Difference between revisions of "Ovarian cancer"
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Revision as of 02:58, 31 January 2022
Section editor transclusions
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
This page contains regimens which were not tested in biomarker-specific or histology-specific populations.
The following links will take you to biomarker-specific subpages:
- Regimens for BRCA-mutated ovarian cancer are here.
The following links will take you to histology-specific subpages:
- Regimens for low-grade serous ovarian cancer (LGSOC) are here.
51 regimens on this page
98 variants on this page
|
Guidelines
ASCO
- 2020: Tew et al. PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline
ESMO
- 2016: Ledermann et al. eUpdate – Ovarian Cancer Treatment Recommendations
Older
- 2013: Ledermann et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
- 2012: Colombo et al. Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PubMed
ESMO/ESGO
- 2019: Colombo et al. ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease
NCCN
SGO/ASCO
- 2016: Wright et al. Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline
Adjuvant therapy for early stage disease
Carboplatin monotherapy
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Regimen variant #1, AUC 5
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Colombo et al. 2003 (ICON1) | 1991-2000 | Phase III (E-esc) | Observation | Superior OS1 |
1Reported efficacy is based on the 2003 pooled update.
Note: this is one of the recommended regimens for the experimental arm; other regimens were also used (see original paper).
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
21-day cycle for 6 cycles
Regimen variant #2, 350 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Trimbos et al. 2003 (ACTION) | 1990-2000 | Phase III (E-esc) | Observation | Superior OS1 |
1Reported efficacy is based on the 2003 pooled update.
Note: this is one of the recommended regimens for the experimental arm; other regimens were also used (see original paper). Cycle length was not specified in the paper; 21-day cycle is typical for this drug.
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) 350 mg/m2 IV once on day 1
21-day cycle for 4 to 6 cycles (see note)
References
- 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
- 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; EORTC Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst. 2003 Jan 15;95(2):105-12. link to original article PubMed
- ICON1: Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM, Torri V, Williams C, Lissoni A, Bonazzi C; ICON. International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst. 2003 Jan 15;95(2):125-32. link to original article PubMed NCT00002477
- 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; EORTC Collaborators-Adjuvant ChemoTherapy un Ovarian Neoplasm. International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst. 2003 Jan 15;95(2):105-12. link to original article PubMed
Carboplatin & Paclitaxel (CP)
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CP: Carboplatin & Paclitaxel
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bell et al. 2006 (GOG 157) | 1995-1998 | Phase III (C) | CP x 6 | Did not meet primary endpoint of RR |
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 7.5 IV over 30 minutes once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycle for 3 cycles
References
- 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
- 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 NCT00003644
Neoadjuvant chemotherapy for advanced stage disease
Carboplatin & Paclitaxel (CP)
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Regimen variant #1, AUC 5/175 x 3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kehoe et al. 2015 (CHORUS) | 2004-2010 | Phase III (E-switch-ic) | 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
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen variant #2, AUC 5/175 x 6
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Fagotti et al. 2016 (SCORPION) | 2011-2014 | Phase III (E-switch-ic) | Adjuvant Carboplatin & Paclitaxel | Did not meet primary endpoint of PFS | Superior QoL |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
Regimen variant #3, AUC 6/175 x 3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vergote et al. 2010 (EORTC 55971) | 1998-2006 | Phase III (E-switch-ic) | Adjuvant Carboplatin & Paclitaxel | Non-inferior OS |
Kehoe et al. 2015 (CHORUS) | 2004-2010 | Phase III (E-switch-ic) | 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
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- EORTC 55971: Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; EORTC-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. link to original article contains protocol in supplement PubMed NCT00003636
- 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 ISRCTN74802813
- 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 NCT01461850
First-line chemotherapy for advanced stage disease
Note: in a majority of these regimens, chemotherapy was preceded by primary debulking surgery.
Altretamine & Cisplatin
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wiernik et al. 1992a | 1979-1985 | Randomized (E-RT-de-esc) | Altretamine, Cisplatin, Pyridoxine | Not clearly reported |
Chemotherapy
References
- Wiernik PH, Yeap B, Vogl SE, Kaplan BH, Comis RL, Falkson G, Davis TE, Fazzini E, Cheuvart B, Horton J; ECOG. Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. Cancer Invest. 1992;10(1):1-9. link to original article PubMed
Carboplatin monotherapy
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Regimen variant #1, AUC 5
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Parmar et al. 1998 (ICON2) | 1991-1996 | Phase III (E-de-esc) | CAP | Did not meet primary endpoint of OS | Less toxic |
Parmar et al. 2002 (ICON3) | 1995-1998 | Phase III (C) | 1. CAP 2. Carboplatin & Paclitaxel |
Did not meet primary endpoint of OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
21-day cycle for 6 cycles
Regimen variant #2, AUC 6, q3wk
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Parmar et al. 2002 (ICON3) | 1995-1998 | Phase III (C) | 1. CAP 2. Carboplatin & Paclitaxel |
Did not meet primary endpoint of OS |
Banerjee et al. 2012 (SCOTROC 4) | 2004-2009 | Phase III (C) | Carboplatin; dose-escalated | Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
21-day cycle for 6 cycles
Regimen variant #3, AUC 6, q4wk
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gore et al. 1998 | 1987-1995 | Phase III (C) | Carboplatin; AUC 12 x 4 | Did not meet primary endpoint of OS24 |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
28-day cycle for 6 cycles
Regimen variant #4, AUC 9
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Markman et al. 2001 (GOG 114) | 1992-1995 | Phase III (E-esc) | See link | See link |
Preceding treatment
- Primary debulking surgery, with optimal debulking
Chemotherapy
- Carboplatin (Paraplatin) AUC 9 IV once on day 1
28-day cycle for 2 cycles
Subsequent treatment
Regimen variant #5, 400 mg/m2, q4wk
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Taylor et al. 1994b | 1981-1984 | Phase III (C) | Cisplatin | Did not meet primary endpoint of ORR |
Mangioni et al. 1989 | 1985-1987 | Phase III (C) | Cisplatin | Did not meet endpoint |
Of historic interest.
Chemotherapy
- Carboplatin (Paraplatin) 400 mg/m2 IV once on day 1
28-day cycle for 10 cycles
References
- 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
- 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
- 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
- ICON2: Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C; ICON. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer: International Collaborative Ovarian Neoplasm Study. Lancet. 1998 Nov 14;352(9140):1571-6. link to original article contains verified protocol PubMed
- 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
- 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
- SCOTROC 4: Banerjee S, Rustin G, Paul J, Williams C, Pledge S, Gabra H, Skailes G, Lamont A, Hindley A, Goss G, Gilby E, Hogg M, Harper P, Kipps E, Lewsley LA, Hall M, Vasey P, Kaye SB; GCIG. A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG. Ann Oncol. 2013 Mar;24(3):679-87. Epub 2012 Oct 5. link to original article link to PMC article contains protocol PubMed NCT00098878
Carboplatin & Docetaxel
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vasey et al. 2004 (SCOTROC-1) | 1998-2000 | Phase III (E-switch-ic) | Carboplatin & Paclitaxel | Did not meet primary endpoint of PFS |
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1, given first
Supportive medications
- Dexamethasone (Decadron) 8 mg PO twice per day the day before, the day of, and day after Docetaxel (Taxotere)
- ONE of the following 5-HT3 antagonists:
- Ondansetron (Zofran) 8 mg
- Granisetron 3 mg
21-day cycle for 6 cycles
References
- SCOTROC-1: Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. link to original article contains verified protocol PubMed NCT00003998
Carboplatin & Doxorubicin liposomal
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pignata et al. 2006 (MITO-2) | 2003-2007 | Phase III (E-switch-ic) | Carboplatin & Paclitaxel | Did not meet primary endpoint of PFS |
Eligibility criteria for MITO-2 included: "a cytologic or histologic diagnosis of epithelial ovarian cancer (stage IC to IV according to International Federation of Gynecology and Obstetrics staging system).
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given first
- Pegylated liposomal doxorubicin (Doxil) 30 mg/m2 IV over 60 minutes once on day 1, given second
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
- MITO-2: Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. link to original article contains verified protocol link to PMC article PubMed NCT00326456
- 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 (GCb)
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gordon et al. 2011 | 2002-2006 | Phase III (E-switch-ic) | Carboplatin & Paclitaxel | Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
21-day cycle for up to 6 cycles
Subsequent treatment
- Patients with CR could optionally receive paclitaxel consolidation
References
- 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 (CP)
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TC: Taxol (Paclitaxel) & Carboplatin
PC: Paclitaxel & Carboplatin
Regimen variant #1, q1wk AUC 2/60
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pignata et al. 2014 (MITO-7) | 2008-2012 | Phase III (E-switch-ic) | TC; q3wk AUC 6/175 | Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15
- Paclitaxel (Taxol) 60 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 6 cycles
Regimen variant #2, q3wk AUC 5, q1wk 80
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Monk et al. 2021 (JAVELIN Ovarian 100) | 2016-2018 | Phase III (C) | 1. CP & Avelumab 2. CP, then Avelumab |
Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 6 cycles
Regimen variant #3, q3wk AUC 5/175
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Neijt et al. 2000 | 1994-1997 | Phase III (E-switch-ic) | Cisplatin & Paclitaxel | Did not meet primary endpoint of PFS | |
du Bois et al. 2006 (AGO-OVAR 5) | 1997-2000 | Phase III (C) | TEC | Did not meet primary endpoint of OS | |
Vasey et al. 2004 (SCOTROC-1) | 1998-2000 | Phase III (C) | Carboplatin & Docetaxel | Did not meet primary endpoint of PFS | |
Möbus et al. 2007 (HIDOC-EIS) | 1998-2004 | Phase III (C) | High-dose chemotherapy with auto HSCT | Did not meet primary endpoint of PFS | |
Lindemann et al. 2012 (EORTC 55981) | 1999-2001 | Phase III (C) | TEC | Did not meet primary endpoint of PFS | |
Hoskins et al. 2010 (EORTC 55012) | 2001-2005 | Phase III (C) | Cisplatin & Topotecan, then TC | Did not meet primary endpoint of PFS | Less toxic |
du Bois et al. 2010 (AGO-OVAR 9) | 2002-2004 | Phase III (C) | TCG | Did not meet primary endpoint of OS | |
Pignata et al. 2006 (MITO-2) | 2003-2007 | Phase III (C) | Carboplatin & Pegylated liposomal doxorubicin | Did not meet primary endpoint of PFS | |
du Bois et al. 2015 (AGO-OVAR 12) | 2009-2011 | Phase III (C) | TC & Nintedanib | Seems to have inferior PFS | |
Fagotti et al. 2016 (SCORPION) | 2011-2014 | Phase III (C) | TC; neoadjuvant | Did not meet primary endpoint of PFS | Inferior QoL |
Clamp et al. 2019 (ICON8) | 2011-2014 | Phase III (C) | 1. TC; q1wk AUC 2/80 2. TC; q3wk AUC 6, q1wk 80 ("dose-dense") |
Did not meet primary endpoints of PFS/OS | |
Vergote et al. 2019 (TRINOVA-3) | 2012-2014 | Phase III (C) | TC & Trebananib | Did not meet primary endpoint of PFS | |
Monk et al. 2021 (JAVELIN Ovarian 100) | 2016-2018 | Phase III (C) | 1. CP & Avelumab 2. CP, then Avelumab |
Did not meet primary endpoint of PFS |
Note: In MITO-2, all patients received 3 cycles of therapy. Patients with stable or responsive disease received an additional 3 cycles.
Preceding treatment
- Neijt et al. 2000: Primary debulking surgery was recommended
- SCOTROC-1, MITO-2, AGO-OVAR 12, SCORPION: Primary debulking surgery
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
- MITO-2 gave carboplatin over 30 minutes
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
Supportive medications
- (per Vasey et al. 2004):
- Dexamethasone (Decadron) 20 mg PO given twice on day 1; 12 and 6 hours prior to Paclitaxel (Taxol)
- One of the following antihistamines:
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Chlorpheniramine (Chlor-Trimeton) 10 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- One of the following H2-blockers
- Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- One of the following serotonin 5-HT3 antagonists:
- Ondansetron (Zofran) 8 mg
- Granisetron 3 mg
21-day cycle for 6 or more cycles (see note)
Regimen variant #4, q3wk AUC 6, q1wk 80
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Katsumata et al. 2009 (JGOG 3016) | 2003-2005 | Phase III (E-switch-ic) | TC; q3wk AUC 6/180 | Seems to have superior OS |
Coleman et al. 2019 (VELIA) | 2015-2017 | Phase III (C) | CP & Veliparib x 6 | Not reported |
CP & Veliparib x 6, then Veliparib maint. | Inferior PFS | |||
Monk et al. 2021 (JAVELIN Ovarian 100) | 2016-2018 | Phase III (C) | 1. CP & Avelumab 2. CP, then Avelumab |
Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
Supportive medications
- "Standard premedication"
21-day cycle for 6 to 9 cycles, depending on response and protocol
Regimen variant #5, q3wk AUC 6/175
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lhommé et al. 2008 | 1997-1999 | Phase III (C) | Paclitaxel & Valspodar | Did not meet primary endpoint of TTP |
Vergote et al. 2010 (EORTC 55971) | 1998-2006 | Phase III (C) | TC x 3, then interval debulking, then TC x 3 | Non-inferior OS |
Gordon et al. 2011 | 2002-2006 | Phase III (C) | Carboplatin & Gemcitabine | Did not meet primary endpoint of PFS |
Bookman et al. 2009 (ICON5) | 2001-2004 | Phase III (C) | 1. TCG 2. TC & PLD 3. TC & Topotecan |
Did not meet primary endpoint of OS |
Alberts et al. 2008 (GRACES) | 2002-2004 | Phase III (C) | CP & IFN gamma-1b | Did not meet primary endpoint of OS |
Burger et al. 2011 (GOG-0218) | 2005-2009 | Phase III (C) | 1. TC & Bevacizumab x 6 | Did not meet primary endpoint of PFS |
2. TC & Bevacizumab x 6, then Bev maintenance | Inferior PFS | |||
Perren et al. 2011 (ICON7) | 2006-2009 | Phase III (C) | Carboplatin, Paclitaxel, Bevacizumab | Did not meet primary endpoints of PFS/OS1 |
Sugiyama et al. 2016 (JGOG3017/GCIG) | 2006-2011 | Phase III (C) | Cisplatin & Irinotecan | Did not meet primary endpoint of PFS |
Pignata et al. 2014 (MITO-7) | 2008-2012 | Phase III (C) | TC; q1wk AUC 2/60 | Did not meet primary endpoint of PFS |
du Bois et al. 2015 (AGO-OVAR 12) | 2009-2011 | Phase III (C) | TC & Nintedanib | Seems to have inferior PFS |
Chan et al. 2016 (GOG-0262) | 2010-2012 | Phase III (C) | TC; dose-dense | Did not meet primary endpoint of PFS |
Clamp et al. 2019 (ICON8) | 2011-2014 | Phase III (C) | 1. TC; q1wk AUC 2/80 2. TC; q3wk AUC 6, q1wk 80 ("dose-dense") |
Did not meet primary endpoints of PFS/OS |
Vergote et al. 2019 (TRINOVA-3) | 2012-2014 | Phase III (C) | TC & Trebananib | Did not meet primary endpoint of PFS |
Coleman et al. 2019 (VELIA) | 2015-2017 | Phase III (C) | TC & Veliparib x 6 | Not reported |
TC & Veliparib x 6, then Veliparib maint. | Inferior PFS | |||
Monk et al. 2021 (JAVELIN Ovarian 100) | 2016-2018 | Phase III (C) | 1. CP & Avelumab 2. CP, then Avelumab |
Did not meet primary endpoint of PFS |
1Reported efficacy for ICON7 is based on the 2015 update.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycle for up to 6 to 8 cycles
Subsequent treatment
- Gordon et al. 2011: Patients with CR could optionally proceed to receive paclitaxel consolidation
Regimen variant #6, q3wk AUC 6/180
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Katsumata et al. 2009 (JGOG 3016) | 2003-2005 | Phase III (C) | TC; dose-dense | Seems to have inferior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1
- Paclitaxel (Taxol) 180 mg/m2 IV over 3 hours once on day 1
Supportive medications
- "Standard premedication"
21-day cycle for 6 to 9 cycles, depending on response
Regimen variant #7, AUC 6/185
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
du Bois et al. 2003 (AGO-OVAR 3) | 1995-1997 | Phase III (C) | Cisplatin & Paclitaxel | Non-inferior PFS | Superior QoL |
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 30 to 60 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
Regimen variant #8, q3wk AUC 7/175
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Aravantinos et al. 2005 | 1995-1999 | Phase III (C) | CP/Cisplatin & Paclitaxel | Did not meet primary endpoint of OS |
Aravantinos et al. 2008 | 1999-2004 | Phase III (C) | Cisplatin, Doxorubicin, Paclitaxel | Might have inferior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 7 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycle for 6 cycles
Regimen variant #9, q3wk AUC 7.5/175
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ozols et al. 2003 (GOG 158) | NR | Phase III (E-switch-ic) | Cisplatin & Paclitaxel | Seems to have non-inferior RFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 7.5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- Dexamethasone (Decadron) with one of the following options:
- 20 mg PO twice on day 1; 12 and 6 hours prior to chemotherapy
- 20 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
21-day cycle for 6 cycles
References
- 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
- 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
- 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
- SCOTROC-1: Vasey PA, Jayson GC, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye SB; Scottish Gynaecological Cancer Trials Group. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004 Nov 17;96(22):1682-91. link to original article contains verified protocol PubMed NCT00003998
- 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
- 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
- HIDOC-EIS: Möbus V, Wandt H, Frickhofen N, Bengala C, Champion K, Kimmig R, Ostermann H, Hinke A, Ledermann JA; AGO-OVAR; AIO; EBMT. Phase III trial of high-dose sequential chemotherapy with peripheral blood stem cell support compared with standard dose chemotherapy for first-line treatment of advanced ovarian cancer: intergroup trial of the AGO-Ovar/AIO and EBMT. J Clin Oncol. 2007 Sep 20;25(27):4187-93. Epub 2007 Aug 13. link to original article contains verified protocol PubMed NCT00004921
- MITO-2: Pignata S, Scambia G, Savarese A, Breda E, Scollo P, De Vivo R, Rossi E, Gebbia V, Natale D, Del Gaizo F, Naglieri E, Ferro A, Musso P, D'Arco AM, Sorio R, Pisano C, Di Maio M, Signoriello G, Annunziata A, Perrone F; MITO. Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial. BMC Cancer. 2006 Aug 1;6:202. link to original article contains verified protocol link to PMC article PubMed NCT00326456
- 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
- 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
- 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
- Aravantinos G, Fountzilas G, Bamias A, Grimani I, Rizos S, Kalofonos HP, Skarlos DV, Economopoulos T, Kosmidis PA, Stathopoulos GP, Briasoulis E, Pectasides D, Samantas E, Timotheadou E, Papadimitriou C, Papanikolaou A, Onyenadum A, Papakostas P, Bafaloukos D, Dimopoulos MA; Hellenic Cooperative Oncology Group. Carboplatin and paclitaxel versus cisplatin, paclitaxel and doxorubicin for first-line chemotherapy of advanced ovarian cancer: a Hellenic Cooperative Oncology Group (HeCOG) study. Eur J Cancer. 2008 Oct;44(15):2169-77. Epub 2008 Aug 6. link to original article contains protocol PubMed
- ICON5: Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, Colombo N, Fowler JM, Argenta PA, De Geest K, Mutch DG, Burger RA, Swart AM, Trimble EL, Accario-Winslow C, Roth LM; Gynecologic Cancer Intergroup. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a phase III trial of the Gynecologic Cancer Intergroup. J Clin Oncol. 2009 Mar 20;27(9):1419-25. Epub 2009 Feb 17. Erratum in: J Clin Oncol. 2009 May 1;27(13):2305. link to original article link to PMC article contains verified protocol PubMed NCT00011986
- 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 NCT00226915
- 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
- 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 NCT00052468
- EORTC 55971: Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; EORTC-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. link to original article contains protocol in supplement PubMed NCT00003636
- EORTC 55012: Hoskins P, Vergote I, Cervantes A, Tu D, Stuart G, Zola P, Poveda A, Provencher D, Katsaros D, Ojeda B, Ghatage P, Grimshaw R, Casado A, Elit L, Mendiola C, Sugimoto A, D'Hondt V, Oza A, Germa JR, Roy M, Brotto L, Chen D, Eisenhauer EA. Advanced ovarian cancer: phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel. J Natl Cancer Inst. 2010 Oct 20;102(20):1547-56. Epub 2010 Oct 11. link to original article contains protocol PubMed NCT00028743
- 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
- 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 NCT00262847
- Update: Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. Epub 2019 Jun 19. link to original article link to PMC article PubMed
- ICON7: Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. link to original article contains verified protocol PubMed NCT00483782
- Update: Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Park-Simon TW, Rustin G, Joly F, Mirza MR, Plante M, Quinn M, Poveda A, Jayson GC, Stark D, Swart AM, Farrelly L, Kaplan R, Parmar MK, Perren TJ; ICON. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):928-36. Epub 2015 Jun 23. link to original article link to PMC article PubMed
- EORTC 55981: Lindemann K, Christensen RD, Vergote I, Stuart G, Izquierdo MA, Kærn J, Havsteen H, Eisenhauer E, Ridderheim M, Lopez AB, Hirte H, Aavall-Lundquvist E, Vrdoljak E, Green J, Kristensen GB; Gynecologic Cancer Intergroup. First-line treatment of advanced ovarian cancer with paclitaxel/carboplatin with or without epirubicin (TEC versus TC)--a Gynecologic Cancer Intergroup study of the NSGO, EORTC GCG and NCIC-CTG. Ann Oncol. 2012 Oct;23(10):2613-9. Epub 2012 Apr 26. link to original article contains protocol PubMed NCT00004934
- MITO-7: Pignata S, Scambia G, Katsaros D, Gallo C, Pujade-Lauraine E, De Placido S, Bologna A, Weber B, Raspagliesi F, Panici PB, Cormio G, Sorio R, Cavazzini MG, Ferrandina G, Breda E, Murgia V, Sacco C, Cinieri S, Salutari V, Ricci C, Pisano C, Greggi S, Lauria R, Lorusso D, Marchetti C, Selvaggi L, Signoriello S, Piccirillo MC, Di Maio M, Perrone F; MITO; GINECO; Mario Negri Gynecologic Oncology (MaNGO); European Network of Gynaecological Oncological Trial Groups; Gynecologic Cancer InterGroup. Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2014 Apr;15(4):396-405. Epub 2014 Feb 28. link to original article PubMed NCT00660842
- 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 ISRCTN74802813
- 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 NCT01015118
- Update: Ray-Coquard I, Cibula D, Mirza MR, Reuss A, Ricci C, Colombo N, Koch H, Goffin F, González-Martin A, Ottevanger PB, Baumann K, Bjørge L, Lesoin A, Burges A, Rosenberg P, Gropp-Meier M, Harrela M, Harter P, Frenel JS, Minarik T, Pisano C, Hasenburg A, Merger M, du Bois A; AGO Study Group-led GCIG/ENGOT Intergroup Consortium. Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer. Int J Cancer. 2020 Jan 15;146(2):439-448. Epub 2019 Sep 6. link to original article PubMed
- 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 NCT01167712
- 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 NCT01461850
- 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 UMIN000000499
- 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 NCT01493505
- VELIA: Coleman RL, Fleming GF, Brady MF, Swisher EM, Steffensen KD, Friedlander M, Okamoto A, Moore KN, Efrat Ben-Baruch N, Werner TL, Cloven NG, Oaknin A, DiSilvestro PA, Morgan MA, Nam JH, Leath CA 3rd, Nicum S, Hagemann AR, Littell RD, Cella D, Baron-Hay S, Garcia-Donas J, Mizuno M, Bell-McGuinn K, Sullivan DM, Bach BA, Bhattacharya S, Ratajczak CK, Ansell PJ, Dinh MH, Aghajanian C, Bookman MA. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2403-2415. Epub 2019 Sep 28. link to original article link to PMC article PubMed NCT02470585
- ICON8: Clamp AR, James EC, McNeish IA, Dean A, Kim JW, O'Donnell DM, Hook J, Coyle C, Blagden S, Brenton JD, Naik R, Perren T, Sundar S, Cook AD, Gopalakrishnan GS, Gabra H, Lord R, Dark G, Earl HM, Hall M, Banerjee S, Glasspool RM, Jones R, Williams S, Swart AM, Stenning S, Parmar M, Kaplan R, Ledermann JA. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial. Lancet. 2019 Dec 7;394(10214):2084-2095. Epub 2019 Nov 29. link to original article contains protocol link to PMC article PubMed NCT01654146
- JAVELIN Ovarian 100: Monk BJ, Colombo N, Oza AM, Fujiwara K, Birrer MJ, Randall L, Poddubskaya EV, Scambia G, Shparyk YV, Lim MC, Bhoola SM, Sohn J, Yonemori K, Stewart RA, Zhang X, Perkins Smith J, Linn C, Ledermann JA. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Aug 4:S1470-2045(21)00342-9. Epub ahead of print. link to original article contains protocol PubMed NCT02718417
- FLORA-5: NCT04498117
- KEYLYNK-001: NCT03740165
Carboplatin & Paclitaxel (CP) & Bevacizumab
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TC-BEV: Taxol (Paclitaxel), Carboplatin, BEVacizumab
Regimen variant #1, q3wk paclitaxel, standard-dose bevacizumab
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burger et al. 2011 (GOG-0218) | 2005-2009 | Phase III (E-RT-esc) | Carboplatin & Paclitaxel | Superior PFS1 |
Chan et al. 2016 (GOG-0262) | 2010-2012 | Phase III (C) | TC-Bev; dose-dense | Did not meet primary endpoint of PFS |
Moore et al. 2021 (IMagyn050) | 2017-2019 | Phase III (C) | Carboplatin & Paclitaxel (CP), Atezolizumab, Bevacizumab | Did not meet primary endpoint of PFS |
1Superior efficacy in GOG-0218 was only demonstrated in the arm that went on to receive bevacizumab maintenance.
Note: Decision to use bevacizumab in GOG-0262 was at the discretion of the patient; it was not a randomization.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Targeted therapy
- Bevacizumab (Avastin) as follows:
- Cycles 2 to 6: 15 mg/kg IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
- GOG-0218: No further treatment versus bevacizumab maintenance
- GOG-0262 & IMagyn050: Bevacizumab maintenance
Regimen variant #2, q3wk paclitaxel, low-dose bevacizumab
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Perren et al. 2011 (ICON7) | 2006-2009 | Phase III (E-esc) | Carboplatin & Paclitaxel | Did not meet primary endpoints of PFS/OS1 |
1Reported efficacy is based on the 2015 update.
Note: Bevacizumab is not given with cycle 1 if chemotherapy starts within 4 weeks of surgery.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 to 6 IV over 30 to 60 minutes once on day 1
- The protocol linked from Perren et al. 2011 clarifies that the recommended dose was AUC 6, but that it could be adjusted per standard practice
- Cycles 1 to 6: AUC 5 to 6 IV over 30 to 60 minutes once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m2 IV over 3 hours once on day 1
Targeted therapy
- Bevacizumab (Avastin) as follows:
- Cycles 1 to 6: 7.5 mg/kg IV once on day 1
- Cycles 7 to 18: 15 mg/kg IV once on day 1
21-day cycle for 18 cycles
Regimen variant #3, weekly paclitaxel
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Walker et al. 2019 (GOG-252) | 2009-2011 | Phase III (C) | 1. IP Carboplatin, IV Paclitaxel, Bevacizumab 2. IP Cisplatin, IV/IP Paclitaxel, Bevacizumab |
Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Bevacizumab (Avastin) as follows:
- Cycles 2 to 6: 15 mg/kg IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
References
- 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 NCT00262847
- Update: Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. Epub 2019 Jun 19. link to original article link to PMC article PubMed
- ICON7: Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. link to original article contains verified protocol PubMed NCT00483782
- Update: Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Park-Simon TW, Rustin G, Joly F, Mirza MR, Plante M, Quinn M, Poveda A, Jayson GC, Stark D, Swart AM, Farrelly L, Kaplan R, Parmar MK, Perren TJ; ICON. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):928-36. Epub 2015 Jun 23. link to original article link to PMC article PubMed
- 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 NCT01167712
- 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 NCT00951496
- IMagyn050: Moore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, Myers T, Taskiran C, Robison K, Mäenpää J, Willmott L, Colombo N, Thomes-Pepin J, Liontos M, Gold MA, Garcia Y, Sharma SK, Darus CJ, Aghajanian C, Okamoto A, Wu X, Safin R, Wu F, Molinero L, Maiya V, Khor VK, Lin YG, Pignata S. Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol. 2021 Jun 10;39(17):1842-1855. Epub 2021 Apr 23. link to original article contains verified protocol link to PMC article PubMed NCT03038100
- FIRST: NCT03602859
Cisplatin & Paclitaxel
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TP: Taxol (Paclitaxel) & Platinol (Cisplatin)
PT: Platinol (Cisplatin) & Taxol (Paclitaxel)
Regimen variant #1, 75/135
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McGuire et al. 1996 (GOG 111) | NR | Phase III (E-RT-switch-ic) | Cisplatin & Cyclophosphamide | Superior OS |
Muggia et al. 2000 (GOG 132) | 1992-1994 | Phase III (C) | 1. Cisplatin 2. Paclitaxel |
Did not meet primary endpoint of PFS |
Markman et al. 2001 (GOG 114) | 1992-1995 | Phase III (C) | Carboplatin, then IP Cisplatin & IV Paclitaxel | Seems to have inferior OS |
Ozols et al. 2003 (GOG 158) | NR | Phase III (C) | Carboplatin & Paclitaxel | Seems to have non-inferior RFS |
Rose et al. 2004 (GOG 152) | 1994-2001 | Phase III (C) | Cisplatin & Paclitaxel; with interval debulking | Did not meet primary endpoint of OS |
Armstrong et al. 2006 (GOG 172) | 1998-2001 | Phase III (C) | Cisplatin & Paclitaxel; IP | Seems to have inferior OS |
Spriggs et al. 2007 (GOG 162) | NR | Phase III (C) | Cisplatin & Paclitaxel; prolonged-infusion paclitaxel | Did not meet primary endpoint of OS |
Preceding treatment
- GOG 111, 132, 152: Primary debulking surgery, with suboptimal debulking
- GOG 114, 158, 172: Primary debulking surgery, with optimal debulking
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Some regimens give the cisplatin after the paclitaxel (i.e., on day 2)
- Paclitaxel (Taxol) 135 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive medications
- (details vary depending on reference):
- Dexamethasone (Decadron) with one of the following options:
- 20 mg PO twice on day 1; 12 and 6 hours prior to chemotherapy
- 20 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- "Hydration and antiemetic agents" once on day 1, prior to Cisplatin (Platinol)
21-day cycle for 6 cycles
Regimen variant #2, 75/175
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Piccart et al. 2000 (OV10) | NR-1995 | Phase III (E-RT-switch-ic) | Cisplatin & Cyclophosphamide | Superior OS |
Neijt et al. 2000 | 1994-1997 | Phase III (C) | Carboplatin & Paclitaxel | Did not meet primary endpoint of PFS |
Mouratidou et al. 2007 | 1998-2002 | Phase III (E-switch-ic) | Cisplatin & Cyclophosphamide | Did not meet primary endpoint of PFS |
van der Burg et al. 2014 | 1999-2006 | Phase III (C) | Cisplatin & Paclitaxel; weekly paclitaxel | Did not meet primary endpoint of PFS |
Preceding treatment
- OV10: Primary debulking surgery, with optimal or suboptimal debulking
- Neijt et al. 2000: Primary debulking surgery was recommended
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1, given second
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
21-day cycle for 6 or more cycles
Regimen variant #3, 75/185
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
du Bois et al. 2003 (AGO-OVAR 3) | 1995-1997 | 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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 NCT00002568
- 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 NCT00003322
- 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
- 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
- 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 NCT00002717
- 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
TC & Nintedanib
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TC & Nintedanib: Taxol (Paclitaxel), Carboplatin, Nintedanib
Regimen variant #1, q3wk AUC 5/175
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
du Bois et al. 2015 (AGO-OVAR 12) | 2009-2011 | Phase III (E-esc) | TC | Seems to have superior PFS Median PFS: 17.2 vs 16.6 mo (HR 0.84, 95% CI 0.72-0.98) |
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
Targeted therapy
- Nintedanib (Vargatef) 200 mg PO twice per day on days 2 to 21
21-day cycles
Regimen variant #2, q3wk AUC 6/175
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
du Bois et al. 2015 (AGO-OVAR 12) | 2009-2011 | Phase III (E-esc) | TC | Seems to have superior PFS Median PFS: 17.2 vs 16.6 mo (HR 0.84, 95% CI 0.72-0.98) |
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1, given second
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
Targeted therapy
- Nintedanib (Vargatef) 200 mg PO twice per day on days 2 to 21
21-day cycles
References
- 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 NCT01015118
- Update: Ray-Coquard I, Cibula D, Mirza MR, Reuss A, Ricci C, Colombo N, Koch H, Goffin F, González-Martin A, Ottevanger PB, Baumann K, Bjørge L, Lesoin A, Burges A, Rosenberg P, Gropp-Meier M, Harrela M, Harter P, Frenel JS, Minarik T, Pisano C, Hasenburg A, Merger M, du Bois A; AGO Study Group-led GCIG/ENGOT Intergroup Consortium. Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer. Int J Cancer. 2020 Jan 15;146(2):439-448. Epub 2019 Sep 6. link to original article PubMed
Intraperitoneal therapy
Cisplatin & Paclitaxel
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Regimen variant #1, IV paclitaxel
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Markman et al. 2001 (GOG 114) | 1992-1995 | Phase III (E-switch-ic) | See link | See link |
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IP once on day 2
- Paclitaxel (Taxol) 135 mg/m2 IV continuous infusion over 24 hours, started on day 1
21-day cycle for 6 cycles
Regimen variant #2, IV/IP paclitaxel
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Armstrong et al. 2006 (GOG 172) | 1998-2001 | Phase III (E-switch-ic) | Cisplatin & Paclitaxel; IV | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IP rapid infusion once on day 2
- Walker et al. 2006 instructs that the patient be rolled onto 4 different positions every 15 minutes to evenly distribute cisplatin
- Paclitaxel (Taxol) 135 mg/m2 IV continuous infusion over 24 hours, started on day 1, then 60 mg/m2 IP rapid infusion once on day 8
Supportive 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
- 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
- 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 NCT00003322
- 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 | Years of enrollment | Evidence |
---|---|---|
Rothenberg et al. 2001 (SWOG-9326) | 1993-1997 | Phase II |
Chemotherapy
- Altretamine (Hexalen) 260 mg/m2/day PO on days 1 to 14, split into 4 daily doses
28-day cycle for 6 cycles
References
- SWOG-9326: Rothenberg ML, Liu PY, Wilczynski S, Hannigan EV, Weiner SA, Weiss GR, Hunter VJ, Chapman JA, Tiersten A, Kohler PC, Alberts DS. Phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer: a Southwest Oncology Group trial (SWOG-9326). Gynecol Oncol. 2001 Aug;82(2):317-22. link to original article contains protocol PubMed
- Update: Alberts DS, Jiang C, Liu PY, Wilczynski S, Markman M, Rothenberg ML. Long-term follow-up of a phase II trial of oral altretamine for consolidation of clinical complete remission in women with stage III epithelial ovarian cancer in the Southwest Oncology Group. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):224-8. link to original article PubMed
Bevacizumab monotherapy
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Regimen variant #1, 16 cycles
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burger et al. 2011 (GOG-0218) | 2005-2009 | Non-randomized portion of RCT | ||
Walker et al. 2019 (GOG-252) | 2009-2011 | Non-randomized portion of RCT | ||
Awaiting publication (BOOST) | 2011-2013 | Phase 3 (C) | Bevacizumab x 30 mo | Did not meet primary endpoint of PFS |
Ray-Coquard et al. 2019 (PAOLA-1) | 2015-2017 | Phase 3 (C) | Olaparib & Bevacizumab | Inferior PFS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of treatment is 22 cycles (including the 6 cycles of combination chemotherapy).
Preceding treatment
- GOG-0218 & BOOST: Carboplatin, Paclitaxel, Bevacizumab x 6
- GOG-252: Carboplatin, Paclitaxel, Bevacizumab x 6 versus IP Carboplatin, IV Paclitaxel, Bevacizumab x 6 versus IP Cisplatin, IV/IP Paclitaxel, Bevacizumab x 6
- PAOLA-1: Not specified, but presumably platinum doublet & bevacizumab x 6
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 16 cycles
Regimen variant #2, indefinite
Study | Years of enrollment | Evidence |
---|---|---|
Chan et al. 2016 (GOG-0262) | 2010-2012 | 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
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- 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 NCT00262847
- Update: Tewari KS, Burger RA, Enserro D, Norquist BM, Swisher EM, Brady MF, Bookman MA, Fleming GF, Huang H, Homesley HD, Fowler JM, Greer BE, Boente M, Liang SX, Ye C, Bais C, Randall LM, Chan JK, Ferriss JS, Coleman RL, Aghajanian C, Herzog TJ, DiSaia PJ, Copeland LJ, Mannel RS, Birrer MJ, Monk BJ. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol. 2019 Sep 10;37(26):2317-2328. Epub 2019 Jun 19. link to original article link to PMC article PubMed
- 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 NCT01167712
- 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 NCT00951496
- PAOLA-1: Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. link to original article contains verified protocol PubMed NCT02477644
- BOOST: NCT01462890
Niraparib monotherapy
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Regimen variant #1, 200 mg/day
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
González-Martín et al. 2019 (PRIMA) | 2016-2018 | Phase III (E-RT-esc) | Placebo | Superior PFS1 Median PFS: 13.8 vs 8.2 mo (HR 0.62, 95% CI 0.50-0.76) |
1Reported efficacy is for the overall population.
Note: this dose was used for patients with body weight of less than 77 kg or a platelet count of less than 150 x 109/L.
Preceding treatment
- Platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
Targeted therapy
- Niraparib (Zejula) 200 mg PO once per day
28-day cycle for up to 39 cycles (3 years)
Regimen variant #2, 300 mg/day
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
González-Martín et al. 2019 (PRIMA) | 2016-2018 | Phase III (E-RT-esc) | Placebo | Superior PFS1 Median PFS: 13.8 vs 8.2 mo (HR 0.62, 95% CI 0.50-0.76) |
1Reported efficacy is for the overall population.
Preceding treatment
- Platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
Targeted therapy
- Niraparib (Zejula) 300 mg PO once per day
28-day cycle for up to 39 cycles (3 years)
References
- PRIMA: González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. Epub 2019 Sep 28. link to original article PubMed NCT02655016
Olaparib & Bevacizumab
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ray-Coquard et al. 2019 (PAOLA-1) | 2015-2017 | Phase 3 (E-RT-esc) | Bevacizumab | Superior PFS Median PFS: 22.1 vs 16.6 mo (HR 0.59, 95% CI 0.49-0.72) |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The FDA-recommended duration of bevacizumab treatment is 22 cycles (including the 6 cycles of combination chemotherapy).
Preceding treatment
- Not specified, but presumably platinum doublet & bevacizumab x 6; olaparib is started between 3 and 9 weeks after last chemotherapy dose.
Targeted therapy
- Olaparib (Lynparza) 300 mg PO twice per day
- Bevacizumab (Avastin) as follows:
- Cycles 1 to 16: 15 mg/kg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- PAOLA-1: Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. link to original article contains verified protocol PubMed NCT02477644
Paclitaxel monotherapy
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Regimen variant #1, 135 mg/m2 q4wk
Study | Years of enrollment | Evidence |
---|---|---|
Gordon et al. 2011 | 2002-2006 | Non-randomized portion of RCT |
Preceding treatment
- Carboplatin & Gemcitabine x 6 versus Carboplatin & Paclitaxel x 6
Chemotherapy
- Paclitaxel (Taxol) 135 mg/m2 IV once on day 1
28-day cycle for up to 12 cycles
Regimen variant #2, 175 mg/m2 q3wk x 3
Study | Years of enrollment | Evidence |
---|---|---|
Micha et al. 2005 | NR in abstract | Phase II, <20 patients in this subgroup |
Preceding treatment
- Carboplatin, Gemcitabine, Paclitaxel x 6
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 3 cycles
Regimen variant #3, 175 mg/m2 q3wk x 12
Study | Years of enrollment | Evidence |
---|---|---|
Micha et al. 2005 | NR in abstract | Phase II, <20 patients in this subgroup |
Preceding treatment
- Carboplatin, Gemcitabine, Paclitaxel x 6
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 12 cycles
Regimen variant #4, 175 mg/m2 q4wk x 3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Markman et al. 2003 (GOG 178) | 1997-2001 | Phase III (C) | Paclitaxel x 12 | Inferior PFS |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
28-day cycle for 3 cycles
Regimen variant #5, 175 mg/m2 q4wk x 12
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Markman et al. 2003 (GOG 178) | 1997-2001 | Phase III (E-esc) | Paclitaxel x 3 | Superior PFS |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
28-day cycle for 12 cycles
References
- GOG 178: Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D; SWOG; Gynecologic Oncology Group. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol. 2003 Jul 1;21(13):2460-5. link to original article contains verified protocol PubMed NCT00003120
- 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
- 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
- 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
- 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Du Bois et al. 2014 (AGO-OVAR 16) | 2009-2010 | Phase III (E-esc) | Placebo | Superior PFS Median PFS: 17.9 vs 12.3 mo (HR 0.77, 95% CI 0.64-0.91) |
Patients enrolled in AGO-OVAR 16 had histologically confirmed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, were FIGO II to IV, and no evidence of progression after initial treatment.
Preceding treatment
- Surgery and at least 5 cycles of platinum and taxane combination chemotherapy
Targeted therapy
- Pazopanib (Votrient) 800 mg PO once per day
24-month course
References
- 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 NCT00866697
- Subgroup analysis: Kim JW, Mahner S, Wu LY, Shoji T, Kim BG, Zhu JQ, Takano T, Park SY, Kong BH, Wu Q, Wang KL, Ngan HY, Liu JH, Wei LH, Mitrica I, Zhang P, Crescenzo R, Wang Q, Cox CJ, Harter P, du Bois A. Pazopanib maintenance therapy in East Asian women with advanced epithelial ovarian cancer: results from AGO-OVAR16 and an East Asian Study. Int J Gynecol Cancer. 2018 Jan;28(1):2-10. link to original article PubMed
- Update: Vergote I, du Bois A, Floquet A, Rau J, Kim JW, Del Campo JM, Friedlander M, Pignata S, Fujiwara K, Colombo N, Mirza MR, Monk BJ, Tsibulak I, Calvert PM, Herzog TJ, Hanker LC, Meunier J, Lee JY, Bologna A, Carrasco-Alfonso MJ, Harter P. Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer. Gynecol Oncol. 2019 Nov;155(2):186-191. Epub 2019 Sep 10. link to original article PubMed
Second-line therapy for relapsed or recurrent disease, platinum-sensitive
Carboplatin monotherapy
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Regimen variant #1, AUC 5
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Parmar et al. 2003 (ICON4) | 1996-2002 | Phase III (C) | 1. Carboplatin & Paclitaxel 2. Cisplatin & Paclitaxel |
Seems to have inferior OS |
Pfisterer et al. 2006 (AGO-OVAR 2.5) | 1999-2002 | Phase III (C) | Carboplatin & Gemcitabine | Inferior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
21-day cycle for 6 to 10 cycles
Regimen variant #2, 300 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bolis et al. 2001 (ARGO 96) | 1991-NR | Phase III (C) | Carboplatin & Epirubicin | Did not meet primary endpoint of ORR |
Chemotherapy
- Carboplatin (Paraplatin) 300 mg/m2 IV once on day 1
28-day cycle for 5 cycles
References
- ARGO 96: Bolis G, Scarfone G, Giardina G, Villa A, Mangili G, Melpignano M, Presti M, Tateo S, Franchi M, Parazzini F; Associazione per la Ricerca in Ginecologia Oncologia Study Group. Carboplatin alone vs carboplatin plus epidoxorubicin as second-line therapy for cisplatin- or carboplatin-sensitive ovarian cancer. Gynecol Oncol. 2001 Apr;81(1):3-9. link to original article contains protocol PubMed
- ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. link to original article contains verified protocol PubMed NCT00002894
- 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 NCT00102414
Carboplatin & Docetaxel
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Regimen variant #1, AUC 2/35, 3 weeks out of 4
Study | Years of enrollment | Evidence |
---|---|---|
Kushner et al. 2007 | NR in abstract | Phase II |
Note: BSA was capped at 2 m2.
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV over 30 minutes once per day on days 1, 8, 15, given second
- Docetaxel (Taxotere) 35 mg/m2 (maximum dose of 70 mg) IV over 60 minutes once per day on days 1, 8, 15, given first
Supportive medications
- Dexamethasone (Decadron) 4 mg PO the evening before, the morning of, and evening after Docetaxel (Taxotere)
- 5-HT3 antagonist once per day on days 1, 8, 15, prior to chemotherapy
- Phenothiazine or 5-HT3 antagonist as needed as an outpatient
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, immediately prior to Docetaxel (Taxotere)
28-day cycle for 6 cycles
Regimen variant #2, AUC 5/75
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Strauss et al. 2007 | 2000-2003 | Phase II | ||
Vergote et al. 2016 (FAR-131) | 2009-NR | Phase III (C) | DCb & Farletuzumab | Did not meet primary endpoint of PFS |
Shi et al. 2021 (SOC-1) | 2012-2019 | Non-randomized portion of phase III RCT |
Note: this is the lower bound of carboplatin dosing specified by FAR-131.
Preceding treatment
- SOC-1: Secondary cytoreduction versus no surgical intervention
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 1, given second
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1, given first
Supportive medications
- Corticosteroids given twice on day 1; 12 hours and 30 minutes prior to Docetaxel (Taxotere)
- Prophylactic 5-HT3 antagonist
21-day cycle for 6 cycles
Regimen variant #3, AUC 6/75
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vergote et al. 2016 (FAR-131) | 2009-NR | Phase III (C) | Carboplatin, Paclitaxel, Farletuzumab | Did not meet primary endpoint of PFS |
Note: this is the upper bound of carboplatin dosing specified by FAR-131.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- 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
- 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
- FAR-131: Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, Weil SC, Bamias A, Fujiwara K, Ochiai K, Poole C, Gorbunova V, Wang W, O'Shannessy D, Herzog TJ. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol. 2016 Jul 1;34(19):2271-8. Epub 2016 Mar 21. link to original article contains verified protocol PubMed NCT00849667
- SOC-1: Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, Jia H, Huang X, Cai Y, Yin S, Jiang R, Tian W, Gao W, Liu J, Yang H, Cheng X, Zang R. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):439-449. Epub 2021 Mar 8. link to original article contains protocol PubMed NCT01611766
Carboplatin & Doxorubicin liposomal
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CD: Carboplatin & Doxil (Pegylated liposomal doxorubicin)
PLDC: Pegylated Liposomal Doxorubicin & Carboplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujade-Lauraine et al. 2010 (CALYPSO) | 2005-2007 | Phase III (E-switch-ic) | Carboplatin & Paclitaxel | Superior PFS Median PFS: 11.3 vs 9.4 mo (HR 0.82, 95% CI 0.72-0.94) |
Sehouli et al. 2016 (HECTOR) | 2007-2009 | Randomized Phase II (C) | Carboplatin & Topotecan | Did not meet primary endpoint of PFS12 |
Pignata et al. 2021 (MITO 16) | 2013-2016 | Phase 3 (C) | 1. Carboplatin, PLD, Bevacizumab 2. Carboplatin, Gemcitabine, Bevacizumab 3. Carboplatin, Paclitaxel, Bevacizumab |
Inferior PFS |
CALYPSO: Caelyx (Pegylated liposomal doxorubicin) in Platinum Sensitive Ovarian patients
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Pegylated liposomal doxorubicin (Doxil) 30 mg/m2 IV once on day 1
Supportive medications
- "Antiemetics, including a serotonin 5-HT3 antagonist and corticosteroid"
28-day cycle for 6 or more cycles, depending on response and toxicity
References
- 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 NCT00189553
- Update: Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Pujade Lauraine E. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012 Aug 7;107(4):588-91. Epub 2012 Jul 26. link to original article contains verified protocol link to PMC article PubMed
- HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article contains verified protocol PubMed NCT00437307
- MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains protocol PubMed NCT01802749
- INOVATYON: NCT01379989
Carboplatin, Doxorubicin liposomal, Bevacizumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfisterer et al. 2020 (AGO-OVAR 2.21/ENGOT-ov 18) | 2013-2015 | Phase III (E-switch-ic) | Carboplatin, Gemcitabine, Bevacizumab | Seems to have superior PFS Median PFS: 13.3 vs 11.6 mo (HR 0.81, 95% CI 0.68-0.96) |
Pignata et al. 2021 (MITO 16) | 2013-2016 | Phase 3 (E-esc) | 1. Carboplatin & PLD 2. Carboplatin & Gemcitabine 3. Carboplatin & Paclitaxel |
Superior PFS Median PFS: 11.8 vs 8.8 mo (HR 0.51, 95% CI 0.41-0.65) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Pegylated liposomal doxorubicin (Doxil) 30 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycle for 6 or more cycles
Subsequent treatment
References
- AGO-OVAR 2.21/ENGOT-ov 18: Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. Epub 2020 Apr 16. link to original article contains protocol PubMed NCT01837251
- MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains protocol PubMed NCT01802749
Carboplatin & Gemcitabine (GCb)
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GCb: Gemcitabine & Carboplatin
Regimen variant #1, limited duration
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfisterer et al. 2006 (AGO-OVAR 2.5) | 1999-2002 | Phase III (E-RT-esc) | Carboplatin | Superior PFS |
Aghajanian et al. 2012 (OCEANS) | 2007-2010 | Phase III (C) | Carboplatin, Gemcitabine, Bevacizumab | Inferior PFS |
Coleman et al. 2017 (NRG/GOG-0213) | 2007-2011 | Non-randomized |
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 6 to 10 cycles
Regimen variant #2, indefinite
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sehouli et al. 2016 (HECTOR) | 2007-2009 | Randomized Phase II (C) | Carboplatin & Topotecan | Did not meet primary endpoint of PFS12 |
Pignata et al. 2021 (MITO 16) | 2013-2016 | Phase 3 (C) | 1. Carboplatin, PLD, Bevacizumab 2. Carboplatin, Gemcitabine, Bevacizumab 3. Carboplatin, Paclitaxel, Bevacizumab |
Inferior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- 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 NCT00102414
- OCEANS: Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. Epub 2012 Apr 23. link to original article contains verified protocol link to PMC article PubMed NCT00434642
- 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
- HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article contains verified protocol PubMed NCT00437307
- 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 link to PMC article PubMed NCT00565851
- Update: Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, Kim JW, Park SY, Kim BG, Nam JH, Fujiwara K, Walker JL, Casey AC, Alvarez Secord A, Rubin S, Chan JK, DiSilvestro P, Davidson SA, Cohn DE, Tewari KS, Basen-Engquist K, Huang HQ, Brady MF, Mannel RS. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019 Nov 14;381(20):1929-1939. link to original article contains verified protocol PubMed
- MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains protocol PubMed NCT01802749
Carboplatin & Gemcitabine (GCb) & Bevacizumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Aghajanian et al. 2012 (OCEANS) | 2007-2010 | Phase III (E-RT-esc) | GCb | Superior PFS (HR 0.48, 95% CI 0.39-0.61) |
Coleman et al. 2017 (NRG/GOG-0213) | 2007-2011 | Non-randomized | ||
Pfisterer et al. 2020 (AGO-OVAR 2.21/ENGOT-ov 18) | 2013-2015 | Phase III (C) | Carboplatin, Doxil, Bevaciuzmab | Seems to have inferior PFS |
Pignata et al. 2021 (MITO 16) | 2013-2016 | Phase 3 (E-esc) | 1. Carboplatin & PLD 2. Carboplatin & Gemcitabine 3. Carboplatin & Paclitaxel |
Superior PFS Median PFS: 11.8 vs 8.8 mo (HR 0.51, 95% CI 0.41-0.65) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1, given first
21-day cycle for 6 to 10 cycles, based on response and protocol
Subsequent treatment
References
- OCEANS: Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. Epub 2012 Apr 23. link to original article contains verified protocol link to PMC article PubMed NCT00434642
- 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
- 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 link to PMC article PubMed NCT00565851
- Update: Coleman RL, Spirtos NM, Enserro D, Herzog TJ, Sabbatini P, Armstrong DK, Kim JW, Park SY, Kim BG, Nam JH, Fujiwara K, Walker JL, Casey AC, Alvarez Secord A, Rubin S, Chan JK, DiSilvestro P, Davidson SA, Cohn DE, Tewari KS, Basen-Engquist K, Huang HQ, Brady MF, Mannel RS. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019 Nov 14;381(20):1929-1939. link to original article contains verified protocol PubMed
- AGO-OVAR 2.21/ENGOT-ov 18: Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, Sehouli J, Canzler U, Schmalfeldt B, Dean AP, Hein A, Zeimet AG, Hanker LC, Petit T, Marmé F, El-Balat A, Glasspool R, de Gregorio N, Mahner S, Meniawy TM, Park-Simon TW, Mouret-Reynier MA, Costan C, Meier W, Reinthaller A, Goh JC, L'Haridon T, Baron Hay S, Kommoss S, du Bois A, Kurtz JE; AGO-OVAR 2.21/ENGOT-ov 18 Investigators. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 May;21(5):699-709. Epub 2020 Apr 16. link to original article contains protocol PubMed NCT01837251
- MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains protocol PubMed NCT01802749
Carboplatin & Paclitaxel (CP)
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CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin
Regimen variant #1, AUC 5/175, limited duration
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coleman et al. 2017 (NRG/GOG-0213) | 2007-2011 | Phase III (C) | Carboplatin, Paclitaxel, Bevacizumab | Might have inferior OS |
Vergote et al. 2019 (OAS 07OVA) | 2009-2013 | Phase III (C) | Carboplatin & Paclitaxel micellar | Non-inferior PFS |
Pignata et al. 2017 (MITO-8) | 2009-2015 | Phase III (C) | NPBC | Did not meet primary endpoint of OS |
Vergote et al. 2016 (FAR-131) | 2009-NR | Phase III (C) | Carboplatin, Paclitaxel, Farletuzumab | Did not meet primary endpoint of PFS |
Shi et al. 2021 (SOC-1) | 2012-2019 | Non-randomized portion of phase III RCT |
Preceding treatment
- SOC-1: Secondary cytoreduction versus no surgical intervention
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- (varies depending on reference):
- Corticosteroids and prophylactic 5-HT3 antagonist
- Premedication (with steroids & antihistamines) prior to Paclitaxel (Taxol)
21-day cycle for 6 to 9 cycles
Subsequent treatment
- MITO-8, upon progression: Non-platinum-based chemotherapy (NPBC)
Regimen variant #2, AUC 5/175, indefinite
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Parmar et al. 2003 (ICON4) | 1996-2002 | Phase III (E-esc) | Carboplatin | Seems to have superior OS |
Pujade-Lauraine et al. 2010 (CALYPSO) | 2005-2007 | Phase III (C) | Carboplatin & PLD | Inferior PFS |
Sehouli et al. 2016 (HECTOR) | 2007-2009 | Randomized Phase II (C) | Carboplatin & Topotecan | Did not meet primary endpoint of PFS12 |
Coleman et al. 2017 (NRG/GOG-0213) | 2007-2011 | Phase III (C) | TC & Bevacizumab | Might have inferior OS |
Oza et al. 2014 (D0810C00041) | 2010 | Randomized Phase II (C) | Carboplatin, Olaparib, Paclitaxel | Inferior PFS |
Pignata et al. 2021 (MITO 16) | 2013-2016 | Phase 3 (C) | 1. Carboplatin, PLD, Bevacizumab 2. Carboplatin, Gemcitabine, Bevacizumab 3. Carboplatin, Paclitaxel, Bevacizumab |
Inferior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- (varies depending on reference):
- Corticosteroids and prophylactic 5-HT3 antagonist
- Premedication (with steroids & antihistamines) prior to Paclitaxel (Taxol)
21-day cycles
Regimen variant #3, AUC 6/175, limited duration
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vergote et al. 2019 (OAS 07OVA) | 2009-2013 | Phase III (C) | Carboplatin & Paclitaxel micellar | Non-inferior PFS |
Vergote et al. 2016 (FAR-131) | 2009-NR | Phase III (C) | TC & Farletuzumab | Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycle for 6 cycles
Regimen variant #4, AUC 6/175, indefinite
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oza et al. 2014 (D0810C00041) | 2010 | Randomized Phase II (C) | Carboplatin, Olaparib, Paclitaxel | Inferior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- (varies depending on reference):
- Corticosteroids and prophylactic 5-HT3 antagonist
- Premedication (with steroids & antihistamines) prior to Paclitaxel (Taxol)
21-day cycles
References
- ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. link to original article contains verified protocol PubMed NCT00002894
- 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 NCT00189553
- Update: Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, Bonaventura T, Vergote I, Piccirillo MC, Fossati R, Gebski V, Pujade Lauraine E. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012 Aug 7;107(4):588-91. Epub 2012 Jul 26. link to original article contains verified protocol link to PMC article PubMed
- 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 NCT01081951
- FAR-131: Vergote I, Armstrong D, Scambia G, Teneriello M, Sehouli J, Schweizer C, Weil SC, Bamias A, Fujiwara K, Ochiai K, Poole C, Gorbunova V, Wang W, O'Shannessy D, Herzog TJ. A randomized, double-blind, placebo-controlled, phase III study to assess efficacy and safety of weekly farletuzumab in combination with carboplatin and taxane in patients with ovarian cancer in first platinum-sensitive relapse. J Clin Oncol. 2016 Jul 1;34(19):2271-8. Epub 2016 Mar 21. link to original article PubMed NCT00849667
- HECTOR: Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P, Woopen H, Petru E, Hanker LC, Keil E, Wimberger P, Klare P, Kurzeder C, Hilpert F, Belau AK, Zeimet A, Bover-Barcelo I, Canzler U, Mahner S, Meier W; NOGGO; AGO; GEICO-ENGOT-GCIG. Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol. 2016 Dec;27(12):2236-2241. Epub 2016 Oct 26. link to original article contains verified protocol PubMed NCT00437307
- 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 link to PMC article PubMed NCT00565851
- 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 NCT00657878
- OAS 07OVA: Vergote I, Bergfeldt K, Franquet A, Lisyanskaya AS, Bjermo H, Heldring N, Buyse M, Brize A. A randomized phase III trial in patients with recurrent platinum sensitive ovarian cancer comparing efficacy and safety of paclitaxel micellar and Cremophor EL-paclitaxel. Gynecol Oncol. 2020 Feb;156(2):293-300. Epub 2019 Dec 9. link to original article contains protocol PubMed NCT00989131
- MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains protocol PubMed NCT01802749
- SOC-1: Shi T, Zhu J, Feng Y, Tu D, Zhang Y, Zhang P, Jia H, Huang X, Cai Y, Yin S, Jiang R, Tian W, Gao W, Liu J, Yang H, Cheng X, Zang R. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):439-449. Epub 2021 Mar 8. link to original article contains protocol PubMed NCT01611766
Carboplatin, Olaparib, Paclitaxel
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oza et al. 2014 (D0810C00041) | 2010 | Randomized Phase II (E-esc) | Carboplatin & Paclitaxel | Superior PFS Median PFS: 12.2 vs 9.6 mo (HR 0.51, 95% CI 0.34-0.77) |
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 4 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m2 IV once on day 1
Targeted therapy
- Olaparib (Lynparza) as follows:
- Cycles 1 to 6: 200 mg PO twice per day on days 1 to 10
- Cycle 7 onwards: 400 mg PO twice per day
21-day cycles
References
- 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 NCT01081951
Carboplatin & Paclitaxel (CP) & Bevacizumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coleman et al. 2017 (NRG/GOG-0213) | 2007-2011 | Phase III (E-RT-esc) | Carboplatin & Paclitaxel | Might have superior OS Median OS: 42.2 vs 37.3 mo (HR 0.83, 95% CI 0.68-1.005) |
Pignata et al. 2021 (MITO 16) | 2013-2016 | Phase 3 (E-esc) | 1. Carboplatin & PLD 2. Carboplatin & Gemcitabine 3. Carboplatin & Paclitaxel |
Superior PFS Median PFS: 11.8 vs 8.8 mo (HR 0.51, 95% CI 0.41-0.65) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- NRG/GOG-0213: Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, Kim BG, Fujiwara K, Tewari KS, O'Malley DM, Davidson SA, Rubin SC, DiSilvestro P, Basen-Engquist K, Huang H, Chan JK, Spirtos NM, Ashfaq R, Mannel RS. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):779-791. Epub 2017 Apr 21. link to original article link to PMC article PubMed NCT00565851
- MITO 16: Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, Bamias A, Salutari V, Selle F, Frezzini S, De Giorgi U, Pautier P, Bologna A, Orditura M, Dubot C, Gadducci A, Mammoliti S, Ray-Coquard I, Zafarana E, Breda E, Favier L, Ardizzoia A, Cinieri S, Largillier R, Sambataro D, Guardiola E, Lauria R, Pisano C, Raspagliesi F, Scambia G, Daniele G, Perrone F; MITO16b/MANGO–OV2/ENGOT–ov17 Investigators. Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):267-276. link to original article contains protocol PubMed NCT01802749
Cisplatin & Gemcitabine (GC)
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Rose et al. 2003 | NR in abstract | Phase II |
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 & 8, given second
- Gemcitabine (Gemzar) 750 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
Supportive medications
- 5-HT3 antagonists
- Corticosteroids
- Prochlorperazine (Compazine)
- Magnesium supplementation with Cisplatin (Platinol)
21-day cycles
References
- 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Parmar et al. 2003 (ICON4) | 1996-2002 | Phase III (E-esc) | Carboplatin | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycles
References
- ICON4: Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Tropé C; ICON; AGO. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. link to original article contains verified protocol PubMed NCT00002894
Etoposide monotherapy
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Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Rose et al. 1998 | 1992-1995 | 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
- Rose PG, Blessing JA, Mayer AR, Homesley HD; Gynecologic Oncology Group. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. link to original article contains verified protocol PubMed
nab-Paclitaxel monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Teneriello et al. 2009 | 2005-2006 | Phase II |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV over 30 minutes once on day 1
21-day cycle for 6 to 8 cycles
References
- 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 | Years of enrollment | Evidence |
---|---|---|
Swisher et al. 2016 (ARIEL2) | 2013-2014 | Phase II (RT) |
Targeted therapy
- Rucaparib (Rubraca) 600 mg PO twice per day
28-day cycles
References
- ARIEL2: Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. Epub 2016 Nov 28. link to original article contains verified protocol PubMed NCT01891344
Maintenance after second-line therapy for platinum-sensitive disease
Niraparib monotherapy
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Regimen variant #1, 200 mg/day
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2021 (NORA) | 2017-2019 | Phase III (E-esc) | Placebo | Superior PFS |
Note: after a mid-protocol amendment, this was the dosing for patients with bodyweight of less than 77 kg, or a platelet count of less than 150 × 109/L.
Preceding treatment
- Platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
Targeted therapy
- Niraparib (Zejula) 200 mg PO once per day
Continued indefinitely
Regimen variant #2, 300 mg/day
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mirza et al. 2016 (NOVA) | 2013-NR | Phase III (E-RT-esc) | Placebo | Superior PFS1 Median PFS: 9.3 mo vs 3.9 mo (HR 0.45, 95% CI 0.34-0.61) |
Wu et al. 2021 (NORA) | 2017-2019 | Phase III (E-esc) | Placebo | Superior PFS |
1Reported efficacy is for the overall non-gBRCA cohort.
Note: in NORA, after a mid-protocol amendment, this was the dosing for patients with bodyweight of 77 kg or more, and a platelet count of 150 × 109/L or more.
Preceding treatment
- Platinum-containing chemotherapy; neither specific agents, combinations, nor doses are specified in the protocol.
Targeted therapy
- Niraparib (Zejula) 300 mg PO once per day
Continued indefinitely
References
- 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 NCT01847274
- Subgroup analysis: Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, Waters J, Berek JS, Woie K, Oza AM, Canzler U, Gil-Martin M, Lesoin A, Monk BJ, Lund B, Gilbert L, Wenham RM, Benigno B, Arora S, Hazard SJ, Mirza MR. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Nov 10;37(32):2968-2973. Epub 2019 Jun 7. link to original article PubMed
- Update: Mirza MR, Benigno B, Dørum A, Mahner S, Bessette P, Barceló IB, Berton-Rigaud D, Ledermann JA, Rimel BJ, Herrstedt J, Lau S, du Bois A, Casado Herráez A, Kalbacher E, Buscema J, Lorusso D, Vergote I, Levy T, Wang P, de Jong FA, Gupta D, Matulonis UA. Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial. Gynecol Oncol. 2020 Nov;159(2):442-448. Epub 2020 Sep 25. link to original article PubMed
- NORA: Wu XH, Zhu JQ, Yin RT, Yang JX, Liu JH, Wang J, Wu LY, Liu ZL, Gao YN, Wang DB, Lou G, Yang HY, Zhou Q, Kong BH, Huang Y, Chen LP, Li GL, An RF, Wang K, Zhang Y, Yan XJ, Lu X, Lu WG, Hao M, Wang L, Cui H, Chen QH, Abulizi G, Huang XH, Tian XF, Wen H, Zhang C, Hou JM, Mirza MR. Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2021 Apr;32(4):512-521. Epub 2021 Jan 14. link to original article contains protocol PubMed NCT03705156
Olaparib monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ledermann et al. 2012 (Study 19) | 2008-2010 | Randomized Phase II (E-RT-esc) | Placebo | Might have superior OS1 (HR 0.73, 95% CI 0.55-0.95) |
1Reported efficacy for Study 19 is based on the 2018 update; although p=0.02, the authors state that "the predefined threshold for statistical significance was not met."
Targeted therapy
- Olaparib (Lynparza) 400 mg PO twice per day
Continued indefinitely
References
- Study 19: Ledermann J1, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. link to original article contains verified protocol PubMed NCT00753545
- Update: Ledermann JA, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Fielding A, Spencer S, Rowe P, Lowe E, Hodgson D, Sovak MA, Matulonis U. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Oncol. 2016 Nov;17(11):1579-1589. Epub 2016 Sep 8. link to orignal article PubMed
- 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
- ICON9: NCT03278717
Rucaparib monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coleman et al. 2017 (ARIEL3) | 2014-2016 | Phase III (E-RT-esc) | Placebo | Superior PFS Median PFS 16.6 mo vs 5.4 mo (HR 0.23, 95% CI 0.16-0.34) |
Preceding treatment
Targeted therapy
- Rucaparib (Rubraca) 600 mg PO twice per day
28-day cycles
References
- 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 NCT01968213
- Update: Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. link to original article PubMed
- Update: Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, García-Donas J, Swisher EM, Cella D, Meunier J, Goble S, Cameron T, Maloney L, Mörk AC, Bedel J, Ledermann JA, Coleman RL. Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients With Recurrent Ovarian Carcinoma. J Clin Oncol. 2020 Oct 20;38(30):3494-3505. Epub 2020 Aug 24. link to original article link to PMC article PubMed
Relapsed or recurrent disease, platinum-resistant
Bevacizumab monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Burger et al. 2007 | 2002-2004 | Phase II |
Cannistra et al. 2007 | 2005 | Phase II |
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI; Gynecologic Oncology Group. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Nov 20;25(33):5165-71. Erratum in: J Clin Oncol. 2014 Nov 10;32(32):3686. link to original article contains verified protocol PubMed
- 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 | Years of enrollment | Evidence |
---|---|---|
Rose et al. 2003a | NR in abstract | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
Supportive medications
- Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2 (3 days)
- Diphenhydramine (Benadryl) 50 mg IV once on day 1, immediately prior to Docetaxel (Taxotere)
- Antiemetics as needed
21-day cycles
References
- Rose PG, Blessing JA, Ball HG, Hoffman J, Warshal D, DeGeest K, Moore DH; Gynecologic Oncology Group. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Feb;88(2):130-5. link to original article contains verified protocol PubMed
Doxorubicin pegylated liposomal monotherapy
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Regimen variant #1, 40 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lindemann et al. 2017 (Ovaresist) | 2002-2007 | Phase III (C) | Tamoxifen | Superior PFS |
Ferrandina et al. 2008 (MITO-3) | 2003-2007 | Phase III (E-switch-ic) | Gemcitabine | Might have inferior ORR |
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (C) | Pegylated liposomal doxorubicin & Bevacizumab | Inferior PFS |
Motohashi et al. 2020 (JGOG 3018) | 2010-2017 | Phase III (E-de-esc) | PLD; 50 mg/m2 | Inconclusive whether non-inferior PFS |
Pujade-Lauraine et al. 2021 (JAVELIN Ovarian 200) | 2016-2017 | Phase 3 (C) | 1. Avelumab 2. PLD & Avelumab |
Did not meet primary endpoints of PFS/OS |
Moore et al. 2021 (FORWARD I) | 2017-2018 | Phase 3 (C) | Mirvetuximab soravtansine | Did not meet primary endpoint of PFS |
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
- Pegylated liposomal doxorubicin (Doxil) 40 mg/m2 IV over 60 minutes once on day 1
Supportive medications
- Methylprednisolone (Solumedrol) 20 mg IV once on day 1; 30 minutes prior to Pegylated liposomal doxorubicin (Doxil)
28-day cycles
Regimen variant #2, 50 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Muggia et al. 1997 | 1994-1995 | Phase II (RT) | ||
Gordon et al. 2000 | NR-1998 | Phase II (RT) | ||
Gordon et al. 2001 (Doxil Study 30-49) | 1997-1999 | Phase III (E-RT-switch-ic) | Topotecan | Might have superior PFS |
Mutch et al. 2007 (B9E-US-S301) | 2002-2004 | Phase III (C) | Gemcitabine | Did not meet primary endpoint of PFS |
Vergote et al. 2009 (ASSIST-1) | 2003-2006 | Phase III (C) | Canfosfamide | Superior OS |
Monk et al. 2010 (OVA-301) | 2005-2007 | Phase III (C) | PLD & Trabectedin | Might have inferior OS1 |
Colombo et al. 2012 (CEPO906A2303) | 2005-2009 | Phase III (C) | Patupilone | Did not meet primary endpoint of OS |
Vergote et al. 2010 (ASSIST-5) | 2006-2007 | Phase III (C) | Canfosfamide & PLD | Did not meet primary endpoint of PFS |
Motohashi et al. 2020 (JGOG 3018) | 2010-2017 | Phase III (C) | PLD; 40 mg/m2 | Inconclusive whether non-inferior PFS |
Marth et al. 2016 (TRINOVA-2) | 2011-2013 | Phase III (C) | PLD & Trebananib | Did not meet primary endpoint of PFS |
Monk et al. 2020 (CR100983) | 2013-2018 | Phase III (C) | PLD & Trabectedin | Did not meet primary endpoint of OS |
Hamanishi et al. 2021 (NINJA) | 2015-2017 | Phase III (C) | Nivolumab | Did not meet primary endpoint of OS |
1Reported efficacy for OVA-301 is based on the 2012 update.
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 50 mg/m2 IV over 60 minutes once on day 1
28-day cycles
References
- Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, Roman L, Uziely B, Muderspach L, Garcia A, Burnett A, Greco FA, Morrow CP, Paradiso LJ, Liang LJ. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol. 1997 Mar;15(3):987-93. link to original article PubMed
- Gordon AN, Granai CO, Rose PG, Hainsworth J, Lopez A, Weissman C, Rosales R, Sharpington T. Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. J Clin Oncol. 2000 Sep;18(17):3093-100. link to original article contains protocol PubMed
- 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
- 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
- B9E-US-S301: Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. link to original article contains verified protocol PubMed content property of HemOnc.org NCT00191607
- 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
- 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 NCT00057720
- ASSIST-5: Vergote I, Finkler NJ, Hall JB, Melnyk O, Edwards RP, Jones M, Keck JG, Meng L, Brown GL, Rankin EM, Burke JJ, Boccia RV, Runowicz CD, Rose PG. Randomized phase III study of canfosfamide in combination with pegylated liposomal doxorubicin compared with pegylated liposomal doxorubicin alone in platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2010 Jul;20(5):772-80. link to original article PubMed NCT00350948
- 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 NCT00113607
- Update: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012 Oct;48(15):2361-8. Epub 2012 Apr 26. link to original article PubMed
- CEPO906A2303: Colombo N, Kutarska E, Dimopoulos M, Bae DS, Rzepka-Gorska I, Bidzinski M, Scambia G, Engelholm SA, Joly F, Weber D, El-Hashimy M, Li J, Souami F, Wing P, Engelholm S, Bamias A, Schwartz P. Randomized, open-label, phase III study comparing patupilone (EPO906) with pegylated liposomal doxorubicin in platinum-refractory or -resistant patients with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. J Clin Oncol. 2012 Nov 1;30(31):3841-7. Epub 2012 Sep 17. link to original article contains protocol PubMed NCT00262990
- AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains verified protocol PubMed NCT00976911
- 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
- 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
- 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 NCT01281254
- 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 link to PMC article PubMed NCT02728622
- CR100983: Monk BJ, Herzog TJ, Wang G, Triantos S, Maul S, Knoblauch R, McGowan T, Shalaby WSW, Coleman RL. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol. 2020 Mar;156(3):535-544. Epub 2020 Jan 8. link to original article contains protocol PubMed NCT01846611
- JGOG 3018: Motohashi T, Yabuno A, Michimae H, Ohishi T, Nonaka M, Takano M, Nishio S, Fujiwara H, Fujiwara K, Kondo E, Sugiyama T, Tabata T. Randomized phase III trial comparing pegylated liposomal doxorubicin (PLD) at 50 mg/m² versus 40 mg/m² in patients with platinum-refractory and -resistant ovarian carcinoma: the JGOG 3018 Trial. J Gynecol Oncol. 2021 Jan;32(1):e9. Epub 2020 Nov 10. link to original article contains protocol link to PMC article PubMed UMIN000003130
- FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article contains verified protocol PubMed NCT02631876
- JAVELIN Ovarian 200: Pujade-Lauraine E, Fujiwara K, Ledermann JA, Oza AM, Kristeleit R, Ray-Coquard IL, Richardson GE, Sessa C, Yonemori K, Banerjee S, Leary A, Tinker AV, Jung KH, Madry R, Park SY, Anderson CK, Zohren F, Stewart RA, Wei C, Dychter SS, Monk BJ. Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol. 2021 Jul;22(7):1034-1046. Epub 2021 Jun 15. link to original article contains protocol PubMed NCT02580058
- NINJA: Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, Matsumoto K, Ito K, Mandai M, Nakai H, Sakuragi N, Watari H, Takahashi N, Kato H, Hasegawa K, Yonemori K, Mizuno M, Takehara K, Niikura H, Sawasaki T, Nakao S, Saito T, Enomoto T, Nagase S, Suzuki N, Matsumoto T, Kondo E, Sonoda K, Aihara S, Aoki Y, Okamoto A, Takano H, Kobayashi H, Kato H, Terai Y, Takazawa A, Takahashi Y, Namba Y, Aoki D, Fujiwara K, Sugiyama T, Konishi I. Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol. 2021 Nov 20;39(33):3671-3681. Epub 2021 Sep 2. link to original article contains verified protocol link to PMC article PubMed JapicCTI-153004
- AGO-OVAR 2.29: NCT03353831
- EPIK-O: NCT04729387
- NItCHE: NCT04679064
- PROCEED: NCT01170650
Doxorubicin pegylated liposomal & Bevacizumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (E-RT-esc) | Pegylated liposomal doxorubicin | Superior PFS |
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 40 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
References
- AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains verified protocol PubMed NCT00976911
- 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
- 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
- NItCHE: NCT04679064
Doxorubicin pegylated liposomal & Gemcitabine
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Ferrandina et al. 2005 | NR in abstract | Phase II |
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 30 mg/m2 IV over 60 minutes once on day 1, given first
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
Supportive medications
- Metoclopramide (Reglan) once per day on days 1 & 8, prior to chemotherapy
21-day cycles
References
- 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Monk et al. 2010 (OVA-301) | 2005-2007 | Phase III (E-esc) | Pegylated liposomal doxorubicin | Might have superior OS1 (HR 0.86, 95% CI 0.72–1.02) |
1Reported efficacy is based on the 2012 update.
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 30 mg/m2 IV once on day 1
- Trabectedin (Yondelis) 1.1 mg/m2 IV over 3 hours once on day 1
21-day cycles
References
- 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 NCT00113607
- Update: Monk BJ, Herzog TJ, Kaye SB, Krasner CN, Vermorken JB, Muggia FM, Pujade-Lauraine E, Park YC, Parekh TV, Poveda AM. Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: overall survival analysis. Eur J Cancer. 2012 Oct;48(15):2361-8. Epub 2012 Apr 26. link to original article PubMed
Etoposide monotherapy
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Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Rose et al. 1998 | 1992-1995 | 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
- Rose PG, Blessing JA, Mayer AR, Homesley HD; Gynecologic Oncology Group. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998 Feb;16(2):405-10. link to original article contains verified protocol PubMed
Gemcitabine monotherapy
back to top |
Regimen variant #1, 2 weeks out of 3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mutch et al. 2007 (B9E-US-S301) | 2002-2004 | Phase III (E-switch-ic) | Pegylated liposomal doxorubicin | Did not meet primary endpoint of PFS |
Kurzeder et al. 2016 (PENELOPE) | 2013-2014 | Phase III (C) | Gemcitabine & Pertuzumab | Did not meet primary endpoint of PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8
21-day cycles
Regimen variant #2, 3 weeks out of 4
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ferrandina et al. 2008 (MITO-3) | 2003-2007 | Phase III (E-switch-ic) | Pegylated liposomal doxorubicin | Might have superior ORR |
Lheureux et al. 2021 (PHL-093) | 2014-2018 | Phase III (C) | Adavosertib & Gemcitabine | Inferior PFS |
Hamanishi et al. 2021 (NINJA) | 2015-2017 | Phase III (C) | Nivolumab | Did not meet primary endpoint of OS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
References
- B9E-US-S301: Mutch DG, Orlando M, Goss T, Teneriello MG, Gordon AN, McMeekin SD, Wang Y, Scribner DR Jr, Marciniack M, Naumann RW, Secord AA. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2007 Jul 1;25(19):2811-8. link to original article contains verified protocol PubMed NCT00191607
- 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
- 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 NCT01684878
- Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
- PHL-093: Lheureux S, Cristea MC, Bruce JP, Garg S, Cabanero M, Mantia-Smaldone G, Olawaiye AB, Ellard SL, Weberpals JI, Wahner Hendrickson AE, Fleming GF, Welch S, Dhani NC, Stockley T, Rath P, Karakasis K, Jones GN, Jenkins S, Rodriguez-Canales J, Tracy M, Tan Q, Bowering V, Udagani S, Wang L, Kunos CA, Chen E, Pugh TJ, Oza AM. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021 Jan 23;397(10271):281-292. link to original article PubMed NCT02151292
- NINJA: Hamanishi J, Takeshima N, Katsumata N, Ushijima K, Kimura T, Takeuchi S, Matsumoto K, Ito K, Mandai M, Nakai H, Sakuragi N, Watari H, Takahashi N, Kato H, Hasegawa K, Yonemori K, Mizuno M, Takehara K, Niikura H, Sawasaki T, Nakao S, Saito T, Enomoto T, Nagase S, Suzuki N, Matsumoto T, Kondo E, Sonoda K, Aihara S, Aoki Y, Okamoto A, Takano H, Kobayashi H, Kato H, Terai Y, Takazawa A, Takahashi Y, Namba Y, Aoki D, Fujiwara K, Sugiyama T, Konishi I. Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA). J Clin Oncol. 2021 Nov 20;39(33):3671-3681. Epub 2021 Sep 2. link to original article contains verified protocol link to PMC article PubMed JapicCTI-153004
- NItCHE: NCT04679064
Niraparib monotherapy
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Moore et al. 2019 (QUADRA) | 2015-2017 | Phase II (RT) |
Targeted therapy
- Niraparib (Zejula) 300 mg PO once per day
28-day cycles
References
- QUADRA: Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636-648. Epub 2019 Apr 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. link to original article contains protocol PubMed NCT02354586
Olaparib monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Gelmon et al. 2011 (D0810C00020) | 2008-2009 | Phase II |
Targeted therapy
- Olaparib (Lynparza) 400 mg PO twice per day
Continued indefinitely
References
- D0810C00020: 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
Paclitaxel monotherapy
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Regimen variant #1, 80 mg/m2 3 out of 4 weeks
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moore et al. 2021 (FORWARD I) | 2017-2018 | Phase 3 (C) | Mirvetuximab soravtansine | Did not meet primary endpoint of PFS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen variant #2, 80 mg/m2 weekly
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Markman et al. 2006 | NR | Phase II | ||
Lindemann et al. 2017 (Ovaresist) | 2002-2007 | Phase III (C) | Tamoxifen | Superior PFS |
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (C) | Paclitaxel & Bevacizumab | Inferior PFS |
Monk et al. 2014 (TRINOVA-1) | 2010-2012 | Phase III (C) | Paclitaxel & Trebananib | Inferior PFS |
Pignata et al. 2015 (MITO 11) | 2010-2013 | Randomized Phase II (C) | Paclitaxel & Pazopanib | Inferior PFS |
Kurzeder et al. 2016 (PENELOPE) | 2013-2014 | Phase III (C) | Paclitaxel & Pertuzumab | Did not meet primary endpoint of PFS |
Note: PENELOPE reports giving paclitaxel on days 1, 8, 15 of a 21-day cycle, which is identical to the schedule below. Ovaresist met its primary endpoint of superior HrQOL for the experimental (tamoxifen) arm but had inferior PFS (secondary endpoint) for the experimental arm, and this is the efficacy reported here.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22
Supportive medications
- Dexamethasone (Decadron) 10 mg IV or PO once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 25 to 50 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
- H2 blocker once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
28-day cycles
Regimen variant #3, 175 mg/m2, q3wk
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Eisenhauer et al. 1994 | 1991-1992 | Phase III (E-RT-switch-ic) | Paclitaxel; 135 mg/m2 | Seems to have superior PFS |
Gore et al. 1995 | 1992-1993 | Non-randomized | ||
ten Bokkel Huinink et al. 1997 | NR | Phase III (E-switch-ic) | Topotecan | Might have inferior TTP1 |
Cantù et al. 1999 | 1992-1995 | Phase III (E-de-esc) | CAP | Seems to have inferior OS |
Omura et al. 2003 | 1992-1995 | Phase III (C) | Paclitaxel; 250 mg/m2 | Seems to have inferior ORR |
Buda et al. 2004 | 1994-1999 | Phase III (C) | Epirubicin & Paclitaxel | Did not meet primary endpoint of OS |
1Reported efficacy for ten Bokkel Huinink et al. 1997 is based on the 2004 update.
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
- Omura et al. 2003 gave over 24 hours
21-day cycles
Regimen variant #4, 200 mg/m2, q3wk
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rosenberg et al. 2002 | 1995-1998 | Phase III (C) | Weekly paclitaxel; 67 mg/m2 | Did not meet primary endpoint of ORR |
Chemotherapy
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
21-day cycles
Regimen variant #5, with range
Study | Years of enrollment | Evidence |
---|---|---|
McGuire et al. 1989 | NR in abstract | Phase II |
Kohn et al. 1994 | NR in abstract | Phase II |
Of historic interest.
Chemotherapy
References
- 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
- 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
- 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
- Gore ME, Levy V, Rustin G, Perren T, Calvert AH, Earl H, Thompson JM. Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer. 1995 Oct;72(4):1016-9. link to original article link to PMC article PubMed
- 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
- 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
- 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
- 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
- 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
- Buda A, Floriani I, Rossi R, Colombo N, Torri V, Conte PF, Fossati R, Ravaioli A, Mangioni C; GONO. Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, GONO (Gruppo Oncologico Nord Ovest) group and IOR (Istituto Oncologico Romagnolo) group. Br J Cancer. 2004 Jun 1;90(11):2112-7. link to original article link to PMC article contains verified protocol PubMed
- 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
- AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains verified protocol PubMed NCT00976911
- 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
- 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
- TRINOVA-1: Monk BJ, Poveda A, Vergote I, Raspagliesi F, Fujiwara K, Bae DS, Oaknin A, Ray-Coquard I, Provencher DM, Karlan BY, Lhommé C, Richardson G, Rincón DG, Coleman RL, Herzog TJ, Marth C, Brize A, Fabbro M, Redondo A, Bamias A, Tassoudji M, Navale L, Warner DJ, Oza AM. Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): a randomised, multicentre, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 Jul;15(8):799-808. Epub 2014 Jun 17. link to original article PubMed NCT01204749
- 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
- MITO 11: Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol. 2015 May;16(5):561-8. Epub 2015 Apr 14. link to original article contains protocol PubMed NCT01644825
- 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 NCT01684878
- Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
- 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 link to PMC article PubMed NCT02728622
- FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article contains verified protocol PubMed NCT02631876
- AGO-OVAR 2.29: NCT03353831
- EPIK-O: NCT04729387
- GOG-3059: NCT04729608
- NItCHE: NCT04679064
- OVAL: NCT03398655
Paclitaxel & Bevacizumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (E-RT-esc) | Paclitaxel | Superior PFS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15, 22
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
References
- AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains verified protocol PubMed NCT00976911
- 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
- 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
- NItCHE: NCT04679064
Paclitaxel & Pazopanib
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pignata et al. 2015 (MITO 11) | 2010-2013 | Randomized Phase II (E-esc) | Paclitaxel | Superior PFS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Pazopanib (Votrient) 800 mg PO once per day
21-day cycles
References
- MITO 11: Pignata S, Lorusso D, Scambia G, Sambataro D, Tamberi S, Cinieri S, Mosconi AM, Orditura M, Brandes AA, Arcangeli V, Panici PB, Pisano C, Cecere SC, Di Napoli M, Raspagliesi F, Maltese G, Salutari V, Ricci C, Daniele G, Piccirillo MC, Di Maio M, Gallo C, Perrone F; MITO. Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial. Lancet Oncol. 2015 May;16(5):561-8. Epub 2015 Apr 14. link to original article contains protocol PubMed NCT01644825
Pazopanib monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Friedlander et al. 2010 | NR in abstract | Phase II |
Targeted therapy
- Pazopanib (Votrient) 800 mg PO once per day
Continued indefinitely
References
- 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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Regimen variant #1, 700 mg/m2
Study | Years of enrollment | Evidence |
---|---|---|
Miller et al. 2009 (GOG-0126Q) | 2004-2006 | Phase II |
Note: this is the dosage for patients with previous radiation therapy.
Chemotherapy
- Pemetrexed (Alimta) 700 mg/m2 IV over 10 minutes once on day 1
Supportive medications
- Folic acid 350 to 600 mcg PO once per day, starting 7 days before Pemetrexed (Alimta), to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once, 7 days before Pemetrexed (Alimta), then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after Pemetrexed (Alimta)
- No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed
21-day cycles
Regimen variant #2, 900 mg/m2
Study | Years of enrollment | Evidence |
---|---|---|
Miller et al. 2009 (GOG-0126Q) | 2004-2006 | Phase II |
Chemotherapy
- Pemetrexed (Alimta) 900 mg/m2 IV over 10 minutes once on day 1
Supportive medications
- Folic acid 350 to 600 mcg PO once per day, starting 7 days before Pemetrexed (Alimta), to continue throughout therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once, 7 days before Pemetrexed (Alimta), then 1000 mcg IM once every 9 weeks
- Dexamethasone (Decadron) 4 mg PO twice per day the day before, the day of, and day after Pemetrexed (Alimta)
- No NSAIDs (nonsteroidal anti-inflammatory drugs) for 2 days before or after pemetrexed
21-day cycles
References
- GOG-0126Q: Miller DS, Blessing JA, Krasner CN, Mannel RS, Hanjani P, Pearl ML, Waggoner SE, Boardman CH; Gynecologic Oncology Group. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol. 2009 Jun 1;27(16):2686-91. Epub 2009 Mar 30. link to original article contains verified protocol link to PMC article PubMed NCT00087087
Topotecan monotherapy
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Regimen variant #1, 4 mg/m2, 3 weeks out of 4 x 12 mo
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sehouli et al. 2010 (TOWERov) | 2005-2008 | Randomized Phase II (E-switch-ic) | Topotecan; q3wk | Did not meet primary endpoint of CBR |
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (C) | Bevacizumab & Topotecan | Inferior PFS |
Note: TOWER should not be confused with the trial by the same name in B-ALL.
Chemotherapy
- Topotecan (Hycamtin) 4 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for up to 13 cycles (1 year)
Regimen variant #2, 4 mg/m2, 3 weeks out of 4, indefinite
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (C) | Bevacizumab & Topotecan | Inferior PFS |
Moore et al. 2021 (FORWARD I) | 2017-2018 | Phase 3 (C) | Mirvetuximab soravtansine | Did not meet primary endpoint of PFS |
Chemotherapy
- Topotecan (Hycamtin) 4 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Regimen variant #3, 6.25 mg/m2, split dosing, q3wk x 12 mo
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sehouli et al. 2010 (TOWERov) | 2005-2008 | Randomized Phase II (C) | Topotecan; weekly | Did not meet primary endpoint of CBR |
Note: TOWER should not be confused with the trial by the same name in B-ALL.
Chemotherapy
- Topotecan (Hycamtin) 1.25 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycle for up to 18 cycles (1 year)
Regimen variant #4, 6.25 mg/m2, split dosing, q3wk, indefinite
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sehouli et al. 2008 | 1999-2004 | Phase III (C) | 1. Etoposide & Topotecan 2. Gemcitabine & Topotecan |
Did not meet primary endpoint of OS |
Meier et al. 2009 (AGO-OVAR 2.3) | 1998-2002 | Phase III (E-switch-ic) | Treosulfan | Superior OS |
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (C) | Topotecan & Bevacizumab | Inferior PFS |
Kurzeder et al. 2016 (PENELOPE) | 2013-2014 | Phase III (C) | Topotecan & Pertuzumab | Did not meet primary endpoint of PFS |
Moore et al. 2021 (FORWARD I) | 2017-2018 | Phase 3 (C) | Mirvetuximab soravtansine | Did not meet primary endpoint of PFS |
Note: this was the dosing used in third-line therapy in AGO-OVAR 2.3.
Chemotherapy
- Topotecan (Hycamtin) 1.25 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycles
Regimen variant #5, 7.5 mg/m2, split dosing, q3wk
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bookman et al. 1996 | NR | Phase II (RT) | ||
ten Bokkel Huinink et al. 1997 | NR | Randomized (E-RT-switch-ic) | Paclitaxel | Might have superior TTP1 |
Gordon et al. 2001 (Doxil Study 30-49) | 1997-1999 | Phase III (C) | Pegylated liposomal doxorubicin | Might have inferior PFS |
Meier et al. 2009 (AGO-OVAR 2.3) | 1998-2002 | Phase III (E-switch-ic) | Treosulfan | Superior OS |
1Reported efficacy for ten Bokkel Huinink et al. 1997 is based on the 2004 update.
Note: this was the dosing used in second-line therapy in AGO-OVAR 2.3.
Chemotherapy
- Topotecan (Hycamtin) 1.5 mg/m2 IV over 30 minutes once per day on days 1 to 5
21-day cycles
References
- Bookman MA, Malmström H, Bolis G, Gordon A, Lissoni A, Krebs JB, Fields SZ. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel. J Clin Oncol. 1998 Oct;16(10):3345-52. link to original article PubMed
- 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
- 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
- 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
- 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
- Sehouli J, Stengel D, Oskay-Oezcelik G, Zeimet AG, Sommer H, Klare P, Stauch M, Paulenz A, Camara O, Keil E, Lichtenegger W; North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2008 Jul 1;26(19):3176-82. link to original article contains verified protocol PubMed
- 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
- TOWER: Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T, Markmann S, Mahner S, Mueller L, Lorenz R, Nugent A, Wilke J, Kuznik A, Doering G, Wischnik A, Sommer H, Meerpohl HG, Schroeder W, Lichtenegger W, Oskay-Oezcelik G; North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. Topotecan weekly versus conventional 5-day schedule in patients with platinum-resistant ovarian cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol. 2011 Jan 10;29(2):242-8. Epub 2010 Nov 29. link to original article contains verified protocol PubMed NCT00170677
- AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains verified protocol PubMed NCT00976911
- 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
- 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
- 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 NCT01684878
- Update: Lorusso D, Hilpert F, González Martin A, Rau J, Ottevanger P, Greimel E, Lück HJ, Selle F, Colombo N, Kroep JR, Mirza MR, Berger R, Pardo B, Grischke EM, Berton-Rigaud D, Martinez-Garcia J, Vergote I, Redondo A, Cardona A, Bastière-Truchot L, du Bois A, Kurzeder C; PENELOPE trial investigators. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Int J Gynecol Cancer. 2019 Sep;29(7):1141-1147. Epub 2019 Aug 15. link to original article PubMed
- FORWARD I: Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. Epub 2021 Mar 2. link to original article contains verified protocol PubMed NCT02631876
- NItCHE: NCT04679064
Topotecan & Bevacizumab
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Regimen variant #1, topotecan 3 weeks out of 4
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (E-RT-esc) | Topotecan | Superior PFS |
Chemotherapy
- Topotecan (Hycamtin) 4 mg/m2 IV once per day on days 1, 8, 15
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Regimen variant #2, topotecan 6.25 mg/m2, split dosing, q3wk
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujade-Lauraine et al. 2014 (AURELIA) | 2009-2011 | Phase III (E-RT-esc) | Topotecan | Superior PFS |
Chemotherapy
- Topotecan (Hycamtin) 1.25 mg/m2 IV once per day on days 1 to 5
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- AURELIA: Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014 May 1;32(13):1302-8. Epub 2014 Mar 17. link to original article contains verified protocol PubMed NCT00976911
- 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
- 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
- NItCHE: NCT04679064
Trabectedin monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Krasner et al. 2007 | 2002-2004 | Phase II |
Chemotherapy
- Trabectedin (Yondelis) 0.58 mg/m2 IV over 3 hours once per day on days 1, 8, 15
28-day cycles
References
- 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Meier et al. 2009 (AGO-OVAR 2.3) | 1998-2002 | Phase III (E-switch-ic) | Topotecan | Inferior OS |
Sehouli et al. 2016 | 2002-2014 | Phase IIIb (C) | Treosulfan; PO | Might have superior OS |
Chemotherapy
References
- 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
- 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 | Years of enrollment | Evidence |
---|---|---|
Rothenberg et al. 2004 | NR in abstract | Phase II |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Rothenberg ML, Liu PY, Wilczynski S, Nahhas WA, Winakur GL, Jiang CS, Moinpour CM, Lyons B, Weiss GR, Essell JH, Smith HO, Markman M, Alberts DS; SWOG. Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study. Gynecol Oncol. 2004 Dec;95(3):506-12. link to original article contains protocol PubMed
Investigational agents
These are drugs under study with at least some promising results for this disease.