Baumann K, Bjørge L, Lesoin A, Burges A, Rosenberg P, Gropp-Meier M, Harrela M, Harter P, Frenel JS, Minarik T, Pisano C, Hasenburg A, Merger M, du Bois A; AGO Study Group-led GCIG/ENGOT Intergroup Consortium. Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer. Int J Cancer. 2020 Jan 15;146(2):439-448. Epub 2019 Sep 6. link to original article PubMed

Cisplatin & Paclitaxel

TP: Taxol (Paclitaxel) & Platinol (Cisplatin)
PT: Platinol (Cisplatin) & Taxol (Paclitaxel)

Regimen variant #1, 75/135

Study Dates of enrollment Evidence Comparator Comparative Efficacy
McGuire et al. 1996 (GOG 111) NR Phase 3 (E-RT-switch-ic) Cisplatin & Cyclophosphamide Superior OS
Median OS: 38 vs 24 mo
(RR 0.60, 95% CI 0.50-0.80)
Muggia et al. 2000 (GOG 132) 1992-1994 Phase 3 (C) 1. Cisplatin
2. Paclitaxel 		Did not meet primary endpoint of PFS
Markman et al. 2001 (GOG 114) 1992-1995 Phase 3 (C) Carboplatin, then IP Cisplatin & IV Paclitaxel Seems to have inferior OS
Ozols et al. 2003 (GOG 158) NR Phase 3 (C) Carboplatin & Paclitaxel Seems to have non-inferior RFS
Rose et al. 2004 (GOG 152) 1994-2001 Phase 3 (C) Cisplatin & Paclitaxel; with interval debulking Did not meet primary endpoint of OS
Armstrong et al. 2006 (GOG 172) 1998-2001 Phase 3 (C) Cisplatin & Paclitaxel; IP Seems to have inferior OS
Spriggs et al. 2007 (GOG 162) NR Phase 3 (C) Cisplatin & Paclitaxel; prolonged-infusion paclitaxel Did not meet primary endpoint of OS

Preceding treatment

Chemotherapy

  • Cisplatin (Platinol) 75 mg/m2 IV once on day 1
    • Some regimens give the cisplatin after the paclitaxel (i.e., on day 2)
  • Paclitaxel (Taxol) 135 mg/m2 IV continuous infusion over 24 hours, started on day 1

Supportive therapy

  • (details vary depending on reference):
  • Dexamethasone (Decadron) with one of the following options:
    • 20 mg PO twice on day 1; 12 and 6 hours prior to chemotherapy
    • 20 mg IV once on day 1; 30 minutes prior to paclitaxel
  • Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
  • Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
  • "Hydration and antiemetic agents" once on day 1, prior to cisplatin

21-day cycle for 6 cycles


Regimen variant #2, 75/175

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Piccart et al. 2000 (OV10) 1994-1995 Phase 3 (E-RT-switch-ic) Cisplatin & Cyclophosphamide Superior OS
Neijt et al. 2000 1994-1997 Phase 3 (C) Carboplatin & Paclitaxel Did not meet primary endpoint of PFS
Mouratidou et al. 2007 1998-2002 Phase 3 (E-switch-ic) Cisplatin & Cyclophosphamide Did not meet primary endpoint of PFS
van der Burg et al. 2014 1999-2006 Phase 3 (C) Cisplatin & Paclitaxel; weekly paclitaxel Did not meet primary endpoint of PFS

Preceding treatment

Chemotherapy

21-day cycle for 6 or more cycles


Regimen variant #3, 75/185

Study Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
du Bois et al. 2003 (AGO-OVAR 3) 1995-1997 Phase 3 (C) Carboplatin & Paclitaxel Non-inferior PFS Inferior QoL

Preceding treatment

Chemotherapy

  • Cisplatin (Platinol) 75 mg/m2 (maximum dose of 165 mg) IV over 30 minutes once on day 1, given second
  • Paclitaxel (Taxol) 185 mg/m2 (maximum dose of 400 mg) IV over 3 hours once on day 1, given first

21-day cycle for 6 or more cycles

References

  1. GOG 111: McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 1996 Jan 4;334(1):1-6. link to original article contains dosing details in manuscript PubMed
  2. GOG 132: Muggia FM, Braly PS, Brady MF, Sutton G, Niemann TH, Lentz SL, Alvarez RD, Kucera PR, Small JM. Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2000 Jan;18(1):106-15. link to original article contains dosing details in manuscript PubMed
  3. OV10: Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, Stuart G, Kaye S, Vergote I, Blom R, Grimshaw R, Atkinson RJ, Swenerton KD, Trope C, Nardi M, Kaern J, Tumolo S, Timmers P, Roy JA, Lhoas F, Lindvall B, Bacon M, Birt A, Andersen JE, Zee B, Paul J, Baron B, Pecorelli S. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst. 2000 May 3;92(9):699-708. link to original article contains dosing details in manuscript PubMed
  4. Neijt JP, Engelholm SA, Tuxen MK, Sorensen PG, Hansen M, Sessa C, de Swart CA, Hirsch FR, Lund B, van Houwelingen HC. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3084-92. link to original article contains dosing details in manuscript PubMed
  5. GOG 114: Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. 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 Feb 15;19(4):1001-7. link to original article contains dosing details in abstract PubMed
  6. GOG 158: Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R; Gynecologic Oncology Group. 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 Sep 1;21(17):3194-200. Epub 2003 Jul 14. link to original article contains dosing details in manuscript PubMed
  7. AGO-OVAR 3: du Bois A, Lück HJ, Meier W, Adams HP, Möbus V, Costa S, Bauknecht T, Richter B, Warm M, Schröder W, Olbricht S, Nitz U, Jackisch C, Emons G, Wagner U, Kuhn W, Pfisterer J; Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003 Sep 3;95(17):1320-9. link to original article contains dosing details in manuscript PubMed
  8. GOG 152: Rose PG, Nerenstone S, Brady MF, Clarke-Pearson D, Olt G, Rubin SC, Moore DH, Small JM; Gynecologic Oncology Group. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. 2004 Dec 9;351(24):2489-97. link to original article contains dosing details in manuscript PubMed NCT00002568
  9. GOG 172: Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. link to original article contains dosing details in manuscript PubMed NCT00003322
    1. Subgroup analysis: Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke-Pearson D. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jan;100(1):27-32. link to original article contains dosing details in manuscript PubMed
  10. Mouratidou D, Gennatas C, Michalaki V, Papadimitriou A, Andreadis CH, Sykiotis C, Tsavaris N. A phase III randomized study comparing paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer. Anticancer Res. 2007 Jan-Feb;27(1B):681-5. link to original article contains dosing details in abstract PubMed
  11. GOG 162: Spriggs DR, Brady MF, Vaccarello L, Clarke-Pearson DL, Burger RA, Mannel R, Boggess JF, Lee RB, Hanly M. Phase III randomized trial of intravenous cisplatin plus a 24- or 96-hour infusion of paclitaxel in epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Oct 1;25(28):4466-71. link to original article contains dosing details in abstract PubMed NCT00002717
  12. van der Burg ME, Onstenk W, Boere IA, Look M, Ottevanger PB, de Gooyer D, Kerkhofs LG, Valster FA, Ruit JB, van Reisen AG, Goey SH, van der Torren AM, ten Bokkel Huinink D, Kok TC, Verweij J, van Doorn HC. Long-term results of a randomised phase III trial of weekly versus three-weekly paclitaxel/platinum induction therapy followed by standard or extended three-weekly paclitaxel/platinum in European patients with advanced epithelial ovarian cancer. Eur J Cancer. 2014 Oct;50(15):2592-601. Epub 2014 Aug 2. link to original article contains dosing details in abstract PubMed

Intraperitoneal therapy

Cisplatin & Paclitaxel

Regimen variant #1, IV paclitaxel

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Markman et al. 2001 (GOG 114) 1992-1995 Phase 3 (E-switch-ic) See link See link

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #2, IV/IP paclitaxel

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Armstrong et al. 2006 (GOG 172) 1998-2001 Phase 3 (E-switch-ic) Cisplatin & Paclitaxel; IV Seems to have superior OS

Chemotherapy

  • Cisplatin (Platinol) 100 mg/m2 IP rapid infusion once on day 2
    • Walker et al. 2006 instructs that the patient be rolled onto 4 different positions every 15 minutes to evenly distribute cisplatin
  • Paclitaxel (Taxol) 135 mg/m2 IV continuous infusion over 24 hours, started on day 1, then 60 mg/m2 IP rapid infusion once on day 8

Supportive therapy

  • (Varies per reference)
  • "Standard premedication" for paclitaxel
  • "Hydration and antiemetic agents" prior to cisplatin
  • Intraperitoneal doses of cisplatin and paclitaxel are reconstituted in 2 liters of warm normal saline before infusion
  • Additional 1 liter normal saline to be infused immediately after intraperitoneal paclitaxel
  • Supportive medications left to investigator discretion

21-day cycle for 6 cycles

References

  1. GOG 114: Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. 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 Feb 15;19(4):1001-7. link to original article contains dosing details in abstract PubMed
  2. GOG 172: Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. link to original article contains dosing details in manuscript PubMed NCT00003322
    1. Subgroup analysis: Walker JL, Armstrong DK, Huang HQ, Fowler J, Webster K, Burger RA, Clarke-Pearson D. Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2006 Jan;100(1):27-32. link to original article contains dosing details in manuscript PubMed

Maintenance after first-line therapy

Altretamine monotherapy

Regimen

Study Dates of enrollment Evidence
Rothenberg et al. 2001 (SWOG-9326) 1993-1997 Phase 2

Chemotherapy

28-day cycle for 6 cycles

References

  1. SWOG-9326: Rothenberg ML, Liu PY, Wilczynski S, Hannigan EV, Weiner SA, Weiss GR, Hunter VJ, Chapman JA, Tiersten A, Kohler PC, Alberts DS. Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326). Gynecol Oncol. 2001 Aug;82(2):317-22. link to original article contains dosing details in abstract PubMed
    1. Update: Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. link to original article PubMed

Bevacizumab monotherapy

Regimen variant #1, 16 cycles

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Walker et al. 2019 (GOG-252) 2009-2011 Non-randomized part of RCT
Pfisterer et al. 2023 (BOOST) 2011-11-11 to 2013-08-06 Phase 3 (C) Bevacizumab x 30 mo Did not meet primary endpoint of PFS
Ray-Coquard et al. 2019 (PAOLA-1) 2015-2017 Phase 3 (C) Olaparib & Bevacizumab Inferior PFS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of treatment is 22 cycles (including the 6 cycles of combination chemotherapy).

Preceding treatment

Targeted therapy

21-day cycle for up to 16 cycles


Regimen variant #2, indefinite

Study Dates of enrollment Evidence
Chan et al. 2016 (GOG-0262) 2010-2012 Non-randomized part of RCT

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Preceding treatment

Targeted therapy

21-day cycles

References

  1. GOG-0262: 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 Feb 25;374(8):738-48. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01167712
  2. GOG-252: Walker JL, Brady MF, Wenzel L, Fleming GF, Huang HQ, DiSilvestro PA, Fujiwara K, Alberts DS, Zheng W, Tewari KS, Cohn DE, Powell MA, Van Le L, Davidson SA, Gray HJ, Rose PG, Aghajanian C, Myers T, Alvarez Secord A, Rubin SC, Mannel RS. Randomized trial of intravenous versus intraperitoneal chemotherapy plus bevacizumab in advanced ovarian carcinoma: An NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2019 Jun 1;37(16):1380-1390. Epub 2019 Apr 19. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00951496
  3. PAOLA-1: Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. link to original article contains dosing details in manuscript PubMed NCT02477644
  4. BOOST: Pfisterer J, Joly F, Kristensen G, Rau J, Mahner S, Pautier P, El-Balat A, Kurtz JE, Canzler U, Sehouli J, Heubner ML, Hartkopf AD, Baumann K, Hasenburg A, Hanker LC, Belau A, Schmalfeldt B, Denschlag D, Park-Simon TW, Selle F, Jackisch C, Burges A, Lueck HJ, Emons G, Meier W, Gropp-Meier M, Schroeder W, de Gregorio N, Hilpert F, Harter P. Optimal Treatment Duration of Bevacizumab as Front-Line Therapy for Advanced Ovarian Cancer: AGO-OVAR 17 BOOST/GINECO OV118/ENGOT Ov-15 Open-Label Randomized Phase III Trial. J Clin Oncol. 2023 Feb 1;41(4):893-902. Epub 2022 Nov 4. link to original article PubMed NCT01462890

Niraparib monotherapy

Regimen variant #1, 200 mg/day

Study Dates of enrollment Evidence Comparator Comparative Efficacy
González-Martín et al. 2019 (PRIMAOV)
ESMO-MCBS (3)
2016-2018 Phase 3 (E-RT-esc) Placebo Superior PFS1 (primary endpoint)
Median PFS: 13.8 vs 8.2 mo
(HR 0.62, 95% CI 0.50-0.76)

1Reported efficacy is for the overall population.
Note: this dose was used for patients with body weight of less than 77 kg or a platelet count of less than 150 x 109/L.

Preceding treatment

Targeted therapy

28-day cycle for up to 39 cycles (3 years)


Regimen variant #2, 300 mg/day

Study Dates of enrollment Evidence Comparator Comparative Efficacy
González-Martín et al. 2019 (PRIMAOV)
ESMO-MCBS (3)
2016-2018 Phase 3 (E-RT-esc) Placebo Superior PFS1 (primary endpoint)
Median PFS: 13.8 vs 8.2 mo
(HR 0.62, 95% CI 0.50-0.76)

1Reported efficacy is for the overall population.

Preceding treatment

Targeted therapy

28-day cycle for up to 39 cycles (3 years)

References

  1. 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 PubMed NCT02655016

Olaparib & Bevacizumab

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ray-Coquard et al. 2019 (PAOLA-1)
ESMO-MCBS (3)
2015-2017 Phase 3 (E-RT-esc) Bevacizumab Superior PFS (primary endpoint)
Median PFS: 22.1 vs 16.6 mo
(HR 0.59, 95% CI 0.49-0.72)

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of bevacizumab treatment is 22 cycles (including the 6 cycles of combination chemotherapy).

Preceding treatment

  • Not specified, but presumably platinum doublet & bevacizumab x 6; olaparib is started between 3 and 9 weeks after last chemotherapy dose.

Targeted therapy

21-day cycle for up to 35 cycles (2 years)

References

  1. PAOLA-1: Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. link to original article contains dosing details in manuscript PubMed NCT02477644

Paclitaxel monotherapy

Regimen variant #1, 135 mg/m2 q4wk

Study Dates of enrollment Evidence
Gordon et al. 2011 2002-2006 Non-randomized part of RCT

Preceding treatment

Chemotherapy

28-day cycle for up to 12 cycles


Regimen variant #2, 175 mg/m2 q3wk x 3

Study Dates of enrollment Evidence
Micha et al. 2005 2002-07 to 2003-08 Phase 2, <20 patients in this subgroup

Preceding treatment

Chemotherapy

21-day cycle for 3 cycles


Regimen variant #3, 175 mg/m2 q3wk x 12

Study Dates of enrollment Evidence
Micha et al. 2005 2002-07 to 2003-08 Phase 2, <20 patients in this subgroup

Preceding treatment

Chemotherapy

21-day cycle for 12 cycles


Regimen variant #4, 175 mg/m2 q4wk x 3

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Markman et al. 2003 (GOG 178) 1997-2001 Phase 3 (C) Paclitaxel x 12 Inferior PFS

Chemotherapy

28-day cycle for 3 cycles


Regimen variant #5, 175 mg/m2 q4wk x 12

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Markman et al. 2003 (GOG 178) 1997-2001 Phase 3 (E-esc) Paclitaxel x 3 Superior PFS

Chemotherapy

28-day cycle for 12 cycles

References

  1. GOG 178: Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D; SWOG; Gynecologic Oncology Group. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol. 2003 Jul 1;21(13):2460-5. link to original article contains dosing details in manuscript PubMed NCT00003120
    1. Update: Markman M, Liu PY, Moon J, Monk BJ, Copeland L, Wilczynski S, Alberts D. 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 Aug;114(2):195-8. Epub 2009 May 17. link to original article contains dosing details in manuscript link to PMC article PubMed
  2. Micha JP, Goldstein BH, Mattison JA, Bader K, Graham C, Rettenmaier MA, Brown JV, Markman M. Experience with single-agent paclitaxel consolidation following primary chemotherapy with carboplatin, paclitaxel, and gemcitabine in advanced ovarian cancer. Gynecol Oncol. 2005 Jan;96(1):132-5. link to original article contains dosing details in manuscript PubMed
  3. Retrospective: Abaid LN, Goldstein BH, Micha JP, Rettenmaier MA, Brown JV 3rd, Markman M. Improved overall survival with 12 cycles of single-agent paclitaxel maintenance therapy following a complete response to induction chemotherapy in advanced ovarian carcinoma. Oncology. 2010;78(5-6):389-93. Epub 2010 Aug 27. link to original article contains dosing details in manuscript PubMed
  4. Gordon AN, Teneriello M, Janicek MF, Hines J, Lim PC, Chen MD, Vaccarello L, Homesley HD, McMeekin S, Burkholder TL, Wang Y, Zhao L, Orlando M, Obasaju CK, Gill JF, Tai DF. Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer. Gynecol Oncol. 2011 Dec;123(3):479-85. Epub 2011 Oct 5. link to original article contains dosing details in manuscript PubMed

Pazopanib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Du Bois et al. 2014 (AGO-OVAR 16) 2009-2010 Phase 3 (E-esc) Placebo Superior PFS
Median PFS: 17.9 vs 12.3 mo
(HR 0.77, 95% CI 0.64-0.91)

Patients enrolled in AGO-OVAR 16 had histologically confirmed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, were FIGO II to IV, and no evidence of progression after initial treatment.

Preceding treatment

  • Surgery and at least 5 cycles of platinum and taxane combination chemotherapy

Targeted therapy

24-month course

References

  1. 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 contains dosing details in manuscript PubMed NCT00866697
    1. 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 PubMed
    2. 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 PubMed

Rucaparib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Monk et al. 2022 (ATHENA-MONO) 2018-2020 Phase 3 (E-esc) Placebo Superior PFS
Median PFS: 20.2 vs 9.2 mo
(HR 0.52, 95% CI 0.40-0.68)

Preceding treatment

Targeted therapy

28-day cycles

References

  1. 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 PubMed NCT03522246

Second-line therapy for relapsed or recurrent disease, platinum-sensitive

Carboplatin monotherapy

Regimen variant #1, AUC 5

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Parmar et al. 2003 (ICON4) 1996-2002 Phase 3 (C) 1a. Carboplatin & Paclitaxel
1b. Cisplatin & Paclitaxel 		Seems to have inferior OS
Pfisterer et al. 2006 (AGO-OVAR 2.5) 1999-2002 Phase 3 (C) Carboplatin & Gemcitabine Inferior PFS

Chemotherapy

21-day cycle for 6 to 10 cycles


Regimen variant #2, 300 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bolis et al. 2001 (ARGO 96) 1991-NR Phase 3 (C) Carboplatin & Epirubicin Did not meet primary endpoint of ORR

Chemotherapy

28-day cycle for 5 cycles

References

  1. ARGO 96: Bolis G, Scarfone G, Giardina G, Villa A, Mangili G, Melpignano M, Presti M, Tateo S, Franchi M, Parazzini F; Associazione per la Ricerca in Ginecologia Oncologia Study Group. Carboplatin alone vs carboplatin plus epidoxorubicin as second-line therapy for cisplatin- or carboplatin-sensitive ovarian cancer. Gynecol Oncol. 2001 Apr;81(1):3-9. link to original article contains dosing details in abstract PubMed
  2. ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. 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 Jun 21;361(9375):2099-106. link to original article contains dosing details in manuscript PubMed NCT00002894
  3. AGO-OVAR 2.5: Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC-CTG; EORTC GCG. 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 Oct 10;24(29):4699-707. Epub 2006 Sep 11. link to original article contains dosing details in manuscript PubMed NCT00102414

Carboplatin & Docetaxel

Regimen variant #1, AUC 2/35, 3 weeks out of 4

Study Dates of enrollment Evidence
Kushner et al. 2007 NR Phase 2

Note: BSA was capped at 2 m2.

Chemotherapy

Supportive therapy

28-day cycle for 6 cycles


Regimen variant #2, AUC 5/75

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Strauss et al. 2007 2000-2003 Phase 2
Vergote et al. 2016 (FAR-131) 2009-NR Phase 3 (C) 1a. CP & Farletuzumab; 1.25 mg/kg
1b. DCb & Farletuzumab; 1.25 mg/kg
2a. CP & Farletuzumab; 2.5 mg/kg
2b. DCb & Farletuzumab; 2.5 mg/kg 		Did not meet primary endpoint of PFS
Shi et al. 2021 (SOC-1) 2012-2019 Non-randomized part of phase III RCT

Note: this is the lower bound of carboplatin dosing specified by FAR-131.

Preceding treatment

Chemotherapy

Supportive therapy

21-day cycle for 6 cycles


Regimen variant #3, AUC 6/75

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vergote et al. 2016 (FAR-131) 2009-NR Phase 3 (C) 1a. CP & Farletuzumab; 1.25 mg/kg
1b. DCb & Farletuzumab; 1.25 mg/kg
2a. CP & Farletuzumab; 2.5 mg/kg
2b. DCb & Farletuzumab; 2.5 mg/kg 		Did not meet primary endpoint of PFS

Note: this is the upper bound of carboplatin dosing specified by FAR-131.

Chemotherapy

21-day cycle for 6 cycles

References

  1. Strauss HG, Henze A, Teichmann A, Karbe I, Baumgart A, Thomssen C, Koelbl H. Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Gynecol Oncol. 2007 Mar;104(3):612-6. Epub 2006 Oct 27. link to original article contains dosing details in manuscript PubMed
  2. Kushner DM, Connor JP, Sanchez F, Volk M, Schink JC, Bailey HH, Harris LS, Stewart SL, Fine J, Hartenbach EM; Wisconsin Oncology Network. Weekly docetaxel and carboplatin for recurrent ovarian and peritoneal cancer: a phase II trial. Gynecol Oncol. 2007 May;105(2):358-64. Epub 2007 Jan 29. link to original article contains dosing details in manuscript PubMed
  3. FAR-131: Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, Weil SC, Bamias A, Fujiwara K, Ochiai K, Poole C, Gorbunova V, Wang W, O'Shannessy D, Herzog TJ. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol. 2016 Jul 1;34(19):2271-8. Epub 2016 Mar 21. link to original article contains dosing details in manuscript PubMed NCT00849667
  4. SOC-1: Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, Jia H, Huang X, Cai Y, Yin S, Jiang R, Tian W, Gao W, Liu J, Yang H, Cheng X, Zang R. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):439-449. Epub 2021 Mar 8. link to original article contains dosing details in abstract PubMed NCT01611766

Carboplatin & Pegylated liposomal doxorubicin

CD: Carboplatin & Doxil (Pegylated liposomal doxorubicin)
PLDC: Pegylated Liposomal Doxorubicin & Carboplatin

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2010 (CALYPSO) 2005-2007 Phase 3 (E-switch-ic) Carboplatin & Paclitaxel Superior PFS
Median PFS: 11.3 vs 9.4 mo
(HR 0.82, 95% CI 0.72-0.94)
Sehouli et al. 2016 (HECTOR) 2007-2009 Randomized Phase 2 (C) Carboplatin & Topotecan Did not meet primary endpoint of PFS12
Colombo et al. 2023 (INOVATYON) 2011-12 to 2017-09-18 Phase 3 (C) PLD & Trabectedin Did not meet primary endpoint of OS
Pignata et al. 2021 (MITO 16) 2013-2016 Phase 3 (C) 1a. Carboplatin, PLD, Bevacizumab
1b. Carboplatin, Gemcitabine, Bevacizumab
1c. CP & Bevacizumab 		Inferior PFS
Liu et al. 2022 (NRG-GY004) 2016-02-04 to 2017-11-13 Phase 3 (C) 1. Olaparib
2. Cediranib & Olaparib 		Did not meet primary endpoint of PFS

Note: CALYPSO stands for Caelyx (Pegylated liposomal doxorubicin) in Platinum Sensitive Ovarian patients

Chemotherapy

Supportive therapy

28-day cycle for 4 or more cycles, depending on response and toxicity

References

  1. CALYPSO: Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010 Jul 10;28(20):3323-9. Epub 2010 May 24. link to original article contains dosing details in manuscript PubMed NCT00189553
    1. Update: Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Pujade Lauraine E. 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 Aug 7;107(4):588-91. Epub 2012 Jul 26. link to original article contains dosing details in manuscript link to PMC article PubMed
  2. HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article contains dosing details in manuscript PubMed NCT00437307
  3. MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains dosing details in abstract PubMed NCT01802749
  4. NRG-GY004: Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. link to original article contains dosing details in supplement link to PMC article PubMed NCT02446600
  5. INOVATYON: Colombo N, Fossati R, Gadducci A, Bologna A, Sehouli J, Rulli E, Maenpaa J, Berger R, Sessa C, Montes A, Ottevanger NB, Vergote I, D'Incalci M, Chekerov R, Nyvang GB, Riniker S, Herbertson R, Barretina-Ginesta MP, Deryal M, Mirza MR, Biagioli E, Iglesias M, Funari G, Romeo M, Churruca Galaz C, Tasca G, Pardo B, Tognon G, Rubio-Perez MJ, DeCensi A, De Giorgi U, Zola P, Benedetti Panici P, Aglietta M, Arcangeli V, Zamagni C, Westermann A, Heinzelmann-Schwarz V, Tsibulak I, Wimberger P, Poveda A. INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line. Br J Cancer. 2023 Apr;128(8):1503-1513. Epub 2023 Feb 9. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01379989

Carboplatin, Pegylated liposomal doxorubicin, Bevacizumab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pfisterer et al. 2020 (AGO-OVAR 2.21/ENGOT-ov 18) 2013-2015 Phase 3 (E-switch-ic) Carboplatin, Gemcitabine, Bevacizumab Seems to have superior PFS
Median PFS: 13.3 vs 11.6 mo
(HR 0.81, 95% CI 0.68-0.96)
Pignata et al. 2021 (MITO 16) 2013-2016 Phase 3 (E-esc) 1a. Carboplatin & PLD
1b. Carboplatin & Gemcitabine
1c. CP 		Superior PFS
Median PFS: 11.8 vs 8.8 mo
(HR 0.51, 95% CI 0.41-0.65)

Chemotherapy

Targeted therapy

28-day cycle for 6 or more cycles

Subsequent treatment

References

  1. AGO-OVAR 2.21/ENGOT-ov 18: Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. Epub 2020 Apr 16. link to original article contains dosing details in abstract PubMed NCT01837251
  2. MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains dosing details in abstract PubMed NCT01802749

Carboplatin & Gemcitabine (GCb)

GCb: Gemcitabine & Carboplatin

Regimen variant #1, limited duration

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pfisterer et al. 2006 (AGO-OVAR 2.5) 1999-2002 Phase 3 (E-RT-esc) Carboplatin Superior PFS
Aghajanian et al. 2012 (OCEANS) 2007-2010 Phase 3 (C) Carboplatin, Gemcitabine, Bevacizumab Inferior PFS
Coleman et al. 2017 (NRG/GOG-0213) 2007-2011 Non-randomized part of phase 3 RCT

Chemotherapy

21-day cycle for 6 to 10 cycles


Regimen variant #2, indefinite

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sehouli et al. 2016 (HECTOR) 2007-2009 Randomized Phase 2 (C) Carboplatin & Topotecan Did not meet primary endpoint of PFS12
Pignata et al. 2021 (MITO 16) 2013-2016 Phase 3 (C) 1a. Carboplatin, PLD, Bevacizumab
1b. Carboplatin, Gemcitabine, Bevacizumab
1c. CP & Bevacizumab 		Inferior PFS
Liu et al. 2022 (NRG-GY004) 2016-02-04 to 2017-11-13 Phase 3 (C) 1. Olaparib
2. Cediranib & Olaparib 		Did not meet primary endpoint of PFS

Chemotherapy

21-day cycles

References

  1. AGO-OVAR 2.5: Pfisterer J, Plante M, Vergote I, du Bois A, Hirte H, Lacave AJ, Wagner U, Stähle A, Stuart G, Kimmig R, Olbricht S, Le T, Emerich J, Kuhn W, Bentley J, Jackisch C, Lück HJ, Rochon J, Zimmermann AH, Eisenhauer E; AGO-OVAR; NCIC-CTG; EORTC GCG. 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 Oct 10;24(29):4699-707. Epub 2006 Sep 11. link to original article contains dosing details in manuscript PubMed NCT00102414
  2. OCEANS: Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. 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 Jun 10;30(17):2039-45. Epub 2012 Apr 23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00434642
    1. Update: 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 Oct;139(1):10-6. Epub 2015 Aug 10. link to original article link to PMC article PubMed
  3. HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article contains dosing details in manuscript PubMed NCT00437307
  4. NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. 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 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article contains dosing details in abstract link to PMC article PubMed NCT00565851
    1. Update: Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, Kim JW, Park SY, Kim BG, Nam JH, Fujiwara K, Walker JL, Casey AC, Alvarez Secord A, Rubin S, Chan JK, DiSilvestro P, Davidson SA, Cohn DE, Tewari KS, Basen-Engquist K, Huang HQ, Brady MF, Mannel RS. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019 Nov 14;381(20):1929-1939. link to original article contains dosing details in manuscript link to PMC article PubMed
  5. MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains dosing details in abstract PubMed NCT01802749
  6. NRG-GY004: Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. link to original article contains dosing details in supplement link to PMC article PubMed NCT02446600

Carboplatin & Gemcitabine (GCb) & Bevacizumab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Aghajanian et al. 2012 (OCEANS)
ESMO-MCBS (3)
2007-2010 Phase 3 (E-RT-esc) GCb Superior PFS (primary endpoint)
Median PFS: 12.4 vs 8.4 mo
(HR 0.48, 95% CI 0.39-0.61)

Did not meet secondary endpoint of OS1
Median OS: 33.6 vs 32.9 mo
(HR 0.95, 95% CI 0.77-1.18)
Coleman et al. 2017 (NRG/GOG-0213) 2007-2011 Non-randomized part of phase 3 RCT
Pfisterer et al. 2020 (AGO-OVAR 2.21/ENGOT-ov 18) 2013-2015 Phase 3 (C) Carboplatin, Doxil, Bevaciuzmab Seems to have inferior PFS
Pignata et al. 2021 (MITO 16) 2013-2016 Phase 3 (E-esc) 1a. Carboplatin & PLD
1b. Carboplatin & Gemcitabine
1c. CP 		Superior PFS
Median PFS: 11.8 vs 8.8 mo
(HR 0.51, 95% CI 0.41-0.65)

1Reported efficacy for OS in OCEANS is based on the 2015 update.

Chemotherapy

Targeted therapy

21-day cycle for 6 to 10 cycles, based on response and protocol

Subsequent treatment

References

  1. OCEANS: Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. 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 Jun 10;30(17):2039-45. Epub 2012 Apr 23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00434642
    1. Update: 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 Oct;139(1):10-6. Epub 2015 Aug 10. link to original article link to PMC article PubMed
  2. NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. 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 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article contains dosing details in abstract link to PMC article PubMed NCT00565851
    1. Update: Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, Kim JW, Park SY, Kim BG, Nam JH, Fujiwara K, Walker JL, Casey AC, Alvarez Secord A, Rubin S, Chan JK, DiSilvestro P, Davidson SA, Cohn DE, Tewari KS, Basen-Engquist K, Huang HQ, Brady MF, Mannel RS. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019 Nov 14;381(20):1929-1939. link to original article contains dosing details in manuscript link to PMC article PubMed
  3. AGO-OVAR 2.21/ENGOT-ov 18: Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. Epub 2020 Apr 16. link to original article contains dosing details in abstract PubMed NCT01837251
  4. MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains dosing details in abstract PubMed NCT01802749

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin

Regimen variant #1, AUC 5/175, limited duration

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Coleman et al. 2017 (NRG/GOG-0213) 2007-2011 Phase 3 (C) Carboplatin, Paclitaxel, Bevacizumab Might have inferior OS
Vergote et al. 2019 (OAS 07OVA) 2009-2013 Phase 3 (C) Carboplatin & Paclitaxel micellar Non-inferior PFS
Pignata et al. 2017 (MITO-8) 2009-2015 Phase 3 (C) Investigator's choice1 of:
1a. PLD
1b. Topotecan
1c. Gemcitabine 		Did not meet primary endpoint of OS
Vergote et al. 2016 (FAR-131) 2009-NR Phase 3 (C) 1a. CP & Farletuzumab; 1.25 mg/kg
1b. DCb & Farletuzumab; 1.25 mg/kg
2a. CP & Farletuzumab; 2.5 mg/kg
2b. DCb & Farletuzumab; 2.5 mg/kg 		Did not meet primary endpoint of PFS
Shi et al. 2021 (SOC-1) 2012-2019 Non-randomized part of phase 3 RCT

1Initially PLD was the only option. After an amendment in 2012, topotecan, gemcitabine, or "any other drug approved in this setting" were allowed.

Preceding treatment

Chemotherapy

Supportive therapy

21-day cycle for 6 to 9 cycles

Subsequent treatment

  • MITO-8, upon progression: Non-platinum-based chemotherapy (NPBC)


Regimen variant #2, AUC 5/175, indefinite

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Parmar et al. 2003 (ICON4) 1996-2002 Phase 3 (E-esc) 1a. Carboplatin
1b. Cisplatin 		Seems to have superior OS
Median OS: 29 vs 24 mo
(HR 0.82, 95% CI 0.69-0.97)
Pujade-Lauraine et al. 2010 (CALYPSO) 2005-2007 Phase 3 (C) Carboplatin & PLD Inferior PFS
Sehouli et al. 2016 (HECTOR) 2007-2009 Randomized Phase 2 (C) Carboplatin & Topotecan Did not meet primary endpoint of PFS12
Coleman et al. 2017 (NRG/GOG-0213) 2007-2011 Phase 3 (C) TC & Bevacizumab Might have inferior OS
Oza et al. 2014 (D0810C00041) 2010 Randomized Phase 2 (C) CP & Olaparib Inferior PFS
Pignata et al. 2021 (MITO 16) 2013-2016 Phase 3 (C) 1a. Carboplatin, PLD, Bevacizumab
1b. Carboplatin, Gemcitabine, Bevacizumab
1c. CP & Bevacizumab 		Inferior PFS
Liu et al. 2022 (NRG-GY004) 2016-02-04 to 2017-11-13 Phase 3 (C) 1. Olaparib
2. Cediranib & Olaparib 		Did not meet primary endpoint of PFS

Chemotherapy

Supportive therapy

21-day cycles


Regimen variant #3, AUC 6/175, limited duration

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Vergote et al. 2019 (OAS 07OVA) 2009-2013 Phase 3 (C) Carboplatin & Paclitaxel micellar Non-inferior PFS
Vergote et al. 2016 (FAR-131) 2009-NR Phase 3 (C) 1a. CP & Farletuzumab; 1.25 mg/kg
1b. DCb & Farletuzumab; 1.25 mg/kg
2a. CP & Farletuzumab; 2.5 mg/kg
2b. DCb & Farletuzumab; 2.5 mg/kg 		Did not meet primary endpoint of PFS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #4, AUC 6/175, indefinite

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Oza et al. 2014 (D0810C00041) 2010 Randomized Phase 2 (C) CP & Olaparib Inferior PFS
Liu et al. 2022 (NRG-GY004) 2016-02-04 to 2017-11-13 Phase 3 (C) 1. Olaparib
2. Cediranib & Olaparib 		Did not meet primary endpoint of PFS

Chemotherapy

Supportive therapy

21-day cycles

References

  1. ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. 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 Jun 21;361(9375):2099-106. link to original article contains dosing details in manuscript PubMed NCT00002894
  2. CALYPSO: Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B, Vergote I, Pignata S, Ferrero A, Sehouli J, Lortholary A, Kristensen G, Jackisch C, Joly F, Brown C, Le Fur N, du Bois A. Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol. 2010 Jul 10;28(20):3323-9. Epub 2010 May 24. link to original article contains dosing details in manuscript PubMed NCT00189553
    1. Update: Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Pujade Lauraine E. 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 Aug 7;107(4):588-91. Epub 2012 Jul 26. link to original article contains dosing details in manuscript link to PMC article PubMed
  3. D0810C00041: Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Špaček 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 Jan;16(1):87-97. Epub 2014 Dec 4. Erratum in: Lancet Oncol. 2015 Feb;16(2):e55. Lancet Oncol. 2015 Jan;16(1):e6. link to original article contains dosing details in abstract PubMed NCT01081951
  4. FAR-131: Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, Weil SC, Bamias A, Fujiwara K, Ochiai K, Poole C, Gorbunova V, Wang W, O'Shannessy D, Herzog TJ. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol. 2016 Jul 1;34(19):2271-8. Epub 2016 Mar 21. link to original article PubMed NCT00849667
  5. HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article contains dosing details in manuscript PubMed NCT00437307
  6. NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. 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 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article contains dosing details in abstract link to PMC article PubMed NCT00565851
  7. MITO-8: Pignata S, Scambia G, Bologna A, Signoriello S, Vergote IB, Wagner U, Lorusso D, Murgia V, Sorio R, Ferrandina G, Sacco C, Cormio G, Breda E, Cinieri S, Natale D, Mangili G, Pisano C, Cecere SC, Di Napoli M, Salutari V, Raspagliesi F, Arenare L, Bergamini A, Bryce J, Daniele G, Piccirillo MC, Gallo C, Perrone F. 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 Oct 10;35(29):3347-3353. Epub 2017 Aug 21. link to original article contains dosing details in manuscript PubMed NCT00657878
  8. OAS 07OVA: Vergote I, Bergfeldt K, Franquet A, Lisyanskaya AS, Bjermo H, Heldring N, Buyse M, Brize A. A randomized phase III trial in patients with recurrent platinum sensitive ovarian cancer comparing efficacy and safety of paclitaxel micellar and Cremophor EL-paclitaxel. Gynecol Oncol. 2020 Feb;156(2):293-300. Epub 2019 Dec 9. link to original article contains dosing details in abstract PubMed NCT00989131
  9. MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains dosing details in abstract PubMed NCT01802749
  10. SOC-1: Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, Jia H, Huang X, Cai Y, Yin S, Jiang R, Tian W, Gao W, Liu J, Yang H, Cheng X, Zang R. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):439-449. Epub 2021 Mar 8. link to original article contains dosing details in abstract PubMed NCT01611766
  11. NRG-GY004: Liu JF, Brady MF, Matulonis UA, Miller A, Kohn EC, Swisher EM, Cella D, Tew WP, Cloven NG, Muller CY, Bender DP, Moore RG, Michelin DP, Waggoner SE, Geller MA, Fujiwara K, D'Andre SD, Carney M, Alvarez Secord A, Moxley KM, Bookman MA. Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2022 Jul 1;40(19):2138-2147. Epub 2022 Mar 15. link to original article contains dosing details in supplement link to PMC article PubMed NCT02446600

Carboplatin & Paclitaxel (CP) & Bevacizumab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Coleman et al. 2017 (NRG/GOG-0213) 2007-2011 Phase 3 (E-RT-esc) Carboplatin & Paclitaxel Might have superior OS
Median OS: 42.2 vs 37.3 mo
(HR 0.83, 95% CI 0.68-1.005)
Pignata et al. 2021 (MITO 16) 2013-2016 Phase 3 (E-esc) 1a. Carboplatin & PLD
1b. Carboplatin & Gemcitabine
1c. CP 		Superior PFS
Median PFS: 11.8 vs 8.8 mo
(HR 0.51, 95% CI 0.41-0.65)

Chemotherapy

  • Carboplatin (Paraplatin) as follows:
    • Cycles 1 to 6 up to 8: AUC 5 IV over 60 minutes once on day 1, given third
  • Paclitaxel (Taxol) as follows:
    • Cycles 1 to 6 up to 8: 175 mg/m2 IV over 3 hours once on day 1, given first

Targeted therapy

  • Bevacizumab (Avastin) 15 mg/kg IV over 90 minutes once on day 1, given second
    • If tolerated, infusion time is reduced to 60 minutes with cycle 2, and 30 minutes with cycle 3 onwards

21-day cycles

References

  1. NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. 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 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00565851
  2. MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains dosing details in abstract PubMed NCT01802749

Carboplatin & Paclitaxel (CP) & Olaparib

CP & Olaparib: Carboplatin, Paclitaxel, Olaparib

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Oza et al. 2014 (D0810C00041) 2010 Randomized Phase 2 (E-esc) Carboplatin & Paclitaxel Superior PFS
Median PFS: 12.2 vs 9.6 mo
(HR 0.51, 95% CI 0.34-0.77)

Chemotherapy

Targeted therapy

  • Olaparib (Lynparza) as follows:
    • Cycles 1 to 6: 200 mg PO twice per day on days 1 to 10
    • Cycle 7 onwards: 400 mg PO twice per day

21-day cycles

References

  1. D0810C00041: Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Špaček 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 Jan;16(1):87-97. Epub 2014 Dec 4. Erratum in: Lancet Oncol. 2015 Feb;16(2):e55. Lancet Oncol. 2015 Jan;16(1):e6. link to original article contains dosing details in manuscript PubMed NCT01081951

Cisplatin & Gemcitabine (GC)

Regimen

Study Dates of enrollment Evidence
Rose et al. 2003c NR Phase 2

Chemotherapy

Supportive therapy

21-day cycles

References

  1. Rose PG, Mossbruger K, Fusco N, Smrekar M, Eaton S, Rodriguez M. Gemcitabine reverses cisplatin resistance: demonstration of activity in platinum- and multidrug-resistant ovarian and peritoneal carcinoma. Gynecol Oncol. 2003 Jan;88(1):17-21. link to original article contains dosing details in manuscript PubMed

Cisplatin & Paclitaxel

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Parmar et al. 2003 (ICON4) 1996-2002 Phase 3 (E-esc) 1a. Carboplatin
1b. Cisplatin 		Seems to have superior OS
Median OS: 29 vs 24 mo
(HR 0.82, 95% CI 0.69-0.97)

Chemotherapy

21-day cycles

References

  1. ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. 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 Jun 21;361(9375):2099-106. link to original article contains dosing details in manuscript PubMed NCT00002894

Etoposide monotherapy

Regimen

Study Dates of enrollment Evidence Efficacy
Rose et al. 1998 1992-1995 Phase 2 ORR: 34%

Chemotherapy

  • Etoposide (Vepesid) 50 mg/m2 PO once per day on days 1 to 21
    • Dosage for patients with previous pelvic radiation: 30 mg/m2 PO once per day on days 1 to 21; dose could be increased up to 50 mg/m2 depending on toxicity

28-day cycles

References

  1. Rose PG, Blessing JA, Mayer AR, Homesley HD; Gynecologic Oncology Group. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. link to original article contains dosing details in manuscript PubMed

nab-Paclitaxel monotherapy

Regimen

Study Dates of enrollment Evidence
Teneriello et al. 2009 2005-2006 Phase 2

Chemotherapy

21-day cycle for 6 to 8 cycles

References

  1. Teneriello MG, Tseng PC, Crozier M, Encarnacion C, Hancock K, Messing MJ, Boehm KA, Williams A, Asmar L. Phase II evaluation of nanoparticle albumin-bound paclitaxel in platinum-sensitive patients with recurrent ovarian, peritoneal, or fallopian tube cancer. J Clin Oncol. 2009 Mar 20;27(9):1426-31. Epub 2009 Feb 17. link to original article contains dosing details in manuscript PubMed

Rucaparib monotherapy

Regimen

Study Dates of enrollment Evidence
Swisher et al. 2016 (ARIEL2)
ESMO-MCBS (3)
2013-10-30 to 2014-12-19 Phase 2 (RT)

Note: the MCBS score is for the BRCA-mutated subgroup, only.

Targeted therapy

28-day cycles

References

  1. ARIEL2: 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 Jan;18(1):75-87. Epub 2016 Nov 28. link to original article contains dosing details in manuscript PubMed NCT01891344
    1. Pooled subgroup analysis: Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmaña J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. link to original article PubMed

Maintenance after second-line therapy for platinum-sensitive disease

Niraparib monotherapy

AIM pathway regimen 2022-08-01

Regimen variant #1, 200 mg/day

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Wu et al. 2021 (NORA) 2017-2019 Phase 3 (E-esc) Placebo Superior PFS
Median PFS: 18.3 vs 5.4 mo
(HR 0.32, 95% CI 0.23-0.45)

Note: after a mid-protocol amendment, this was the dosing for patients with bodyweight of less than 77 kg, or a platelet count of less than 150 × 109/L.

Preceding treatment

Targeted therapy

Continued indefinitely


Regimen variant #2, 300 mg/day

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Mirza et al. 2016 (NOVA)
ESMO-MCBS (3)
2013-NR Phase 3 (E-RT-esc) Placebo Superior PFS1
Median PFS: 9.3 vs 3.9 mo
(HR 0.45, 95% CI 0.34-0.61)
Wu et al. 2021 (NORA) 2017-2019 Phase 3 (E-esc) Placebo Superior PFS
Median PFS: 18.3 vs 5.4 mo
(HR 0.32, 95% CI 0.23-0.45)

1Reported efficacy is for the overall non-gBRCAm cohort.
Note: in NORA, after a mid-protocol amendment, this was the dosing for patients with bodyweight of 77 kg or more, and a platelet count of 150 × 109/L or more.

Preceding treatment

Targeted therapy

Continued indefinitely

References

  1. 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 contains dosing details in manuscript PubMed NCT01847274
    1. 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 PubMed
    2. 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 PubMed
    3. 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 PubMed
  2. 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 contains dosing details in abstract PubMed NCT03705156

Olaparib monotherapy

AIM pathway regimen 2022-08-01

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ledermann et al. 2012 (Study 19)
ESMO-MCBS (2)
2008-2010 Randomized Phase 2 (E-RT-esc) Placebo Might have superior OS1
Median OS: 29.8 vs 27.8 mo
(HR 0.73, 95% CI 0.55-0.95)

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."

Targeted therapy

Continued indefinitely

References

  1. 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. link to original article contains dosing details in manuscript PubMed NCT00753545
    1. 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 PubMed
    2. 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 PubMed
    3. 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 PubMed
  2. ICON9: NCT03278717

Rucaparib monotherapy

AIM pathway regimen 2022-08-01

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Coleman et al. 2017 (ARIEL3)
ESMO-MCBS (3)
2014-2016 Phase 3 (E-RT-esc) Placebo Superior PFS (primary endpoint)
Median PFS: 16.6 vs 5.4 mo
(HR 0.23, 95% CI 0.16-0.34)

Preceding treatment

Targeted therapy

28-day cycles

References

  1. 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 contains dosing details in manuscript link to PMC article PubMed NCT01968213
    1. 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 PubMed
    2. 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 PubMed

Relapsed or recurrent disease, platinum-resistant

Altretamine monotherapy

Regimen

Study Dates of enrollment Evidence
Markman et al. 1998 NR Phase 2 (RT)

Note: there is not enough information in the FDA label to determine for sure whether this is one of the registration trials; it is representative of many phase 2 trials of this agent.

Chemotherapy

28-day cycles

References

  1. Markman M, Blessing JA, Moore D, Ball H, Lentz SS; Gynecologic Oncology Group. Altretamine (hexamethylmelamine) in platinum-resistant and platinum-refractory ovarian cancer: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 1998 Jun;69(3):226-9. link to original article PubMed

Bevacizumab monotherapy

AIM pathway regimen 2022-08-01

Regimen

Study Dates of enrollment Evidence
Burger et al. 2007 2002-2004 Phase 2
Cannistra et al. 2007 2005 Phase 2

Targeted therapy

21-day cycles

References

  1. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI; Gynecologic Oncology Group. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Nov 20;25(33):5165-71. Erratum in: J Clin Oncol. 2014 Nov 10;32(32):3686. link to original article contains dosing details in manuscript PubMed
  2. Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, Douglas J, Burger RA, Armstrong D, Wenham R, McGuire W. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007 Nov 20;25(33):5180-6. Erratum in: J Clin Oncol. 2008 Apr 1;26(10):1773. link to original article contains dosing details in manuscript PubMed

Docetaxel monotherapy

AIM pathway regimen 2022-08-01

Regimen

Study Dates of enrollment Evidence
Rose et al. 2003a 1998-06 to 2000-01 Phase 2

Chemotherapy

Supportive therapy

21-day cycles

References

  1. Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, Moore DH; Gynecologic Oncology Group. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Feb;88(2):130-5. link to original article contains dosing details in manuscript PubMed

Etoposide monotherapy

Regimen

Study Dates of enrollment Evidence Efficacy
Rose et al. 1998 1992-1995 Phase 2 ORR: 27%

Chemotherapy

  • Etoposide (Vepesid) 50 mg/m2 PO once per day on days 1 to 21
    • Dosage for patients with previous pelvic radiation: 30 mg/m2 PO once per day on days 1 to 21; dose could be increased up to 50 mg/m2 depending on toxicity

28-day cycles

References

  1. Rose PG, Blessing JA, Mayer AR, Homesley HD; Gynecologic Oncology Group. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. link to original article contains dosing details in manuscript PubMed

Gemcitabine monotherapy

Regimen variant #1, 2 weeks out of 3

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Mutch et al. 2007 (B9E-US-S301) 2002-2004 Phase 3 (E-switch-ic) PLD Did not meet primary endpoint of PFS
Kurzeder et al. 2016 (PENELOPE) 2013-2014 Phase 3 (C) 1a. Gemcitabine & Pertuzumab
1b. Paclitaxel & Pertuzumab
1c. Topotecan & Pertuzumab 		Did not meet primary endpoint of PFS

Chemotherapy

21-day cycles


Regimen variant #2, 3 weeks out of 4

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ferrandina et al. 2008 (MITO-3) 2003-2007 Phase 3 (E-switch-ic) PLD Might have superior ORR
Lheureux et al. 2021 (PHL-093) 2014-2018 Phase 3 (C) Adavosertib & Gemcitabine Inferior PFS
Hamanishi et al. 2021 (NINJA) 2015-10-07 to 2017-12-21 Phase 3 (C) Nivolumab Did not meet primary endpoint of OS
Awaiting publication (NItCHE) 2020-ongoing Phase 3 (C) Niraparib & Dostarlimab TBD

Chemotherapy

28-day cycles

References

  1. B9E-US-S301: Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. link to original article contains dosing details in manuscript PubMed NCT00191607
  2. MITO-3: Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. link to original article contains dosing details in manuscript PubMed
  3. PENELOPE: Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. link to original article contains dosing details in manuscript PubMed NCT01684878
    1. Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
  4. PHL-093: Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, Olawaiye AB, Ellard SL, Weberpals JI, Wahner Hendrickson AE, Fleming GF, Welch S, Dhani NC, Stockley T, Rath P, Karakasis K, Jones GN, Jenkins S, Rodriguez-Canales J, Tracy M, Tan Q, Bowering V, Udagani S, Wang L, Kunos CA, Chen E, Pugh TJ, Oza AM. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021 Jan 23;397(10271):281-292. link to original article contains dosing details in abstract PubMed NCT02151292
  5. NINJA: Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, Matsumoto K, Ito K, Mandai M, Nakai H, Sakuragi N, Watari H, Takahashi N, Kato H, Hasegawa K, Yonemori K, Mizuno M, Takehara K, Niikura H, Sawasaki T, Nakao S, Saito T, Enomoto T, Nagase S, Suzuki N, Matsumoto T, Kondo E, Sonoda K, Aihara S, Aoki Y, Okamoto A, Takano H, Kobayashi H, Kato H, Terai Y, Takazawa A, Takahashi Y, Namba Y, Aoki D, Fujiwara K, Sugiyama T, Konishi I. Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol. 2021 Nov 20;39(33):3671-3681. Epub 2021 Sep 2. link to original article contains dosing details in manuscript link to PMC article PubMed JapicCTI-153004
  6. NItCHE: NCT04679064

Gemcitabine & Pegylated liposomal doxorubicin

Regimen

Study Dates of enrollment Evidence
Ferrandina et al. 2005 2000-12 to 2004-01 Phase 2

Chemotherapy

Supportive therapy

21-day cycles

References

  1. Ferrandina G, Paris I, Ludovisi M, D'Agostino G, Testa A, Lorusso D, Zanghi M, Pisconti S, Pezzella G, Adamo V, Breda E, Scambia G. Gemcitabine and liposomal doxorubicin in the salvage treatment of ovarian cancer: updated results and long-term survival. Gynecol Oncol. 2005 Aug;98(2):267-73. link to original article contains dosing details in manuscript PubMed

Mirvetuximab soravtansine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Moore et al. 2021 (FORWARD I) 2017-2018 Phase 3 (E-switch-ooc) Physician's choice of:
1a. Paclitaxel
1b. Pegylated liposomal doxorubicin
1c. Topotecan 		Did not meet primary endpoint of PFS
Median PFS: 4.1 vs 4.4 mo
(HR 0.98, 95% CI 0.73-1.31)
Awaiting publication (SORAYA) 2020-2021 Non-randomized (RT)

Biomarker eligibility criteria

  • High folate receptor-alpha expression

Antibody-drug conjugate therapy

21-day cycles

References

  1. FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article contains dosing details in manuscript PubMed NCT02631876
  2. SORAYA: NCT04296890

Paclitaxel monotherapy

Regimen variant #1, 80 mg/m2 3 out of 4 weeks

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Moore et al. 2021 (FORWARD I) 2017-2018 Phase 3 (C) Mirvetuximab soravtansine Did not meet primary endpoint of PFS
Awaiting publication (NItCHE) 2020-ongoing Phase 3 (C) Niraparib & Dostarlimab TBD

Biomarker eligibility criteria

  • FORWARD I: High folate receptor-alpha expression

Chemotherapy

28-day cycles


Regimen variant #2, 80 mg/m2 weekly

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Markman et al. 2006 NR Phase 2
Lindemann et al. 2017 (Ovaresist) 2002-2007 Phase 3 (C) Tamoxifen Superior PFS
Pujade-Lauraine et al. 2014 (AURELIA) 2009-2011 Phase 3 (C) 1a. Paclitaxel & Bevacizumab
1b. PLD & Bevacizumab
1c. Topotecan & Bevacizumab 		Inferior PFS
Monk et al. 2014 (TRINOVA-1) 2010-2012 Phase 3 (C) Paclitaxel & Trebananib Inferior PFS
Pignata et al. 2015 (MITO 11) 2010-2013 Randomized Phase 2 (C) Paclitaxel & Pazopanib Inferior PFS
Kurzeder et al. 2016 (PENELOPE) 2013-2014 Phase 3 (C) 1a. Gemcitabine & Pertuzumab
1b. Paclitaxel & Pertuzumab
1c. Topotecan & Pertuzumab 		Did not meet primary endpoint of PFS

Note: PENELOPE reports giving paclitaxel on days 1, 8, 15 of a 21-day cycle, which is identical to the schedule below. Ovaresist met its primary endpoint of superior HrQOL for the experimental (tamoxifen) arm but had inferior PFS (secondary endpoint) for the experimental arm, and this is the efficacy reported here.

Chemotherapy

Supportive therapy

  • Dexamethasone (Decadron) 10 mg IV or PO once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to paclitaxel
  • Diphenhydramine (Benadryl) 25 to 50 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to paclitaxel
  • H2 blocker once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to paclitaxel

28-day cycles


Regimen variant #3, 175 mg/m2, q3wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Eisenhauer et al. 1994 1991-1992 Phase 3 (E-RT-switch-ic) Paclitaxel; 135 mg/m2 Seems to have superior PFS
Gore et al. 1995 1992-1993 Non-randomized
ten Bokkel Huinink et al. 1997 NR Phase 3 (E-switch-ic) Topotecan Might have inferior TTP1
Cantù et al. 1999 1992-1995 Phase 3 (E-de-esc) CAP Seems to have inferior OS
Omura et al. 2003 1992-1995 Phase 3 (C) Paclitaxel; 250 mg/m2 Seems to have inferior ORR
Buda et al. 2004 1994-1999 Phase 3 (C) Epirubicin & Paclitaxel Did not meet primary endpoint of OS

1Reported efficacy for ten Bokkel Huinink et al. 1997 is based on the 2004 update.

Chemotherapy

  • Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
    • Omura et al. 2003 gave over 24 hours

21-day cycles


Regimen variant #4, 200 mg/m2, q3wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Rosenberg et al. 2002 1995-1998 Phase 3 (C) Paclitaxel; weekly 67 mg/m2 Did not meet primary endpoint of ORR

Chemotherapy

21-day cycles


Regimen variant #5, with range

Study Dates of enrollment Evidence
McGuire et al. 1989 NR Phase 2
Kohn et al. 1994 1991-01-01 to 1992-04-01 Phase 2

Note: this variant is of historic interest.

Chemotherapy

References

  1. McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DK, Donehower RC. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med. 1989 Aug 15;111(4):273-9. link to original article PubMed
  2. Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, Gianni L, Myles J, van der Burg ME, Kerr I, Vermorken JB, Buser K, Colombo N, Bacon M, Santabarbara P, Onetto N, Winograd B, Canetta R. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol. 1994 Dec;12(12):2654-66. link to original article contains dosing details in abstract PubMed
  3. Kohn EC, Sarosy G, Bicher A, Link C, Christian M, Steinberg SM, Rothenberg M, Adamo DO, Davis P, Ognibene FP, Cunnion RE, Reed E. Dose-intense taxol: high response rate in patients with platinum-resistant recurrent ovarian cancer. J Natl Cancer Inst. 1994 Jan 5;86(1):18-24. link to original article PubMed
  4. Gore ME, Levy V, Rustin G, Perren T, Calvert AH, Earl H, Thompson JM. Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer. 1995 Oct;72(4):1016-9. link to original article link to PMC article PubMed
  5. ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I, Broom C, Scarabelli C, Davidson N, Spanczynski M, Bolis G, Malmström H, Coleman R, Fields SC, Heron JF. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997 Jun;15(6):2183-93. link to original article contains dosing details in abstract PubMed
    1. Update: ten Bokkel Huinink W, Lane SR, Ross GA; International Topotecan Study Group. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Ann Oncol. 2004 Jan;15(1):100-3. link to original article PubMed
  6. Cantù MG, Buda A, Parma G, Rossi R, Floriani I, Bonazzi C, Dell'Anna T, Torri V, Colombo N. Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens. J Clin Oncol. 2002 Mar 1;20(5):1232-7. link to original article PubMed
  7. Rosenberg P, Andersson H, Boman K, Ridderheim M, Sorbe B, Puistola U, Parö G. Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum. Acta Oncol. 2002;41(5):418-24. link to original article PubMed
  8. Omura GA, Brady MF, Look KY, Averette HE, Delmore JE, Long HJ, Wadler S, Spiegel G, Arbuck SG. Phase III trial of paclitaxel at two dose levels, the higher dose accompanied by filgrastim at two dose levels in platinum-pretreated epithelial ovarian cancer: an intergroup study. J Clin Oncol. 2003 Aug 1;21(15):2843-8. Epub 2003 Jun 13. link to original article contains dosing details in abstract PubMed
  9. Buda A, Floriani I, Rossi R, Colombo N, Torri V, Conte PF, Fossati R, Ravaioli A, Mangioni C; GONO. Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, GONO (Gruppo Oncologico Nord Ovest) group and IOR (Istituto Oncologico Romagnolo) group. Br J Cancer. 2004 Jun 1;90(11):2112-7. link to original article link to PMC article contains dosing details in manuscript PubMed
  10. Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, Waggoner S; Gynecologic Oncology Group. 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 Jun;101(3):436-40. Epub 2005 Dec 2. link to original article contains dosing details in manuscript PubMed
  11. AURELIA: 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 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains dosing details in manuscript PubMed NCT00976911
    1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. 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 May 1;32(13):1309-16. link to original article link to PMC article PubMed
    2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
  12. TRINOVA-1: Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón 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 Jul;15(8):799-808. Epub 2014 Jun 17. link to original article PubMed NCT01204749
    1. Update: Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón DG, Coleman RL, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Ma H, Vogl FD, Bach BA, Oza AM. Final results of a phase 3 study of trebananib plus weekly paclitaxel in recurrent ovarian cancer (TRINOVA-1): Long-term survival, impact of ascites, and progression-free survival-2. Gynecol Oncol. 2016 Oct;143(1):27-34. Epub 2016 Aug 18. link to original article PubMed
  13. MITO 11: 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; MITO. 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 May;16(5):561-8. Epub 2015 Apr 14. link to original article contains dosing details in abstract PubMed NCT01644825
  14. PENELOPE: Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. link to original article contains dosing details in manuscript PubMed NCT01684878
    1. Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
  15. Ovaresist: Lindemann K, Gibbs E, Åvall-Lundqvist E, dePont Christensen R, Woie K, Kalling M, Auranen A, Grenman S, Hoegberg T, Rosenberg P, Skeie-Jensen T, Hjerpe E, Dørum A, Gebski V, Kristensen G. Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). Br J Cancer. 2017 Feb 14;116(4):455-463. Epub 2017 Jan 24. link to original article contains dosing details in abstract link to PMC article PubMed NCT02728622
  16. FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article contains dosing details in manuscript PubMed NCT02631876
  17. AGO-OVAR 2.29: NCT03353831
  18. EPIK-O: NCT04729387
  19. GOG-3059: NCT04729608
  20. NItCHE: NCT04679064
  21. OVAL: NCT03398655

Paclitaxel & Bevacizumab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)
ESMO-MCBS (4)
2009-2011 Phase 3 (E-RT-esc) 1a. Paclitaxel
1b. PLD
1c. Topotecan 		Superior PFS
Median PFS: 6.7 vs 3.4 mo
(HR 0.48, 95% CI 0.38-0.60)

Chemotherapy

Targeted therapy

28-day cycles

References

  1. AURELIA: 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 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains dosing details in manuscript PubMed NCT00976911
    1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. 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 May 1;32(13):1309-16. link to original article link to PMC article PubMed
    2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
  2. NItCHE: NCT04679064

Paclitaxel & Pazopanib

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pignata et al. 2015 (MITO 11) 2010-2013 Randomized Phase 2 (E-esc) Paclitaxel Superior PFS

Chemotherapy

Targeted therapy

21-day cycles

References

  1. MITO 11: 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; MITO. 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 May;16(5):561-8. Epub 2015 Apr 14. link to original article contains dosing details in abstract PubMed NCT01644825

Pazopanib monotherapy

Regimen

Study Dates of enrollment Evidence
Friedlander et al. 2010 NR Phase 2

Targeted therapy

Continued indefinitely

References

  1. Friedlander M, Hancock KC, Rischin D, Messing MJ, Stringer CA, Matthys GM, Ma B, Hodge JP, Lager JJ. A Phase II, open-label study evaluating pazopanib in patients with recurrent ovarian cancer. Gynecol Oncol. 2010 Oct;119(1):32-7. Epub 2010 Jun 27. link to original article contains dosing details in manuscript PubMed

Pegylated liposomal doxorubicin monotherapy

Regimen variant #1, 40 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Lindemann et al. 2017 (Ovaresist) 2002-2007 Phase 3 (C) Tamoxifen Superior PFS
Ferrandina et al. 2008 (MITO-3) 2003-2007 Phase 3 (E-switch-ic) Gemcitabine Might have inferior ORR
Pujade-Lauraine et al. 2014 (AURELIA) 2009-2011 Phase 3 (C) 1a. Paclitaxel & Bevacizumab
1b. PLD & Bevacizumab
1c. Topotecan & Bevacizumab 		Inferior PFS
Motohashi et al. 2020 (JGOG 3018) 2010-2017 Phase 3 (E-de-esc) PLD; 50 mg/m2 Inconclusive whether non-inferior PFS
Pujade-Lauraine et al. 2021 (JAVELIN Ovarian 200) 2016-2017 Phase 3 (C) 1. Avelumab
2. PLD & Avelumab 		Did not meet primary endpoints of PFS/OS
Moore et al. 2021 (FORWARD I) 2017-2018 Phase 3 (C) Mirvetuximab soravtansine Did not meet primary endpoint of PFS
Awaiting publication (NItCHE) 2020-ongoing Phase 3 (C) Niraparib & Dostarlimab TBD

Note: Ovaresist met its primary endpoint of superior HrQOL for the experimental (tamoxifen) arm but had inferior PFS (secondary endpoint) for the experimental arm, and this is the efficacy reported here.

Biomarker eligibility criteria

  • FORWARD I: High folate receptor-alpha expression

Chemotherapy

Supportive therapy

28-day cycles


Regimen variant #2, 50 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Muggia et al. 1997 1994-1995 Phase 2 (RT)
Gordon et al. 2000 NR-1998 Phase 2 (RT)
Gordon et al. 2001 (Doxil Study 30-49) 1997-1999 Phase 3 (E-RT-switch-ic) Topotecan Might have superior PFS
Mutch et al. 2007 (B9E-US-S301) 2002-2004 Phase 3 (C) Gemcitabine Did not meet primary endpoint of PFS
Vergote et al. 2009 (ASSIST-1) 2003-2006 Phase 3 (C) Canfosfamide Superior OS
Monk et al. 2010 (OVA-301) 2005-2007 Phase 3 (C) PLD & Trabectedin Might have inferior OS1
Colombo et al. 2012 (CEPO906A2303) 2005-2009 Phase 3 (C) Patupilone Did not meet primary endpoint of OS
Vergote et al. 2010 (ASSIST-5) 2006-2007 Phase 3 (C) Canfosfamide & PLD Did not meet primary endpoint of PFS
Motohashi et al. 2020 (JGOG 3018) 2010-2017 Phase 3 (C) PLD; 40 mg/m2 Inconclusive whether non-inferior PFS
Marth et al. 2016 (TRINOVA-2) 2011-2013 Phase 3 (C) PLD & Trebananib Did not meet primary endpoint of PFS
Monk et al. 2020 (CR100983) 2013-2018 Phase 3 (C) PLD & Trabectedin Did not meet primary endpoint of OS
Gaillard et al. 2021 (CORAIL) 2015-06-26 to 2018-10-12 Phase 3 (C) Lurbinectedin Did not meet primary endpoint of PFS
Hamanishi et al. 2021 (NINJA) 2015-10-07 to 2017-12-21 Phase 3 (C) Nivolumab Did not meet primary endpoint of OS

1Reported efficacy for OVA-301 is based on the 2012 update.

Chemotherapy

28-day cycles

References

  1. Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, Roman L, Uziely B, Muderspach L, Garcia A, Burnett A, Greco FA, Morrow CP, Paradiso LJ, Liang LJ. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol. 1997 Mar;15(3):987-93. link to original article PubMed
  2. Gordon AN, Granai CO, Rose PG, Hainsworth J, Lopez A, Weissman C, Rosales R, Sharpington T. Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3093-100. link to original article contains dosing details in abstract PubMed
  3. Doxil Study 30-49: Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001 Jul 15;19(14):3312-22. link to original article PubMed
    1. Update: Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1-8. link to original article contains dosing details in manuscript PubMed
  4. B9E-US-S301: Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org NCT00191607
  5. MITO-3: Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, Del Medico P, Scaltriti L, Katsaros D, Priolo D, Scambia G. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008 Feb 20;26(6):890-6. link to original article contains dosing details in manuscript PubMed
  6. ASSIST-1: Vergote I, Finkler N, del Campo J, Lohr A, Hunter J, Matei D, Kavanagh J, Vermorken JB, Meng L, Jones M, Brown G, Kaye S; ASSIST-1 Study Group. Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or -resistant ovarian cancer. Eur J Cancer. 2009 Sep;45(13):2324-32. Epub 2009 Jun 8. link to original article contains dosing details in abstract PubMed NCT00057720
  7. ASSIST-5: Vergote I, Finkler NJ, Hall JB, Melnyk O, Edwards RP, Jones M, Keck JG, Meng L, Brown GL, Rankin EM, Burke JJ, Boccia RV, Runowicz CD, Rose PG. Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2010 Jul;20(5):772-80. link to original article PubMed NCT00350948
  8. OVA-301: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010 Jul 1;28(19):3107-14. Epub 2010 Jun 1. link to original article contains dosing details in abstract PubMed NCT00113607
    1. PRO analysis: Krasner CN, Poveda A, Herzog TJ, Vermorken JB, Kaye SB, Nieto A, Claret PL, Park YC, Parekh T, Monk BJ. Patient-reported outcomes in relapsed ovarian cancer: results from a randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone. Gynecol Oncol. 2012 Oct;127(1):161-7. Epub 2012 Jul 2. link to original article PubMed
    2. Update: 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 Oct;48(15):2361-8. Epub 2012 Apr 26. link to original article PubMed
  9. CEPO906A2303: Colombo N, Kutarska E, Dimopoulos M, Bae DS, Rzepka-Gorska I, Bidzinski M, Scambia G, Engelholm SA, Joly F, Weber D, El-Hashimy M, Li J, Souami F, Wing P, Engelholm S, Bamias A, Schwartz P. Randomized, open-label, phase III study comparing patupilone (EPO906) with pegylated liposomal doxorubicin in platinum-refractory or -resistant patients with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. J Clin Oncol. 2012 Nov 1;30(31):3841-7. Epub 2012 Sep 17. link to original article contains dosing details in abstract PubMed NCT00262990
  10. AURELIA: 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 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains dosing details in manuscript PubMed NCT00976911
    1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. 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 May 1;32(13):1309-16. link to original article link to PMC article PubMed
    2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
  11. TRINOVA-2: Marth C, Vergote I, Scambia G, Oberaigner W, Clamp A, Berger R, Kurzeder C, Colombo N, Vuylsteke P, Lorusso D, Hall M, Renard V, Pignata S, Kristeleit R, Altintas S, Rustin G, Wenham RM, Mirza MR, Fong PC, Oza A, Monk BJ, Ma H, Vogl FD, Bach BA. ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer. Eur J Cancer. 2017 Jan;70:111-121. Epub 2016 Dec 1. link to original article contains dosing details in abstract PubMed NCT01281254
  12. Ovaresist: Lindemann K, Gibbs E, Åvall-Lundqvist E, dePont Christensen R, Woie K, Kalling M, Auranen A, Grenman S, Hoegberg T, Rosenberg P, Skeie-Jensen T, Hjerpe E, Dørum A, Gebski V, Kristensen G. Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist). Br J Cancer. 2017 Feb 14;116(4):455-463. Epub 2017 Jan 24. link to original article contains dosing details in abstract link to PMC article PubMed NCT02728622
  13. CR100983: Monk BJ, Herzog TJ, Wang G, Triantos S, Maul S, Knoblauch R, McGowan T, Shalaby WSW, Coleman RL. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol. 2020 Mar;156(3):535-544. Epub 2020 Jan 8. link to original article contains dosing details in abstract PubMed NCT01846611
  14. JGOG 3018: Motohashi T, Yabuno A, Michimae H, Ohishi T, Nonaka M, Takano M, Nishio S, Fujiwara H, Fujiwara K, Kondo E, Sugiyama T, Tabata T. Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial. J Gynecol Oncol. 2021 Jan;32(1):e9. Epub 2020 Nov 10. link to original article contains dosing details in abstract link to PMC article PubMed UMIN000003130
  15. FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article contains dosing details in manuscript PubMed NCT02631876
  16. JAVELIN Ovarian 200: Pujade-Lauraine E, Fujiwara K, Ledermann JA, Oza AM, Kristeleit R, Ray-Coquard IL, Richardson GE, Sessa C, Yonemori K, Banerjee S, Leary A, Tinker AV, Jung KH, Madry R, Park SY, Anderson CK, Zohren F, Stewart RA, Wei C, Dychter SS, Monk BJ. Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol. 2021 Jul;22(7):1034-1046. Epub 2021 Jun 15. link to original article contains dosing details in abstract PubMed NCT02580058
  17. NINJA: Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, Matsumoto K, Ito K, Mandai M, Nakai H, Sakuragi N, Watari H, Takahashi N, Kato H, Hasegawa K, Yonemori K, Mizuno M, Takehara K, Niikura H, Sawasaki T, Nakao S, Saito T, Enomoto T, Nagase S, Suzuki N, Matsumoto T, Kondo E, Sonoda K, Aihara S, Aoki Y, Okamoto A, Takano H, Kobayashi H, Kato H, Terai Y, Takazawa A, Takahashi Y, Namba Y, Aoki D, Fujiwara K, Sugiyama T, Konishi I. Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol. 2021 Nov 20;39(33):3671-3681. Epub 2021 Sep 2. link to original article contains dosing details in manuscript link to PMC article PubMed JapicCTI-153004
  18. CORAIL: Gaillard S, Oaknin A, Ray-Coquard I, Vergote I, Scambia G, Colombo N, Fernandez C, Alfaro V, Kahatt C, Nieto A, Zeaiter A, Aracil M, Vidal L, Pardo-Burdalo B, Papai Z, Kristeleit R, O'Malley DM, Benjamin I, Pautier P, Lorusso D. Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL). Gynecol Oncol. 2021 Nov;163(2):237-245. Epub 2021 Sep 11. link to original article contains dosing details in abstract PubMed NCT02421588
  19. AGO-OVAR 2.29: NCT03353831
  20. EPIK-O: NCT04729387
  21. NItCHE: NCT04679064
  22. PROCEEDOV: NCT01170650

Pegylated liposomal doxorubicin & Bevacizumab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)
ESMO-MCBS (4)
2009-2011 Phase 3 (E-RT-esc) 1a. Paclitaxel
1b. PLD
1c. Topotecan 		Superior PFS
Median PFS: 6.7 vs 3.4 mo
(HR 0.48, 95% CI 0.38-0.60)

Chemotherapy

Targeted therapy

28-day cycles

References

  1. AURELIA: 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 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains dosing details in manuscript PubMed NCT00976911
    1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. 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 May 1;32(13):1309-16. link to original article link to PMC article PubMed
    2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
  2. NItCHE: NCT04679064

Pegylated liposomal doxorubicin & Trabectedin

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Monk et al. 2010 (OVA-301)
ESMO-MCBS (2)
2005-2007 Phase 3 (E-esc) PLD Seems to have superior PFS (primary endpoint)
Median PFS: 7.3 vs 5.8 mo
(HR 0.79, 95% CI 0.65-0.96)

Might have superior OS1 (secondary endpoint)
Median OS: 22.2 vs 18.9 mo
(HR 0.86, 95% CI 0.72-1.02)

1Reported efficacy is based on the 2012 update.

Chemotherapy

21-day cycles

References

  1. OVA-301: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Lisyanskaya AS, Makhson AN, Rolski J, Gorbounova VA, Ghatage P, Bidzinski M, Shen K, Ngan HY, Vergote IB, Nam JH, Park YC, Lebedinsky CA, Poveda AM. Trabectedin plus pegylated liposomal Doxorubicin in recurrent ovarian cancer. J Clin Oncol. 2010 Jul 1;28(19):3107-14. Epub 2010 Jun 1. link to original article contains dosing details in abstract PubMed NCT00113607
    1. PRO analysis: Krasner CN, Poveda A, Herzog TJ, Vermorken JB, Kaye SB, Nieto A, Claret PL, Park YC, Parekh T, Monk BJ. Patient-reported outcomes in relapsed ovarian cancer: results from a randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone. Gynecol Oncol. 2012 Oct;127(1):161-7. Epub 2012 Jul 2. link to original article PubMed
    2. Update: 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 Oct;48(15):2361-8. Epub 2012 Apr 26. link to original article PubMed

Pemetrexed monotherapy

Regimen variant #1, 700 mg/m2

Study Dates of enrollment Evidence
Miller et al. 2009 (GOG-0126Q) 2004-2006 Phase 2

Note: this is the dosage for patients with previous radiation therapy.

Chemotherapy

Supportive therapy

  • Folic acid 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy
  • Cyanocobalamin (Vitamin B12) 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM once every 9 weeks
  • Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
  • No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed

21-day cycles


Regimen variant #2, 900 mg/m2

Study Dates of enrollment Evidence
Miller et al. 2009 (GOG-0126Q) 2004-2006 Phase 2

Chemotherapy

Supportive therapy

  • Folic acid 350 to 600 mcg PO once per day, starting 7 days prior to pemetrexed, to continue throughout therapy
  • Cyanocobalamin (Vitamin B12) 1000 mcg IM once, 7 days prior to pemetrexed, then 1000 mcg IM once every 9 weeks
  • Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after pemetrexed
  • No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed

21-day cycles

References

  1. GOG-0126Q: Miller DS, Blessing JA, Krasner CN, Mannel RS, Hanjani P, Pearl ML, Waggoner SE, Boardman CH; Gynecologic Oncology Group. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol. 2009 Jun 1;27(16):2686-91. Epub 2009 Mar 30. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00087087

Topotecan monotherapy

Regimen variant #1, 4 mg/m2, 3 weeks out of 4 x 12 mo

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sehouli et al. 2010 (TOWERov) 2005-2008 Randomized Phase 2 (E-switch-ic) Topotecan; q3wk Did not meet primary endpoint of CBR
Pujade-Lauraine et al. 2014 (AURELIA) 2009-2011 Phase 3 (C) 1a. Paclitaxel & Bevacizumab
1b. PLD & Bevacizumab
1c. Topotecan & Bevacizumab 		Inferior PFS

Note: TOWER should not be confused with the trial by the same name in B-ALL.

Chemotherapy

28-day cycle for up to 13 cycles (1 year)


Regimen variant #2, 4 mg/m2, 3 weeks out of 4, indefinite

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) 2009-2011 Phase 3 (C) 1a. Paclitaxel & Bevacizumab
1b. PLD & Bevacizumab
1c. Topotecan & Bevacizumab 		Inferior PFS
Moore et al. 2021 (FORWARD I) 2017-2018 Phase 3 (C) Mirvetuximab soravtansine Did not meet primary endpoint of PFS

Biomarker eligibility criteria

  • FORWARD I: High folate receptor-alpha expression

Chemotherapy

28-day cycles


Regimen variant #3, 6.25 mg/m2, split dosing, q3wk x 12 mo

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sehouli et al. 2010 (TOWERov) 2005-2008 Randomized Phase 2 (C) Topotecan; weekly Did not meet primary endpoint of CBR

Note: TOWER should not be confused with the trial by the same name in B-ALL.

Chemotherapy

21-day cycle for up to 18 cycles (1 year)


Regimen variant #4, 6.25 mg/m2, split dosing, q3wk, indefinite

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sehouli et al. 2008 1999-2004 Phase 3 (C) 1. Etoposide & Topotecan
2. Gemcitabine & Topotecan 		Did not meet primary endpoint of OS
Meier et al. 2009 (AGO-OVAR 2.3) 1998-2002 Phase 3 (E-switch-ic) Treosulfan Superior OS
Pujade-Lauraine et al. 2014 (AURELIA) 2009-2011 Phase 3 (C) 1a. Paclitaxel & Bevacizumab
1b. PLD & Bevacizumab
1c. Topotecan & Bevacizumab 		Inferior PFS
Kurzeder et al. 2016 (PENELOPE) 2013-2014 Phase 3 (C) 1a. Gemcitabine & Pertuzumab
1b. Paclitaxel & Pertuzumab
1c. Topotecan & Pertuzumab 		Did not meet primary endpoint of PFS
Moore et al. 2021 (FORWARD I) 2017-2018 Phase 3 (C) Mirvetuximab soravtansine Did not meet primary endpoint of PFS
Awaiting publication (NItCHE) 2020-ongoing Phase 3 (C) Niraparib & Dostarlimab TBD

Note: this was the dosing used in third-line therapy in AGO-OVAR 2.3.

Biomarker eligibility criteria

  • FORWARD I: High folate receptor-alpha expression

Chemotherapy

21-day cycles


Regimen variant #5, 7.5 mg/m2, split dosing, q3wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bookman et al. 1996 NR Phase 2 (RT)
ten Bokkel Huinink et al. 1997 NR Randomized (E-RT-switch-ic) Paclitaxel Might have superior TTP1
Gordon et al. 2001 (Doxil Study 30-49) 1997-1999 Phase 3 (C) PLD Might have inferior PFS
Meier et al. 2009 (AGO-OVAR 2.3) 1998-2002 Phase 3 (E-switch-ic) Treosulfan Superior OS
Gaillard et al. 2021 (CORAIL) 2015-06-26 to 2018-10-12 Phase 3 (C) Lurbinectedin Did not meet primary endpoint of PFS

1Reported efficacy for ten Bokkel Huinink et al. 1997 is based on the 2004 update.
Note: this was the dosing used in second-line therapy in AGO-OVAR 2.3.

Chemotherapy

21-day cycles

References

  1. Bookman MA, Malmström H, Bolis G, Gordon A, Lissoni A, Krebs JB, Fields SZ. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol. 1998 Oct;16(10):3345-52. link to original article PubMed
  2. ten Bokkel Huinink W, Gore M, Carmichael J, Gordon A, Malfetano J, Hudson I, Broom C, Scarabelli C, Davidson N, Spanczynski M, Bolis G, Malmström H, Coleman R, Fields SC, Heron JF. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer. J Clin Oncol. 1997 Jun;15(6):2183-93. link to original article contains dosing details in abstract PubMed
    1. Update: ten Bokkel Huinink W, Lane SR, Ross GA; International Topotecan Study Group. Long-term survival in a phase III, randomised study of topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Ann Oncol. 2004 Jan;15(1):100-3. link to original article PubMed
  3. Doxil Study 30-49: Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001 Jul 15;19(14):3312-22. link to original article PubMed
    1. Update: Gordon AN, Tonda M, Sun S, Rackoff W; Doxil Study 30-49 Investigators. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol. 2004 Oct;95(1):1-8. link to original article contains dosing details in manuscript PubMed
  4. Sehouli J, Stengel D, Oskay-Oezcelik G, Zeimet AG, Sommer H, Klare P, Stauch M, Paulenz A, Camara O, Keil E, Lichtenegger W; North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2008 Jul 1;26(19):3176-82. link to original article contains dosing details in manuscript PubMed
  5. AGO-OVAR 2.3: Meier W, du Bois A, Reuss A, Kuhn W, Olbricht S, Gropp M, Richter B, Lück HJ, Kimmig R, Pfisterer J. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy: a prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol. 2009 Aug;114(2):199-205. Epub 2009 May 14. link to original article contains dosing details in supplement PubMed
  6. TOWER: Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T, Markmann S, Mahner S, Mueller L, Lorenz R, Nugent A, Wilke J, Kuznik A, Doering G, Wischnik A, Sommer H, Meerpohl HG, Schroeder W, Lichtenegger W, Oskay-Oezcelik G; North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. 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 Jan 10;29(2):242-8. Epub 2010 Nov 29. link to original article contains dosing details in manuscript PubMed NCT00170677
  7. AURELIA: 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 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains dosing details in manuscript PubMed NCT00976911
    1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. 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 May 1;32(13):1309-16. link to original article link to PMC article PubMed
    2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
  8. PENELOPE: Kurzeder C, Bover I, Marmé F, Rau J, Pautier P, Colombo N, Lorusso D, Ottevanger P, Bjurberg M, Marth C, Barretina-Ginesta P, Vergote I, Floquet A, Del Campo JM, Mahner S, Bastière-Truchot L, Martin N, Oestergaard MZ, Kiermaier A, Schade-Brittinger C, Polleis S, du Bois A, Gonzalez-Martin A. Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-expressing platinum-resistant ovarian cancer (PENELOPE). J Clin Oncol. 2016 Jul 20;34(21):2516-25. Epub 2016 Jun 6. link to original article contains dosing details in manuscript PubMed NCT01684878
    1. Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
  9. FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article contains dosing details in manuscript PubMed NCT02631876
  10. CORAIL: Gaillard S, Oaknin A, Ray-Coquard I, Vergote I, Scambia G, Colombo N, Fernandez C, Alfaro V, Kahatt C, Nieto A, Zeaiter A, Aracil M, Vidal L, Pardo-Burdalo B, Papai Z, Kristeleit R, O'Malley DM, Benjamin I, Pautier P, Lorusso D. Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL). Gynecol Oncol. 2021 Nov;163(2):237-245. Epub 2021 Sep 11. link to original article contains dosing details in abstract PubMed NCT02421588
  11. NItCHE: NCT04679064

Topotecan & Bevacizumab

Regimen variant #1, topotecan 3 weeks out of 4

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)
ESMO-MCBS (4)
2009-2011 Phase 3 (E-RT-esc) 1a. Paclitaxel
1b. PLD
1c. Topotecan 		Superior PFS
Median PFS: 6.7 vs 3.4 mo
(HR 0.48, 95% CI 0.38-0.60)

Chemotherapy

Targeted therapy

28-day cycles


Regimen variant #2, topotecan 6.25 mg/m2, split dosing, q3wk

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA)
ESMO-MCBS (4)
2009-2011 Phase 3 (E-RT-esc) 1a. Paclitaxel
1b. PLD
1c. Topotecan 		Superior PFS
Median PFS: 6.7 vs 3.4 mo
(HR 0.48, 95% CI 0.38-0.60)

Chemotherapy

Targeted therapy

21-day cycles

References

  1. AURELIA: 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 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains dosing details in manuscript PubMed NCT00976911
    1. PRO analysis: Stockler MR, Hilpert F, Friedlander M, King MT, Wenzel L, Lee CK, Joly F, de Gregorio N, Arranz JA, Mirza MR, Sorio R, Freudensprung U, Sneller V, Hales G, Pujade-Lauraine E. 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 May 1;32(13):1309-16. link to original article link to PMC article PubMed
    2. Subgroup analysis: Sorio R, Roemer-Becuwe C, Hilpert F, Gibbs E, García Y, Kaern J, Huizing M, Witteveen P, Zagouri F, Coeffic D, Lück HJ, González-Martín A, Kristensen G, Levaché CB, Lee CK, Gebski V, Pujade-Lauraine E; AURELIA Investigators. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of the randomised phase III AURELIA trial. Gynecol Oncol. 2017 Jan;144(1):65-71. Epub 2016 Nov 18. link to original article PubMed
  2. NItCHE: NCT04679064

Trabectedin monotherapy

Regimen

Study Dates of enrollment Evidence
Krasner et al. 2007 2002-2004 Phase 2

Chemotherapy

Supportive therapy

28-day cycles

References

  1. Krasner CN, McMeekin DS, Chan S, Braly PS, Renshaw FG, Kaye S, Provencher DM, Campos S, Gore ME. A phase II study of trabectedin single agent in patients with recurrent ovarian cancer previously treated with platinum-based regimens. Br J Cancer. 2007 Dec 17;97(12):1618-24. Epub 2007 Nov 13. link to original article link to PMC article contains dosing details in manuscript PubMed

Treosulfan monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Meier et al. 2009 (AGO-OVAR 2.3) 1998-2002 Phase 3 (E-switch-ic) Topotecan Inferior OS
Sehouli et al. 2016 2002-2014 Phase 3b (C) Treosulfan; PO Might have superior OS

Chemotherapy

  • Treosulfan (Ovastat) by the following laboratory-based criteria:
    • CrCl greater than 40: 7000 mg/m2 IV once on day 1
    • CrCl 20 to 40: 6000 mg/m2 IV once on day 1
    • CrCl less than 20: 5000 mg/m2 IV once on day 1

28-day cycles

References

  1. AGO-OVAR 2.3: Meier W, du Bois A, Reuss A, Kuhn W, Olbricht S, Gropp M, Richter B, Lück HJ, Kimmig R, Pfisterer J. Topotecan versus treosulfan, an alkylating agent, in patients with epithelial ovarian cancer and relapse within 12 months following 1st-line platinum/paclitaxel chemotherapy: a prospectively randomized phase III trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR). Gynecol Oncol. 2009 Aug;114(2):199-205. Epub 2009 May 14. link to original article contains dosing details in supplement PubMed
  2. Sehouli J, Tomè O, Dimitrova D, Camara O, Runnebaum IB, Tessen HW, Rautenberg B, Chekerov R, Muallem MZ, Lux MP, Trarbach T, Gitsch G. A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO). J Cancer Res Clin Oncol. 2017 Mar;143(3):541-550. Epub 2016 Nov 28. link to original article link to PMC article contains dosing details in manuscript PubMed

Vinorelbine monotherapy

Regimen

Study Dates of enrollment Evidence
Rothenberg et al. 2004 1995-03 to 1997-07 Phase 2

Chemotherapy

21-day cycles

References

  1. Rothenberg ML, Liu PY, Wilczynski S, Nahhas WA, Winakur GL, Jiang CS, Moinpour CM, Lyons B, Weiss GR, Essell JH, Smith HO, Markman M, Alberts DS; SWOG. Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study. Gynecol Oncol. 2004 Dec;95(3):506-12. link to original article contains dosing details in abstract PubMed

Investigational agents

These are drugs under study with at least some promising results for this disease.

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