Endometrial cancer - null regimens

The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the main endometrial cancer page for current regimens.

Neoadjuvant therapy

Placebo

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kitson et al. 2018 (PREMIUM)	2015-2017	Phase III (C)	Metformin	Did not meet primary endpoint of posttreatment IHC expression of Ki-67

No active antineoplastic treatment prior to surgery.

Subsequent treatment

• Surgery

References

1. PREMIUM: Kitson SJ, Maskell Z, Sivalingam VN, Allen JL, Ali S, Burns S, Gilmour K, Latheef R, Slade RJ, Pemberton PW, Shaw J, Ryder WD, Kitchener HC, Crosbie EJ. PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a Multi-Center, Randomized Double-Blind, Placebo-Controlled Phase III Trial. Clin Cancer Res. 2019 Apr 15;25(8):2424-2432. Epub 2018 Dec 18. link to original article PubMed ISRCTN88589234

Adjuvant therapy

Observation

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Omura et al. 1985 (GOG 20)	1973-1982	Phase III (C)	Doxorubicin	Did not meet efficacy endpoints
Keys et al. 2004 (GOG 99)	1987-1995	Phase III (C)	RT	Inferior RFS
Hogberg et al. 2010 (EORTC 55991)	1996-2007	Phase III (C)	1. Cisplatin & Doxorubicin 2. Cisplatin & Epirubicin 3. Epirubicin & Paclitaxel 4. Carboplatin & Doxorubicin 5. Carboplatin & Paclitaxel	Seems to have inferior PFS
Hogberg et al. 2010 (MaNGO ILIADE-III)	1998-2007	Phase III (C)	Cisplatin & Doxorubicin	Did not meet primary endpoint of PFS

No further treatment.

Preceding treatment

• GOG 20, GOG 99, MaNGO ILIADE-III: Surgery
• EORTC 55991: Surgery, then RT

Subsequent treatment

• MaNGO ILIADE-III: RT

References

1. GOG 20: Omura GA, Blessing JA, Major F, Lifshitz S, Ehrlich CE, Mangan C, Beecham J, Park R, Silverberg S. A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group study. J Clin Oncol. 1985 Sep;3(9):1240-5. link to original article PubMed
2. GOG 99: Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG; Gynecologic Oncology Group. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Mar;92(3):744-51. Erratum in: Gynecol Oncol. 2004 Jul;94(1):241-2. link to original article PubMed
3. EORTC 55991/MaNGO ILIADE-III: Hogberg T, Signorelli M, de Oliveira CF, Fossati R, Lissoni AA, Sorbe B, Andersson H, Grenman S, Lundgren C, Rosenberg P, Boman K, Tholander B, Scambia G, Reed N, Cormio G, Tognon G, Clarke J, Sawicki T, Zola P, Kristensen G. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies. Eur J Cancer. 2010 Sep;46(13):2422-31. Epub 2010 Jul 7. link to original article link to PMC article PubMed NCT00005583

Placebo

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Barakat et al. 2006 (GOG 137A)	1997-2003	Phase III (C)	Estrogen replacement therapy	Did not meet primary endpoint of RFS

No active antineoplastic treatment. Note that this trial was stopped early due to the increased risk of ERT in the Women's Health Initiative trial, and should be considered inconclusive.

Preceding treatment

• Hysterectomy

References

1. GOG 137A: Barakat RR, Bundy BN, Spirtos NM, Bell J, Mannel RS; Gynecologic Oncology Group. Randomized double-blind trial of estrogen replacement therapy versus placebo in stage I or II endometrial cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2006 Feb 1;24(4):587-92. link to original article PubMed NCT00002976
2. SIENDO: NCT03555422

Maintenance after first-line therapy

Placebo

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
(DUO-E)	2020-ongoing	Phase III (C)	1. Durvalumab 2. Durvalumab & Olaparib	In progress

Preceding treatment

• Platinum-based chemotherapy

References

1. DUO-E: NCT04269200