Ovarian cancer

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Summer B. Dewdney, MD
Rush University
Chicago, IL

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50 regimens on this page
91 variants on this page

Contents


Guidelines

ESMO

Older

ESMO/ESGO

NCCN

SGO/ASCO

Adjuvant therapy for early stage disease

Carboplatin monotherapy

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Variant #1, AUC 5

Study Evidence Comparator Comparative Efficacy
Colombo et al. 2003 (ICON1) Phase III (E) Observation Superior OS (*)

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

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles

Variant #2, 350 mg/m2

Study Evidence Comparator Comparative Efficacy
Trimbos et al. 2003 (ACTION) Phase III (E) Observation Superior OS (*)

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. Reported efficacy is based on the 2003 pooled update.

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 analysis: Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; European Organisation for Research and Treatment of Cancer 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; International Collaborative Ovarian Neoplasm (ICON) collaborators. 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
    1. Pooled analysis: Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; European Organisation for Research and Treatment of Cancer 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

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Regimen

Study Evidence Comparator Comparative Efficacy
Bell et al. 2006 (GOG 157) Phase III (C) CP x 6 Seems not superior

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 protocol 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 PubMed

Observation

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Regimen

Study Evidence Comparator Comparative Efficacy
Young et al. 1990 Phase III (C) Melphalan Seems not superior
Trimbos et al. 2003 (ACTION) Phase III (C) Platinum-based chemotherapy Inferior OS (*)
Colombo et al. 2003 (ICON1) Phase III (C) Platinum-based chemotherapy Inferior OS (*)
Mannel et al. 2011 (GOG-0175) Phase III (C) Paclitaxel maint. Seems not superior

No further treatment. Reported efficacy for ACTION and ICON1 is based on the 2003 pooled update.

Preceding treatment

References

  1. Young RC, Walton LA, Ellenberg SS, Homesley HD, Wilbanks GD, Decker DG, Miller A, Park R, Major F Jr. Adjuvant therapy in stage I and stage II epithelial ovarian cancer: results of two prospective randomized trials. N Engl J Med. 1990 Apr 12;322(15):1021-7. link to original article PubMed
  2. 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 analysis: Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; European Organisation for Research and Treatment of Cancer 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
  3. ICON1: Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM, Torri V, Williams C, Lissoni A, Bonazzi C; International Collaborative Ovarian Neoplasm (ICON) collaborators. 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
    1. Pooled analysis: Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, Vermorken JB, Torri V, Mangioni C, Pecorelli S, Lissoni A, Swart AM; International Collaborative Ovarian Neoplasm 1; European Organisation for Research and Treatment of Cancer 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
  4. 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 PubMed

Neoadjuvant chemotherapy for advanced stage disease

Carboplatin & Paclitaxel

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Variant #1, AUC 5/175 x 3

Study Evidence Comparator Comparative Efficacy
Kehoe et al. 2015 (CHORUS) Phase III (E) Adjuvant Carboplatin & Paclitaxel 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

Variant #2, AUC 5/175 x 6

Study Evidence Comparator Comparative Efficacy Comparative Toxicity
Fagotti et al. 2016 (SCORPION) Phase III (E) Adjuvant Carboplatin & Paclitaxel Seems not superior Superior QoL

Chemotherapy

21-day cycle for 6 cycles

Subsequent treatment

Variant #3, AUC 6/175 x 3

Study Evidence Comparator Comparative Efficacy
Vergote et al. 2010 (EORTC 55971) Phase III (E) Adjuvant Carboplatin & Paclitaxel Non-inferior OS
Kehoe et al. 2015 (CHORUS) Phase III (E) Adjuvant Carboplatin & Paclitaxel 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; European Organization for Research and Treatment of Cancer-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 protocol in supplement PubMed
  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 protocol PubMed
  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 verified protocol PubMed

First-line chemotherapy for advanced stage disease

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

Carboplatin monotherapy

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Variant #1, AUC 5

Study Evidence Comparator Comparative Efficacy Comparative Toxicity
Parmar et al. 1998 (ICON2) Phase III (E) CAP Seems not superior Less toxic
Parmar et al. 2002 (ICON3) Phase III (C) 1. CAP
2. Carboplatin & Paclitaxel
Seems not superior

Chemotherapy

21-day cycle for 6 cycles

Variant #2, AUC 6, q3wk

Study Evidence Comparator Comparative Efficacy
Parmar et al. 2002 (ICON3) Phase III (C) 1. CAP
2. Carboplatin & Paclitaxel
Seems not superior
Banerjee et al. 2012 (SCOTROC 4) Phase III (C) Dose-escalated Carboplatin Seems not superior

Chemotherapy

21-day cycle for 6 cycles

Variant #3, AUC 6, q4wk

Study Evidence Comparator Comparative Efficacy
Gore et al. 1998 Phase III (C) Carboplatin AUC 12 x 4 Seems not superior

Chemotherapy

28-day cycle for 6 cycles

Variant #4, AUC 9

Study Evidence Comparator Comparative Efficacy
Markman et al. 2001 (GOG 114) Phase III (E) See link See link

Preceding treatment

Chemotherapy

28-day cycle for 2 cycles

Subsequent treatment

Variant #5, 400 mg/m2, q4wk

Study Evidence Comparator Comparative Efficacy
Mangioni et al. 1989 Phase III (C) Cisplatin Seems not superior
Taylor AE et al. 1994 Phase III (C) Cisplatin Seems not superior

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 protocol 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 protocol 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 protocol 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 Collaborators. 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 verified protocol 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 protocol 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. 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 protocol PubMed

Carboplatin & Docetaxel

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Regimen

Study Evidence Comparator Comparative Efficacy
Vasey et al. 2004 Phase III (E) Carboplatin & Paclitaxel Seems not superior

Preceding treatment

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  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 verified protocol PubMed

Carboplatin & Doxorubicin liposomal

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Regimen

Study Evidence Comparator Comparative Efficacy
Pignata et al. 2006 (MITO-2) Phase III (E) Carboplatin & Paclitaxel Seems not superior

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 medications

  • "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 Investigators. 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. contains verified protocol link to PMC article PubMed
    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 verified protocol PubMed

Carboplatin & Gemcitabine

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Regimen

Study Evidence Comparator Comparative Efficacy
Gordon et al. 2011 Phase III (E) Carboplatin & Paclitaxel Seems not superior

Chemotherapy

21-day cycle for up to 6 cycles

Subsequent treatment

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 verified protocol PubMed

Carboplatin & Paclitaxel

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

Variant #1, q1wk AUC 2/60

Study Evidence Comparator Comparative Efficacy
Pignata et al. 2014 (MITO-7) Phase III (E) TC, q3wk AUC 6/175 Seems not superior

Chemotherapy

21-day cycle for 6 cycles

Variant #2, q3wk AUC 5/175

Study Evidence Comparator Comparative Efficacy Comparative Toxicity
Neijt et al. 2000 Phase III (E) Cisplatin & Paclitaxel Seems not superior
Vasey et al. 2004 Phase III (C) Carboplatin & Docetaxel Seems not superior
du Bois et al. 2006 (AGO-OVAR 5) Phase III (C) TEC Seems not superior
Möbus et al. 2007 Phase III (C) High-dose chemotherapy with auto HSCT Seems not superior
Pignata et al. 2006 (MITO-2) Phase III (C) Carboplatin & Pegylated liposomal doxorubicin Seems not superior
du Bois et al. 2010 (AGO-OVAR 9) Phase III (C) TCG Seems not superior
Hoskins et al. 2010 Phase III (C) Cisplatin & Topotecan, then Carboplatin & Paclitaxel Seems not superior Less toxic
Lindemann et al. 2012 Phase III (C) TEC Seems not superior
du Bois et al. 2015 (AGO-OVAR 12) Phase III (C) Carboplatin, Nintedanib, Paclitaxel Seems to have inferior PFS
Fagotti et al. 2016 (SCORPION) Phase III (C) Neoadjuvant Carboplatin & Paclitaxel Seems not superior Inferior QoL
Vergote et al. 2019 (TRINOVA-3) Phase III (C) Carboplatin, Paclitaxel, Trebananib Seems not superior

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 medications

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

Variant #3, q3wk AUC 6, q1wk 80 ("dose-dense")

Study Evidence Comparator Comparative Efficacy
Katsumata et al. 2009 (JGOG 3016) Phase III (E) TC, q3wk AUC 6/180 Seems to have superior OS

Chemotherapy

Supportive medications

  • "Standard premedication"

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

Variant #4, q3wk AUC 6/175

Study Evidence Comparator Comparative Efficacy
Alberts et al. 2008 (GRACES) Phase III (C) CP & IFN gamma-1b Seems not superior
Lhommé et al. 2008 Phase III (C) Paclitaxel & Valspodar Seems not superior
Bookman et al. 2009 (ICON5) Phase III (C) 1. TC & Gemcitabine
2. TC & PLD
3. TC & Topotecan
Seems not superior
Vergote et al. 2010 (EORTC 55971) Phase III (C) TC x 3, interval debulking, TC x 3 Non-inferior OS
Gordon et al. 2011 Phase III (C) Carboplatin & Gemcitabine Seems not superior
Burger et al. 2011 (GOG-0218) Phase III (C) 1. Carboplatin, Paclitaxel, Bevacizumab x 6 Seems not superior
2. Carboplatin, Paclitaxel, Bevacizumab x 6, then Bev maintenance Inferior PFS
Perren et al. 2011 (ICON7) Phase III (C) Carboplatin, Paclitaxel, Bevacizumab Seems not superior (*)
Pignata et al. 2014 (MITO-7) Phase III (C) TC, q1wk AUC 2/60 Seems not superior
du Bois et al. 2015 (AGO-OVAR 12) Phase III (C) Carboplatin, Nintedanib, Paclitaxel Seems to have inferior PFS
Chan et al. 2016 (GOG-0262) Phase III (C) TC, dose-dense Seems not superior
Sugiyama et al. 2016 (JGOG3017/GCIG) Phase III (C) Cisplatin & Irinotecan Seems not superior
Vergote et al. 2019 (TRINOVA-3) Phase III (C) Carboplatin, Paclitaxel, Trebananib Seems not superior

Note: reported efficacy for ICON7 is based on the 2015 update.

Chemotherapy

21-day cycle for up to 8 cycles

Subsequent treatment

Variant #5, q3wk AUC 6/180

Study Evidence Comparator Comparative Efficacy
Katsumata et al. 2009 (JGOG 3016) Phase III (C) TC, dose-dense Seems to have inferior OS

Chemotherapy

Supportive medications

  • "Standard premedication"

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

Variant #6, AUC 6/185

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

Preceding treatment

Chemotherapy

21-day cycle for 6 or more cycles

Variant #7, q3wk AUC 7/175

Study Evidence Comparator Comparative Efficacy
Aravantinos et al. 2005 Phase III (C) CP/Cisplatin & Paclitaxel Seems not superior
Aravantinos et al. 2008 Phase III (C) Cisplatin, Doxorubicin, Paclitaxel Might have inferior PFS

Chemotherapy

21-day cycle for 6 cycles

Variant #8, q3wk AUC 7.5/175

Study Evidence Comparator Comparative Efficacy
Ozols et al. 2003 (GOG 158) Phase III (E) Cisplatin & Paclitaxel Seems to have non-inferior RFS

Chemotherapy

Supportive medications

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 verified protocol 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 verified protocol 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 verified protocol PubMed
  4. 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 verified protocol PubMed
  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 protocol 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 protocol PubMed
  7. 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 verified protocol PubMed
  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 Investigators. 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. contains verified protocol link to PMC article PubMed
    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 verified protocol 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 verified protocol 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 study. 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 protocol 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. 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 verified protocol PubMed
  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 verified protocol PubMed
    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 protocol PubMed
  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; European Organization for Research and Treatment of Cancer-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 protocol in supplement PubMed
  16. 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 protocol PubMed
  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 verified protocol 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 verified protocol 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; ICON7 Investigators. 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 verified protocol PubMed
    1. 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; ICON7 trial investigators. 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. 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. 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 protocol PubMed
  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; Multicentre Italian Trials in Ovarian cancer (MITO-7); Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens et du sein (GINECO); Mario Negri Gynecologic Oncology (MaNGO); European Network of Gynaecological Oncological Trial Groups (ENGOT-OV-10); Gynecologic Cancer InterGroup (GCIG) Investigators. 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
  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 protocol PubMed
  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 verified protocol 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 verified protocol PubMed
  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 verified protocol PubMed
  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 protocol PubMed
  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 protocol PubMed

Carboplatin, Paclitaxel, Bevacizumab

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

Variant #1, q3wk paclitaxel, standard-dose bevacizumab

FDA-recommended dose
Study Evidence Comparator Comparative Efficacy
Burger et al. 2011 (GOG-0218) Phase III (E) Carboplatin & Paclitaxel Superior PFS (*)
Chan et al. 2016 (GOG-0262) Phase III (C) TC-Bev, dose-dense Seems not superior

Note: superior efficacy in GOG-0218 was only demonstrated in the arm that went on to receive bevacizumab maintenance. Decision to use bevacizumab in GOG-0262 was at the discretion of the patient; it was not a randomization.

Chemotherapy

21-day cycle for 6 cycles

Subsequent treatment

Variant #2, q3wk paclitaxel, low-dose bevacizumab

Study Evidence Comparator Comparative Efficacy
Perren et al. 2011 (ICON7) Phase III (E) Carboplatin & Paclitaxel Seems not superior (*)

Note: reported efficacy is based on the 2015 update.

Chemotherapy

  • Carboplatin (Paraplatin) 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) 175 mg/m2 IV over 3 hours once on day 1
  • Bevacizumab (Avastin) as follows:
    • Cycle 1: not given if chemotherapy starts within 4 weeks of surgery. If greater than 4 weeks after surgery: 7.5 mg/kg IV once on day 1
    • Cycles 2 to 6: 7.5 mg/kg IV once on day 1

21-day cycle for 6 cycles

Subsequent treatment

Variant #3, weekly paclitaxel

Study Evidence Comparator Comparative Efficacy
Walker et al. 2019 (GOG-252) Phase III (C) 1. IP Carboplatin, IV Paclitaxel, Bevacizumab
2. IP Cisplatin, IV/IP Paclitaxel, Bevacizumab
Seems not superior

Chemotherapy

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 verified protocol 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; ICON7 Investigators. 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 verified protocol PubMed
    1. 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; ICON7 trial investigators. 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 verified protocol PubMed
  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 verified protocol link to PMC article PubMed

Cisplatin & Paclitaxel

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

Variant #1, 75/135

Study Evidence Comparator Comparative Efficacy
McGuire et al. 1996 (GOG 111) Phase III (E) Cisplatin & Cyclophosphamide Superior OS
Muggia et al. 2000 (GOG 132) Phase III (C) 1. Cisplatin
2. Paclitaxel
Seems not superior
Markman et al. 2001 (GOG 114) Phase III (C) Carboplatin, then IP Cisplatin & IV Paclitaxel Seems to have inferior OS
Ozols et al. 2003 (GOG 158) Phase III (C) Carboplatin & Paclitaxel Seems to have non-inferior RFS
Rose et al. 2004 (GOG 152) Phase III (C) Cisplatin & Paclitaxel, with interval debulking Seems not superior
Armstrong et al. 2006 (GOG 172) Phase III (C) IP Cisplatin & Paclitaxel Seems to have inferior OS
Spriggs et al. 2007 (GOG 162) Phase III (C) Cisplatin & prolonged-infusion Paclitaxel Seems not superior

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 once on day 1

Supportive medications

21-day cycle for 6 cycles

Variant #2, 75/175

Study Evidence Comparator Comparative Efficacy
Piccart et al. 2000 (OV10) Phase III (E) Cisplatin & Cyclophosphamide Superior OS
Neijt et al. 2000 Phase III (C) Carboplatin & Paclitaxel Seems not superior
Mouratidou et al. 2007 Phase III (E) Cisplatin & Cyclophosphamide Seems not superior
van der Burg et al. 2014 Phase III (C) Cisplatin & weekly Paclitaxel Seems not superior

Preceding treatment

Chemotherapy

21-day cycle for 6 or more cycles

Variant #3, 75/185

Study Evidence Comparator Comparative Efficacy Comparative Toxicity
du Bois et al. 2003 (AGO-OVAR 3) Phase III (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 verified protocol 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 verified protocol 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 verified protocol 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 verified protocol 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 protocol 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 verified protocol 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 verified protocol 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 verified protocol PubMed
  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 verified protocol PubMed
    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 verified protocol 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 protocol 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 protocol PubMed
  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 protocol PubMed

Intraperitoneal therapy

Cisplatin & Paclitaxel

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Variant #1, IV paclitaxel

Study Evidence Comparator Comparative Efficacy
Markman et al. 2001 (GOG 114) Phase III (E) See link See link

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles

Variant #2, IV/IP paclitaxel

Study Evidence Comparator Comparative Efficacy
Armstrong et al. 2006 (GOG 172) Phase III (E) IV Cisplatin & Paclitaxel 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 medications

  • (Varies per reference)
  • "Standard premedication" for Paclitaxel (Taxol)
  • "Hydration and antiemetic agents" before Cisplatin (Platinol)
  • 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 (Taxol)
  • 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 protocol 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 verified protocol PubMed
    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 verified protocol PubMed

Maintenance after first-line therapy

Altretamine monotherapy

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Regimen

Study Evidence
Rothenberg et al. 2001 (SWOG-9326) Phase II

Chemotherapy

28-day cycle for 6 cycles

References

  1. 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 protocol 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. PubMed

Bevacizumab monotherapy

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Variant #1, 12 cycles

Study Evidence
Perren et al. 2011 (ICON7) Non-randomized portion 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

Chemotherapy

21-day cycle for 12 cycles

Variant #2, 16 cycles

FDA-recommended dose
Study Evidence
Burger et al. 2011 (GOG-0218) Non-randomized portion of RCT
Walker et al. 2019 (GOG-252) Non-randomized portion 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. The FDA-recommended duration of treatment is 22 cycles (including the 6 cycles of combination chemotherapy).

Preceding treatment

Chemotherapy

21-day cycle for 16 cycles

Variant #3, indefinite

Study Evidence
Chan et al. 2016 (GOG-0262) Non-randomized portion 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

Chemotherapy

21-day cycles

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 verified protocol 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; ICON7 Investigators. 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 verified protocol PubMed
    1. 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; ICON7 trial investigators. 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 verified protocol PubMed
  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 verified protocol link to PMC article PubMed

Observation

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Regimen

Study Evidence Comparator Comparative Efficacy
Piccart et al. 2003 (EORTC 55875) Phase III (C) IP Cisplatin Seems not superior
De Placido et al. 2004 (MITO-1) Phase III (C) Topotecan Seems not superior
Hall et al. 2004 Phase III (C) IFN alfa-2a Seems not superior
Pfisterer et al. 2006 (AGO-OVAR 7) Phase III (C) Topotecan Seems not superior
Berek et al. 2008 Phase III (C) Oregovomab Seems not superior
Pecorelli et al. 2009 (After-6 protocol 1) Phase III (C) Paclitaxel Seems not superior
Vergote et al. 2013 (EORTC 55041) Phase III (C) Erlotinib Seems not superior

No further treatment.

Preceding treatment

  • AGO-OVAR 7: TC x 6-10
  • EORTC 55041: Debulking surgery (primary or interval) & platinum-based chemotherapy x 6 to 9, with SD or better

References

  1. EORTC 55875: Piccart MJ, Floquet A, Scarfone G, Willemse PH, Emerich J, Vergote I, Giurgea L, Coens C, Awada A, Vermorken JB. Intraperitoneal cisplatin versus no further treatment: 8-year results of EORTC 55875, a randomized phase III study in ovarian cancer patients with a pathologically complete remission after platinum-based intravenous chemotherapy. Int J Gynecol Cancer. 2003 Nov-Dec;13 Suppl 2:196-203. link to original article PubMed
  2. MITO-1: De Placido S, Scambia G, Di Vagno G, Naglieri E, Lombardi AV, Biamonte R, Marinaccio M, Cartenì G, Manzione L, Febbraro A, De Matteis A, Gasparini G, Valerio MR, Danese S, Perrone F, Lauria R, De Laurentiis M, Greggi S, Gallo C, Pignata S. Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study. J Clin Oncol. 2004 Jul 1;22(13):2635-42. link to original article PubMed
  3. Hall GD, Brown JM, Coleman RE, Stead M, Metcalf KS, Peel KR, Poole C, Crawford M, Hancock B, Selby PJ, Perren TJ. Maintenance treatment with interferon for advanced ovarian cancer: results of the Northern and Yorkshire gynaecology group randomised phase III study. Br J Cancer. 2004 Aug 16;91(4):621-6. link to original article link to PMC article PubMed
  4. AGO-OVAR 7: Pfisterer J, Weber B, Reuss A, Kimmig R, du Bois A, Wagner U, Bourgeois H, Meier W, Costa S, Blohmer JU, Lortholary A, Olbricht S, Stähle A, Jackisch C, Hardy-Bessard AC, Möbus V, Quaas J, Richter B, Schröder W, Geay JF, Lück HJ, Kuhn W, Meden H, Nitz U, Pujade-Lauraine E; AGO-OVAR; GINECO. Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO. J Natl Cancer Inst. 2006 Aug 2;98(15):1036-45. link to original article contains verified protocol PubMed
  5. Berek J, Taylor P, McGuire W, Smith LM, Schultes B, Nicodemus CF. Oregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer. J Clin Oncol. 2009 Jan 20;27(3):418-25. Epub 2008 Dec 15. link to original article PubMed
  6. After-6 protocol 1: Pecorelli S, Favalli G, Gadducci A, Katsaros D, Panici PB, Carpi A, Scambia G, Ballardini M, Nanni O, Conte P; After 6 Italian Cooperative Group. Phase III trial of observation versus six courses of paclitaxel in patients with advanced epithelial ovarian cancer in complete response after six courses of paclitaxel/platinum-based chemotherapy: final results of the After-6 protocol 1. J Clin Oncol. 2009 Oct 1;27(28):4642-8. Epub 2009 Aug 24. link to original article PubMed
  7. EORTC 55041: Vergote IB, Jimeno A, Joly F, Katsaros D, Coens C, Despierre E, Marth C, Hall M, Steer CB, Colombo N, Lesoin A, Casado A, Reinthaller A, Green J, Buck M, Ray-Coquard I, Ferrero A, Favier L, Reed NS, Curé H, Pujade-Lauraine E. Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group, and Gynecologic Cancer Intergroup study. J Clin Oncol. 2014 Feb 1;32(4):320-6. Epub 2013 Dec 23. link to original article PubMed

Olaparib monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Moore et al. 2018 (SOLO-1) Phase III (E) Placebo Superior PFS

Patients had BRCA1/2 mutations.

Chemotherapy

Continued indefinitely

References

  1. SOLO-1: Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018 Oct 21. [Epub ahead of print] link to original article contains protocol PubMed

Paclitaxel monotherapy

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Variant #1, 135 mg/m2 q4wk

Study Evidence
Gordon et al. 2011 Non-randomized portion of RCT

Preceding treatment

Chemotherapy

28-day cycle for up to 12 cycles

Variant #2, 175 mg/m2 q3wk x 3

Study Evidence
Micha et al. 2005 Phase II, <20 patients in this subgroup

Preceding treatment

  • Carboplatin, Gemcitabine, Paclitaxel x 6

Chemotherapy

21-day cycle for 3 cycles

Variant #3, 175 mg/m2 q3wk x 12

Study Evidence
Micha et al. 2005 Phase II, <20 patients in this subgroup

Preceding treatment

  • Carboplatin, Gemcitabine, Paclitaxel x 6

Chemotherapy

21-day cycle for 12 cycles

Variant #4, 175 mg/m2 q4wk x 3

Study Evidence Comparator Comparative Efficacy
Markman et al. 2003 (GOG 178) Phase III (C) Paclitaxel for 12 cycles Inferior PFS

Chemotherapy

28-day cycle for 3 cycles

Variant #5, 175 mg/m2 q4wk x 12

Study Evidence Comparator Comparative Efficacy
Markman et al. 2003 (GOG 178) Phase III (E) Paclitaxel for 3 cycles Superior PFS

Chemotherapy

28-day cycle for 12 cycles

References

  1. Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D; Southwest Oncology Group; 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 verified protocol PubMed
    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 verified protocol 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 verified protocol 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 verified protocol 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 verified protocol PubMed

Pazopanib monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Du Bois et al. 2014 (AGO-OVAR 16) Phase III (E) Placebo Superior PFS

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

Chemotherapy

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 verified protocol PubMed
    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

Placebo

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Regimen

Study Evidence Comparator Comparative Efficacy
Hirte et al. 2006 Phase III (C) Tanomastat Seems not superior
Sabbatini et al. 2013 (MIMOSA) Phase III (C) Abagovomab Seems not superior
Du Bois et al. 2014 (AGO-OVAR 16) Phase III (C) Pazopanib Inferior PFS

No active antineoplastic treatment after initial treatment.

Preceding treatment

  • MIMOSA: Debulking surgery, then platinum-taxane-based chemotherapy x 6 to 8, with CR
  • AGO-OVAR 16: Debulking surgery (primary or interval) & platinum-taxane-based chemotherapy for at least 5 cycles, with SD or better

References

  1. Hirte H, Vergote IB, Jeffrey JR, Grimshaw RN, Coppieters S, Schwartz B, Tu D, Sadura A, Brundage M, Seymour L. A phase III randomized trial of BAY 12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy: a National Cancer Institute of Canada Clinical Trials Group Study. Gynecol Oncol. 2006 Aug;102(2):300-8. Epub 2006 Jan 25. link to original article PubMed
  2. MIMOSA: Sabbatini P, Harter P, Scambia G, Sehouli J, Meier W, Wimberger P, Baumann KH, Kurzeder C, Schmalfeldt B, Cibula D, Bidzinski M, Casado A, Martoni A, Colombo N, Holloway RW, Selvaggi L, Li A, del Campo J, Cwiertka K, Pinter T, Vermorken JB, Pujade-Lauraine E, Scartoni S, Bertolotti M, Simonelli C, Capriati A, Maggi CA, Berek JS, Pfisterer J. Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO--the MIMOSA study. J Clin Oncol. 2013 Apr 20;31(12):1554-61. Epub 2013 Mar 11. link to original article link to PMC article PubMed
  3. 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 verified protocol PubMed
    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

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

Carboplatin monotherapy

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Variant #1, AUC 5

Study Evidence Comparator Comparative Efficacy
Parmar et al. 2003 (ICON4) Phase III (C) 1. Carboplatin & Paclitaxel
2. Cisplatin & Paclitaxel
Seems to have inferior OS
Pfisterer et al. 2006 (AGO-OVAR 2.5) Phase III (C) Carboplatin & Gemcitabine Inferior PFS

Chemotherapy

21-day cycle for 6 to 10 cycles

Variant #2, 300 mg/m2

Study Evidence Comparator Comparative Efficacy
Bolis et al. 2001 (ARGO 96) Phase III (C) Carboplatin & Epirubicin Seems not superior

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 (ARGO 96) 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 protocol 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 and AGO Collaborators. 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 verified protocol PubMed
  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 verified protocol PubMed

Carboplatin & Docetaxel

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

Study Evidence
Kushner et al. 2007 Phase II

Note: BSA was capped at 2 m2.

Chemotherapy

Supportive medications

28-day cycle for 6 cycles

Variant #2, AUC 5/75

Study Evidence Comparator Comparative Efficacy
Strauss et al. 2007 Phase II
Vergote et al. 2016 (MORAb-003-004) Phase III (C) Carboplatin, Docetaxel, Farletuzumab Seems not superior

Note: this is the lower bound of carboplatin dosing specified by MORAb-003-004.

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

Variant #3, AUC 6/75

Study Evidence Comparator Comparative Efficacy
Vergote et al. 2016 (MORAb-003-004) Phase III (C) Carboplatin, Paclitaxel, Farletuzumab Seems not superior

Note: this is the upper bound of carboplatin dosing specified by MORAb-003-004.

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 verified protocol 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 verified protocol PubMed
  3. MORAb-003-004: 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 verified protocol PubMed

Carboplatin & Doxorubicin liposomal

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

Regimen

Study Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2010 (CALYPSO) Phase III (E) Carboplatin & Paclitaxel Superior PFS
Sehouli et al. 2016 (HECTOR) Randomized Phase II (C) Carboplatin & Topotecan Seems not superior

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

Chemotherapy

Supportive medications

28-day cycle for 6 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 verified protocol PubMed
    1. Update: Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Lauraine EP. 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 verified protocol 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. 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 verified protocol PubMed

Carboplatin & Gemcitabine

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GC: Gemcitabine & Carboplatin

Variant #1, limited duration

Study Evidence Comparator Comparative Efficacy
Pfisterer et al. 2006 (AGO-OVAR 2.5) Phase III (E) Carboplatin Superior PFS
Aghajanian et al. 2012 (OCEANS) Phase III (C) Carboplatin, Gemcitabine, Bevacizumab, then Bev maintenance Inferior PFS

Chemotherapy

21-day cycle for 6 to 10 cycles

Variant #2, indefinite

Study Evidence Comparator Comparative Efficacy
Sehouli et al. 2016 (HECTOR) Randomized Phase II (C) Carboplatin & Topotecan Seems not superior

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 verified protocol PubMed
  2. 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 verified protocol link to PMC article PubMed
    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. 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. 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 verified protocol PubMed

Carboplatin, Gemcitabine, Bevacizumab

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Regimen

Study Evidence Comparator Comparative Efficacy
Aghajanian et al. 2012 (OCEANS) Phase III (E) See link See link

Chemotherapy

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

Subsequent treatment

References

  1. 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 verified protocol link to PMC article PubMed
    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

Carboplatin & Paclitaxel

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CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin

Variant #1, AUC 5/175, limited duration

Study Evidence Comparator Comparative Efficacy
Vergote et al. 2016 (MORAb-003-004) Phase III (C) Carboplatin, Paclitaxel, Farletuzumab Seems not superior
Coleman et al. 2017 (NRG/GOG-0213) Phase III (C) Carboplatin, Paclitaxel, Bevacizumab Might have inferior OS
Pignata et al. 2017 (MITO-8) Phase III (C) NPBC Seems not superior

Chemotherapy

Supportive medications

21-day cycle for 6 to 9 cycles

Subsequent treatment

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

Variant #2, AUC 5/175, indefinite

Study Evidence Comparator Comparative Efficacy
Parmar et al. 2003 (ICON4) Phase III (E) Carboplatin Seems to have superior OS
Pujade-Lauraine et al. 2010 (CALYPSO) Phase III (C) Carboplatin & PLD Inferior PFS
Oza et al. 2014 (D0810C00041) Randomized Phase II (C) Carboplatin, Olaparib, Paclitaxel Inferior PFS
Sehouli et al. 2016 (HECTOR) Randomized Phase II (C) Carboplatin & Topotecan Seems not superior
Coleman et al. 2017 (NRG/GOG-0213) Phase III (C) Carboplatin, Paclitaxel, Bevacizumab Might have inferior OS

Chemotherapy

Supportive medications

21-day cycles

Variant #3, AUC 6/175, limited duration

Study Evidence Comparator Comparative Efficacy
Vergote et al. 2016 (MORAb-003-004) Phase III (C) Carboplatin, Paclitaxel, Farletuzumab Seems not superior

Chemotherapy

21-day cycle for 6 cycles

Variant #4, AUC 6/175, indefinite

Study Evidence Comparator Comparative Efficacy
Oza et al. 2014 (D0810C00041) Randomized Phase II (C) Carboplatin, Olaparib, Paclitaxel Inferior PFS

Chemotherapy

Supportive medications

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 and AGO Collaborators. 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 verified protocol PubMed
  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 verified protocol PubMed
    1. Update: Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Lauraine EP. 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 verified protocol 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 protocol PubMed
  4. MORAb-003-004: 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
  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. 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 verified protocol PubMed
  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 protocol PubMed
  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 verified protocol PubMed

Carboplatin, Olaparib, Paclitaxel

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Regimen

Study Evidence Comparator Comparative Efficacy
Oza et al. 2014 (D0810C00041) Randomized Phase II (E) Carboplatin & Paclitaxel Superior PFS

Chemotherapy

21-day cycle for 6 cycles

Subsequent treatment

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 verified protocol PubMed

Cisplatin & Gemcitabine

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Regimen

Study Evidence
Rose et al. 2003 Phase II

Chemotherapy

Supportive medications

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 verified protocol PubMed

Cisplatin & Paclitaxel

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Regimen

Study Evidence Comparator Comparative Efficacy
Parmar et al. 2003 (ICON4) Phase III (E) Carboplatin Seems to have superior OS

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 and AGO Collaborators. 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 verified protocol PubMed

Etoposide monotherapy

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Regimen

Study Evidence Efficacy
Rose et al. 1998 Phase II 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. 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 verified protocol PubMed

nab-Paclitaxel monotherapy

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Regimen

Study Evidence
Teneriello et al. 2009 Phase II

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 verified protocol PubMed

Rucaparib monotherapy

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Regimen

Study Evidence
Swisher et al. 2016 (ARIEL2 Part 1) Phase II

Chemotherapy

28-day cycles

References

  1. ARIEL2 Part 1: Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. Epub 2016 Nov 28. link to original article contains verified protocol PubMed

Maintenance after second-line therapy for platinum-sensitive disease

Bevacizumab monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Aghajanian et al. 2012 (OCEANS) Phase III (E) See link See link

Preceding treatment

Chemotherapy

21-day cycles

References

  1. 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 verified protocol link to PMC article PubMed
    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

Niraparib monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Mirza et al. 2016 (NOVA) Phase III (E) Placebo Superior PFS

Preceding treatment

  • Platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.

Chemotherapy

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 verified protocol PubMed

Olaparib monotherapy

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Variant #1, 300 twice per day

Study Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2017 (SOLO2) Phase III (E) Placebo Superior PFS

Patients had platinum-sensitive relapsed disease and BRCA1/2 mutations.

Chemotherapy

Continued indefinitely

Variant #2, 400 twice per day

Study Evidence Comparator Comparative Efficacy
Ledermann et al. 2012 (Study 19) Randomized Phase II (E) Placebo Might have superior OS (*)
Oza et al. 2014 (D0810C00041) Non-randomized portion of RCT

Reported 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."

Preceding treatment

Chemotherapy

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 verified protocol PubMed
    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. 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 PubMed
  2. 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 protocol PubMed
  3. SOLO2: Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. Epub 2017 Jul 25. link to original article contains protocol PubMed

Placebo

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Regimen

Study Evidence Comparator Comparative Efficacy
Ledermann et al. 2012 (Study 19) Randomized Phase II (C) Olaparib Might have inferior OS (*)
Ledermann et al. 2016 (ICON6) Phase III (C) Cediranib Inferior PFS
Mirza et al. 2016 (NOVA) Phase III (C) Niraparib Inferior PFS
Pujade-Lauraine et al. 2017 (SOLO2) Phase III (C) Olaparib Inferior PFS
Coleman et al. 2017 (ARIEL3) Phase III (C) Rucaparib Inferior PFS

No further active antineoplastic treatment. Reported 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."

Preceding treatment

  • Platinum-based chemotherapy

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 verified protocol PubMed
    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. 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 PubMed
  2. ICON6: Ledermann JA, Embleton AC, Raja F, Perren TJ, Jayson GC, Rustin GJS, Kaye SB, Hirte H, Eisenhauer E, Vaughan M, Friedlander M, González-Martín A, Stark D, Clark E, Farrelly L, Swart AM, Cook A, Kaplan RS, Parmar MKB; ICON6 collaborators. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016 Mar 12;387(10023):1066-1074. Erratum in: Lancet. 2016 Apr 23;387(10029):1722. link to original article PubMed
  3. 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 verified protocol PubMed
  4. SOLO2: Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. Epub 2017 Jul 25. link to original article contains protocol PubMed
  5. ARIEL3: Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. Epub 2017 Sep 12. link to original article link to PMC article PubMed

Rucaparib monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Coleman et al. 2017 (ARIEL3) Phase III (E) Placebo Superior PFS

Preceding treatment

  • Platinum-containing chemotherapy

Chemotherapy

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 verified protocol link to PMC article PubMed

Relapsed or recurrent disease, platinum-resistant

Bevacizumab monotherapy

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Regimen

Study Evidence
Burger et al. 2007 Phase II
Cannistra et al. 2007 Phase II

Chemotherapy

21-day cycles

References

  1. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. 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 verified protocol 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 verified protocol PubMed

Docetaxel monotherapy

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Regimen

Study Evidence
Rose et al. 2003a Phase II

Chemotherapy

Supportive medications

21-day cycles

References

  1. Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, Moore DH. 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 verified protocol PubMed

Doxorubicin pegylated liposomal monotherapy

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Variant #1, 40 mg/m2

Study Evidence Comparator Comparative Efficacy
Ferrandina et al. 2008 (MITO-3) Phase III (E) Gemcitabine Might have inferior ORR
Pujade-Lauraine et al. 2014 (AURELIA) Phase III (C) Pegylated liposomal doxorubicin & Bevacizumab Inferior PFS
Lindemann et al. 2017 (Ovaresist) Phase III (C) Tamoxifen Superior PFS

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.

Chemotherapy

Supportive medications

28-day cycles

Variant #2, 50 mg/m2

Study Evidence Comparator Comparative Efficacy
Gordon et al. 2001 (Doxil Study 30-49) Phase III (E) Topotecan Might have superior PFS
Mutch et al. 2007 Phase III (C) Gemcitabine Seems not superior
Vergote et al. 2009 (ASSIST-1) Phase III (C) Canfosfamide Superior OS
Vergote et al. 2010 (ASSIST-5) Phase III (C) Canfosfamide & PLD Seems not superior
Monk et al. 2010 (OVA-301) Phase III (C) PLD & Trabectedin Might have inferior OS (*)
Colombo et al. 2012 Phase III (C) Patupilone Seems not superior
Marth et al. 2016 (TRINOVA-2) Phase III (C) PLD & Trebananib Seems not superior

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

Chemotherapy

28-day cycles

References

  1. 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 verified protocol PubMed
  2. 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 verified protocol PubMed content property of HemOnc.org
  3. 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 verified protocol PubMed
  4. 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 protocol PubMed
  5. 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
  6. 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 protocol PubMed
    1. 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 SD article PubMed
  7. 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 protocol PubMed
  8. 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. link to original article contains verified protocol PubMed
    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
  9. 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 protocol PubMed
  10. 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 protocol PubMed

Doxorubicin pegylated liposomal & Bevacizumab

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Regimen

Study Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) Phase III (E) Pegylated liposomal doxorubicin Superior PFS

Chemotherapy

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. link to original article contains verified protocol PubMed
    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

Doxorubicin pegylated liposomal & Gemcitabine

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Regimen

Study Evidence
Ferrandina et al. 2005 Phase II

Chemotherapy

Supportive medications

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 verified protocol PubMed

Doxorubicin pegylated liposomal & Trabectedin

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Regimen

Study Evidence Comparator Comparative Efficacy
Monk et al. 2010 (OVA-301) Phase III (E) Pegylated liposomal doxorubicin Might have superior OS (*)

Note: Reported 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 protocol PubMed
    1. 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 SD article PubMed

Etoposide monotherapy

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Regimen

Study Evidence Efficacy
Rose et al. 1998 Phase II 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. 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 verified protocol PubMed

Gemcitabine monotherapy

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Variant #1, 2 weeks out of 3

Study Evidence Comparator Comparative Efficacy
Mutch et al. 2007 Phase III (E) Pegylated liposomal doxorubicin Seems not superior
Kurzeder et al. 2016 (PENELOPE) Phase III (C) Gemcitabine & Pertuzumab Seems not superior

Chemotherapy

21-day cycles

Variant #2, 3 weeks out of 4

Study Evidence Comparator Comparative Efficacy
Ferrandina et al. 2008 (MITO-3) Phase III (E) Pegylated liposomal doxorubicin Might have superior ORR

Chemotherapy

28-day cycles

References

  1. 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 verified protocol PubMed
  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 verified protocol 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 verified protocol PubMed

Olaparib monotherapy

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Regimen

Study Evidence
Audeh et al. 2010 Phase II
Gelmon et al. 2011 Phase II
Kaufman et al. 2014 Phase II

Patients in Kaufman et al. 2014 were resistant to prior platinum-containing therapy.

Chemotherapy

Continued indefinitely

References

  1. Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet. 2010 Jul 24;376(9737):245-51. Epub 2010 Jul 6. link to original article contains verified protocol PubMed
  2. Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, Hirte H, Huntsman D, Clemons M, Gilks B, Yerushalmi R, Macpherson E, Carmichael J, Oza A. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011 Sep;12(9):852-61. Epub 2011 Aug 19. link to original article contains verified protocol PubMed
  3. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article contains verified protocol PubMed

Paclitaxel monotherapy

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Variant #1, 80 mg/m2 weekly

Study Evidence Comparator Comparative Efficacy
Markman et al. 2006 Phase II
Pujade-Lauraine et al. 2014 (AURELIA) Phase III (C) Paclitaxel & Bevacizumab Inferior PFS
Monk et al. 2014 (TRINOVA-1) Phase III (C) Paclitaxel & Trebananib Inferior PFS
Pignata et al. 2015 (MITO 11) Randomized Phase II (C) Paclitaxel & Pazopanib Inferior PFS
Kurzeder et al. 2016 (PENELOPE) Phase III (C) Paclitaxel & Pertuzumab Seems not superior
Lindemann et al. 2017 (Ovaresist) Phase III (C) Tamoxifen Superior 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 medications

28-day cycles

Variant #2, 175 mg/m2, q3wk

Study Evidence Comparator Comparative Efficacy
Eisenhauer et al. 1994 Phase III (E) Paclitaxel 135 mg/m2 Seems to have superior PFS
Gore et al. 1995 Non-randomized
ten Bokkel Huinink et al. 1997 Phase III (E) Topotecan Might have inferior TTP (*)
Cantù et al. 1999 Phase III (E) CAP Seems to have inferior OS
Omura et al. 2003 Phase III (C) Paclitaxel 250 mg/m2 Seems to have inferior ORR
Buda et al. 2004 Phase III (C) Epirubicin & Paclitaxel Seems not superior

Note: reported 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

Variant #3, 200 mg/m2, q3wk

Study Evidence Comparator Comparative Efficacy
Rosenberg et al. 2002 Phase III (C) Weekly paclitaxel 67 mg/m2 Seems not superior

Chemotherapy

21-day cycles

Variant #4, with range

Study Evidence
McGuire et al. 1989 Phase II
Kohn et al. 1994 Phase II

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 protocol 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 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 protocol 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 protocol PubMed
  9. Buda A, Floriani I, Rossi R, Colombo N, Torri V, Conte PF, Fossati R, Ravaioli A, Mangioni C. 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 verified protocol 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 verified protocol 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. link to original article contains verified protocol PubMed
    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
    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 11 investigators. 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 protocol PubMed
  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 verified protocol 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 protocol PubMed

Paclitaxel & Bevacizumab

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Regimen

Study Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) Phase III (E) Paclitaxel Superior PFS

Chemotherapy

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. link to original article contains verified protocol PubMed
    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

Paclitaxel & Pazopanib

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Regimen

Study Evidence Comparator Comparative Efficacy
Pignata et al. 2015 (MITO 11) Randomized Phase II (E) Paclitaxel Superior PFS

Chemotherapy

21-day cycles

References

  1. Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO 11 investigators. 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 protocol PubMed

Pazopanib monotherapy

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Regimen

Study Evidence
Friedlander et al. 2010 Phase II

Chemotherapy

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 verified protocol PubMed

Pemetrexed monotherapy

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Variant #1, 700 mg/m2

Study Evidence
Miller et al. 2009 Phase II

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

Chemotherapy

Supportive medications

21-day cycles

Variant #2, 900 mg/m2

Study Evidence
Miller et al. 2009 Phase II

Chemotherapy

Supportive medications

21-day cycles

References

  1. Miller DS, Blessing JA, Krasner CN, Mannel RS, Hanjani P, Pearl ML, Waggoner SE, Boardman CH. 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 verified protocol link to PMC article PubMed

Topotecan monotherapy

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Variant #1, 4 mg/m2, 3 weeks out of 4

Study Evidence Comparator Comparative Efficacy
Sehouli et al. 2011 (TOWERov) Randomized Phase II (E) 5-day topotecan Seems not superior
Pujade-Lauraine et al. 2014 (AURELIA) Phase III (C) Bevacizumab & Topotecan 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 12 months (TOWER) or indefinitely (AURELIA)

Variant #2, 6.25 mg/m2, split dosing, q3wk

Study Evidence Comparator Comparative Efficacy
Sehouli et al. 2008 Phase III (C) 1. Etoposide & Topotecan
2. Gemcitabine & Topotecan
Seems not superior
Meier et al. 2009 (AGO-OVAR 2.3) Phase III (E) Treosulfan Superior OS
Sehouli et al. 2011 (TOWERov) Randomized Phase II (C) Weekly topotecan Seems not superior
Pujade-Lauraine et al. 2014 (AURELIA) Phase III (C) Topotecan & Bevacizumab Inferior PFS
Kurzeder et al. 2016 (PENELOPE) Phase III (C) Topotecan & Pertuzumab Seems not superior

Note: this was the dosing used in third-line therapy in AGO-OVAR 2.3.TOWER should not be confused with the trial by the same name in B-ALL.

Chemotherapy

21-day cycle for up to 12 months (TOWER) or indefinitely (AGO-OVAR 2.3; AURELIA; PENELOPE)

Variant #3, 7.5 mg/m2, split dosing, q3wk

Study Evidence Comparator Comparative Efficacy
Gordon et al. 2001 (Doxil Study 30-49) Phase III (C) Pegylated liposomal doxorubicin Might have inferior PFS
Meier et al. 2009 (AGO-OVAR 2.3) Phase III (E) Treosulfan Superior OS

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

Chemotherapy

21-day cycles

References

  1. 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 verified protocol PubMed
  2. Sehouli J, Stengel D, Oskay-Oezcelik G, Zeimet AG, Sommer H, Klare P, Stauch M, Paulenz A, Camara O, Keil E, Lichtenegger W. 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 verified protocol PubMed
  3. 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 verified protocol in supplement PubMed
  4. 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. 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 verified protocol PubMed
  5. 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. link to original article contains verified protocol PubMed
    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
  6. 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 verified protocol PubMed

Topotecan & Bevacizumab

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Variant #1, topotecan 3 weeks out of 4

Study Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) Phase III (E) Topotecan Superior PFS

Chemotherapy

28-day cycles

Variant #2, topotecan 6.25 mg/m2, split dosing, q3wk

Study Evidence Comparator Comparative Efficacy
Pujade-Lauraine et al. 2014 (AURELIA) Phase III (E) Topotecan Superior PFS

Chemotherapy

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. link to original article contains verified protocol PubMed
    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

Trabectedin monotherapy

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Regimen

Study Evidence
Krasner et al. 2007 Phase II

Chemotherapy

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 original article PubMed

Treosulfan monotherapy

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Regimen

Study Evidence Comparator Comparative Efficacy
Meier et al. 2009 (AGO-OVAR 2.3) Phase III (E) Topotecan Inferior OS
Sehouli et al. 2016 Phase III (C) PO Treosulfan Might have superior OS

Chemotherapy

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 verified protocol 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 PubMed

Vinorelbine monotherapy

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Regimen

Study Evidence
Rothenberg et al. 2004 Phase II

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. 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 protocol PubMed

Investigational agents

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