Endometrial cancer

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Last updated on 2024-12-02:44 regimens on this page
63 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ESGO/ESHRE/ESGE==
*2023: Rodolakis et al. ESGO/ESHRE/ESGE guidelines for the fertility-sparing treatment of patients with endometrial carcinoma EuroPMC
==ESMO==
*2023: Koppikar et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer EuroPMC
*2022: Oaknin et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up EuroPMC
**2013: Colombo et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2010: Plataniotis & Castiglione. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Baekelandt & Castiglione. Endometrial carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
*2016: Colombo et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN Guidelines - Uterine Neoplasms
**2023: Abu-Rustum et al. Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. EuroPMC
**2018: Koh et al. Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology. EuroPMC
**2015: Koh et al. Uterine Sarcoma, Version 1.2016: Featured Updates to the NCCN Guidelines. EuroPMC
**2014: Koh et al. Uterine neoplasms, version 1.2014. EuroPMC
**2009: Greer et al. Uterine Neoplasms. Clinical Practice Guidelines in Oncology. EuroPMC
=Adjuvant therapy=
==Carboplatin & Doxorubicin==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hogberg et al. 2010 (EORTC 55991)	1996-2007 	Phase 3 (E-esc)	Observation	Seems to have longer PFS (primary endpoint)PFS60: 79% vs 72%(HR 0.64, 95 % CI 0.41-0.99)
====Preceding treatment====
*Surgery, then adjuvant RT
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
21-day cycle for 4 cycles
===References===
# EORTC 55991: Hogberg T, Signorelli M, Freire de Oliveira C, 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005583
==Carboplatin & Paclitaxel (CP)==
===Regimen variant #1, weekly===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Van Gorp et al. 2024 (KEYNOTE-B21)	2021-01-10 to 2022-10-31	Phase 3 (C)	CP & Pembrolizumab	Did not meet co-primary endpoint of DFSDFS24: 76% vs 75%(HR 0.98, 95% CI 0.76-1.27)
====Preceding treatment====
*Surgery
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 2 or 2.7 IV once on day 1
*Paclitaxel (Taxol) 60 mg/m2 IV once on day 1
7-day cycle for 12 cycles
====Subsequent treatment====
*Optional RT consolidation
===Regimen variant #2, 5/175===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Hogberg et al. 2010 (EORTC 55991) 	1996-2007 	Phase 3 (E-esc)	Observation 	Seems to have longer PFS (primary endpoint)PFS60: 79% vs 72%(HR 0.64, 95 % CI 0.41-0.99)
de Boer et al. 2018 (PORTEC-3) 	2006-2013 	Phase 3 (E-esc)	See link 	See link
Van Gorp et al. 2024 (KEYNOTE-B21)	2021-01-10 to 2022-10-31	Phase 3 (C) 	CP & Pembrolizumab	Did not meet co-primary endpoint of DFSDFS24: 76% vs 75%(HR 0.98, 95% CI 0.76-1.27)
====Preceding treatment====
*EORTC 55991 & PORTEC-3: Surgery, then adjuvant Cisplatin & RT
*KEYNOTE-B21: Surgery
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for varying durations: 4 cycles (EORTC 55991, PORTEC-3); 6 cycles (KEYNOTE-B21)
====Subsequent treatment====
*KEYNOTE-B21: Optional RT consolidation
===Regimen variant #3, 6/175===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Hogberg et al. 2010 (EORTC 55991) 	1996-2007 	Phase 3 (E-esc)	Observation 	Seems to have longer PFS (primary endpoint)PFS60: 79% vs 72%(HR 0.64, 95 % CI 0.41-0.99)
Matei et al. 2019 (GOG 258) 	2009-2014 	Phase 3 (C) 	Cisplatin & RT, then CP x 4	Did not meet primary endpoint of RFS
Van Gorp et al. 2024 (KEYNOTE-B21)	2021-01-10 to 2022-10-31	Phase 3 (C) 	CP & Pembrolizumab 	Did not meet co-primary endpoint of DFSDFS24: 76% vs 75%(HR 0.98, 95% CI 0.76-1.27)
====Preceding treatment====
*Hysterectomy and bilateral salpingo-oophorectomy, within 8 weeks
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for varying durations: 4 cycles (EORTC 55991); 6 cycles (GOG 258, KEYNOTE-B21)
====Subsequent treatment====
*KEYNOTE-B21: Optional RT consolidation
===References===
# EORTC 55991: Hogberg T, Signorelli M, Freire de Oliveira C, 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005583
# PORTEC-3: de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. Epub 2018 Feb 12. link to original article link to PMC article EuroPMC NCT00411138
## Update: de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Gribaudo S, Provencher D, Hanzen C, Kruitwagen RF, Smit VTHBM, Singh N, Do V, Lissoni A, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019 Sep;20(9):1273-1285. Epub 2019 Jul 22. Erratum in: Lancet Oncol. 2019 Sep;20(9):e468. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
# GOG 258: Matei D, Filiaci V, Randall ME, Mutch D, Steinhoff MM, DiSilvestro PA, Moxley KM, Kim YM, Powell MA, O'Malley DM, Spirtos NM, Small W Jr, Tewari KS, Richards WE, Nakayama J, Matulonis UA, Huang HQ, Miller DS. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med. 2019 Jun 13;380(24):2317-2326. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00942357
# JGOG2043: Nomura H, Aoki D, Michimae H, Mizuno M, Nakai H, Arai M, Sasagawa M, Ushijima K, Sugiyama T, Saito M, Tokunaga H, Matoda M, Nakanishi T, Watanabe Y, Takahashi F, Saito T, Yaegashi N; Japanese Gynecologic Oncology Group. Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):833-840. Epub 2019 Mar 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC UMIN000000522
# KEYNOTE-B21: Van Gorp T, Cibula D, Lv W, Backes F, Ortaç F, Hasegawa K, Lindemann K, Savarese A, Laenen A, Kim YM, Bodnar L, Barretina-Ginesta MP, Gilbert L, Pothuri B, Chen X, Flores MB, Levy T, Colombo N, Papadimitriou C, Buchanan T, Hanker LC, Eminowicz G, Rob L, Black D, Lichfield J, Lin G, Orlowski R, Keefe S, Lortholary A, Slomovitz B; ENGOT-en11/GOG-3053/KEYNOTE-B21 investigators. ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Ann Oncol. 2024 Nov;35(11):968-980. Epub 2024 Sep 14. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04634877
==Cisplatin & Doxorubicin==
CD: Cisplatin & Doxorubicin
AP: Adriamycin (Doxorubicin) & Platinol (Cisplatin)
===Regimen variant #1, 50/45, capped BSA===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Homesley et al. 2008 (GOG 184)	2000-2004 	Phase 3 (C)	CDP 	Did not meet primary endpoint of RFS
Note: Treatment was to start within 8 weeks of completion of RT.
====Preceding treatment====
*Surgery, then adjuvant RT
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 (maximum dose of 100 mg) IV once on day 1, given second
*Doxorubicin (Adriamycin) 45 mg/m2 (maximum dose of 90 mg) IV once on day 1, given first
====Supportive therapy====
*G-CSF, ONE of the following:
**Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11, or until ANC increases to 10,000/μL
**Pegfilgrastim (Neulasta) 6 mg SC once on day 2
*Dexamethasone (Decadron) 10 mg IV once on day 1, prior to chemotherapy
*5-HT3 antagonist
21-day cycle for 6 cycles
===Regimen variant #2, 50/50===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hogberg et al. 2010 (EORTC 55991)	1996-2007 	Phase 3 (E-esc)	Observation	Seems to have longer PFS (primary endpoint)PFS60: 79% vs 72%(HR 0.64, 95 % CI 0.41-0.99)
====Preceding treatment====
*Surgery, then adjuvant RT
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
28-day cycle for 4 cycles
===Regimen variant #3, 50/60 x 6===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Nomura et al. 2019 (JGOG2043)	2006-2011 	Phase 3 (C)	1. Carboplatin & Paclitaxel2. Cisplatin & Docetaxel	Did not meet primary endpoint of PFS
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1, given second
*Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1, given first
21-day cycle for 6 cycles
===Regimen variant #4, 50/60 x 8===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Randall et al. 2006 (GOG 122)	1992-2000 	Phase 3 (E-switch-ooc)	Whole abdominal irradiation	Longer OS (secondary endpoint)OS60: 55% vs 42%(aHR 0.68, 95% CI 0.52-0.89)
====Preceding treatment====
*Surgery, with optimal debulking
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 7: 60 mg/m2 IV once on day 1
====Supportive therapy====
*Normal saline at 500 mL/H for 2 hours prior to and after cisplatin
21-day cycle for 8 cycles
===References===
# GOG 122: Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2006 Jan 1;24(1):36-44. Epub 2005 Dec 5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GOG 184: Homesley HD, Filiaci V, Gibbons SK, Long HJ, Cella D, Spirtos NM, Morris RT, DeGeest K, Lee R, Montag A. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study. Gynecol Oncol. 2009 Mar;112(3):543-52. Epub 2008 Dec 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00006011
## Update: Spirtos NM, Enserro D, Homesley HD, Gibbons SK, Cella D, Morris RT, DeGeest K, Lee RB, Miller DS. The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): a randomized phase III NRG/Gynecologic Oncology Group (GOG) study. Gynecol Oncol. 2019 Jul;154(1):13-21. Epub 2019 Apr 30. link to original article link to PMC article EuroPMC
# EORTC 55991: Hogberg T, Signorelli M, Freire de Oliveira C, 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005583
# JGOG2043: Nomura H, Aoki D, Michimae H, Mizuno M, Nakai H, Arai M, Sasagawa M, Ushijima K, Sugiyama T, Saito M, Tokunaga H, Matoda M, Nakanishi T, Watanabe Y, Takahashi F, Saito T, Yaegashi N; Japanese Gynecologic Oncology Group. Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):833-840. Epub 2019 Mar 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC UMIN000000522
==Cisplatin & Epirubicin==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hogberg et al. 2010 (EORTC 55991)	1996-2007 	Phase 3 (E-esc)	Observation	Seems to have longer PFS (primary endpoint)PFS60: 79% vs 72%(HR 0.64, 95 % CI 0.41-0.99)
====Preceding treatment====
*Surgery, then adjuvant RT
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Epirubicin (Ellence) 50 mg/m2 IV once on day 1
28-day cycle for 4 cycles
===References===
# EORTC 55991: Hogberg T, Signorelli M, Freire de Oliveira C, 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005583
==Cisplatin & Ifosfamide==
CIM: Cisplatin, Ifosfamide, Mesna
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Wolfson et al. 2007 (GOG 150)	1993-2005 	Phase 3 (E-switch-ooc)	Whole abdominal irradiation	Might have longer OS1 (co-primary endpoint)Median OS: 48 vs 24 mo(HR 0.71, 95% CI 0.48-1.05)
1Median OS is not reported in the paper and is estimated from the K-M curve.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4, given first, at an infusion rate of approximately 1 mg/min
*Ifosfamide (Ifex) 1500 mg/m2 IV over 60 minutes once per day on days 1 to 4, given second, with mesna
====Supportive therapy====
*Mesna (Mesnex) 120 mg/m2 IV over 15 minutes once on day 1, then 1500 mg/m2/day IV continuous infusion over 96 hours, given second, with ifosfamide
*Suggested hydration: 1 liter of NS or 1/2 NS over several hours once per day on days 1 to 4, prior to chemotherapy
21-day cycle for 3 cycles
===References===
# GOG 150: Wolfson AH, Brady MF, Rocereto T, Mannel RS, Lee YC, Futoran RJ, Cohn DE, Ioffe OB. A Gynecologic Oncology Group randomized phase III trial of whole abdominal irradiation (WAI) vs cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007 Nov;107(2):177-85. Epub 2007 Sep 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00002546
==Cisplatin & RT==
Cisplatin & RT: Cisplatin & Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
de Boer et al. 2018 (PORTEC-3)	2006-2013 	Phase 3 (E-esc)	See link 	See link
Note: in PORTEC-3, radiation is to start within 4 to 6 weeks after surgery, and no later than 8 weeks; reported efficacy is based on the 2019 update.
====Preceding treatment====
*Surgery
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once per day on days 1 & 22
====Radiotherapy====
*External beam radiotherapy to the pelvis, 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36, 37 (27 fractions; total dose: 4860 cGy)
37-day course
====Subsequent treatment====
*Adjuvant Carboplatin & Paclitaxel x 4
===References===
# PORTEC-3: de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. Epub 2018 Feb 12. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00411138
## Update: de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Gribaudo S, Provencher D, Hanzen C, Kruitwagen RF, Smit VTHBM, Singh N, Do V, Lissoni A, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019 Sep;20(9):1273-1285. Epub 2019 Jul 22. Erratum in: Lancet Oncol. 2019 Sep;20(9):e468. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
#Lunchbox: Barlin JN, Mahar B, Ata A, Cormier B, Michelin D, Salani R, Backes F, Levinson K, Cantrell LA, Weinberg L, Wagreich A, Savage D, Gasson C, Denniston K, Martin J, McElrath T, Timmins PF. Lunchbox trial: A randomized phase III trial of cisplatin and irradiation followed by carboplatin and paclitaxel versus sandwich therapy of carboplatin and paclitaxel followed by irradiation then carboplatin and paclitaxel for advanced endometrial carcinoma. Gynecol Oncol. 2024 Jan;180:63-69. Epub 2023 Dec 5. link to original article EuroPMC
==Epirubicin & Paclitaxel (EP)==
EP: Epirubicin & Paclitaxel
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hogberg et al. 2010 (EORTC 55991)	1996-2007 	Phase 3 (E-esc)	Observation	Seems to have longer PFS (primary endpoint)PFS60: 79% vs 72%(HR 0.64, 95 % CI 0.41-0.99)
====Preceding treatment====
*Surgery, then adjuvant RT
====Chemotherapy====
*Epirubicin (Ellence) 60 mg/m2 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 4 cycles
===References===
# EORTC 55991: Hogberg T, Signorelli M, Freire de Oliveira C, 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005583
==Radiation therapy==
RT: Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Keys et al. 2004 (GOG 99) 	1987-1995 	Phase 3 (E-esc) 	Observation 	Longer RFI (primary endpoint)CIR24: 3% vs 12%(HR 0.42, 90% CI 0.25-0.73)
Maggi et al. 2006 	1990-1997 	Phase 3 (C) 	CAP 	Did not meet co-primary endpoints of PFS/OS
Susumu et al. 2007 (JGOG 2033)	1994-2000 	Phase 3 (C) 	CAP 	Did not meet primary endpoint of OS60
Homesley et al. 2008 (GOG 184)	2000-2004 	Non-randomized part of phase 3 RCT	 	
de Boer et al. 2018 (PORTEC-3)	2006-2013 	Phase 3 (C) 	Cisplatin & RT, then Carboplatin & Paclitaxel 	Seems to have shorter OS1
Randall et al. 2019 (GOG 249) 	2009-2013 	Phase 3 (C) 	Vaginal cuff brachytherapy, then Carboplatin & Paclitaxel	Did not meet primary endpoint of RFS
1Reported efficacy for PORTEC-3 is based on the 2019 update.
Note: in PORTEC-3, radiation is to start within 4 to 6 weeks after surgery, and no later than 8 weeks.
====Preceding treatment====
*Surgery
====Radiotherapy====
*External beam radiotherapy to the pelvis, 4000 to 5000 cGy
**If cervical involvement, brachytherapy boost
One course
====Subsequent treatment====
*GOG 184: Adjuvant CD x 6 versus CDP x 6
===References===
# 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 EuroPMC
# Maggi R, Lissoni A, Spina F, Melpignano M, Zola P, Favalli G, Colombo A, Fossati R. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial. Br J Cancer. 2006 Aug 7;95(3):266-71. Epub 2006 Jul 25. link to original article link to PMC article EuroPMC
# JGOG 2033: Susumu N, Sagae S, Udagawa Y, Niwa K, Kuramoto H, Satoh S, Kudo R; Japanese Gynecologic Oncology Group. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008 Jan;108(1):226-33. Epub 2007 Nov 9. link to original article EuroPMC
# GOG 184: Homesley HD, Filiaci V, Gibbons SK, Long HJ, Cella D, Spirtos NM, Morris RT, DeGeest K, Lee R, Montag A. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study. Gynecol Oncol. 2009 Mar;112(3):543-52. Epub 2008 Dec 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00006011
## Update: Spirtos NM, Enserro D, Homesley HD, Gibbons SK, Cella D, Morris RT, DeGeest K, Lee RB, Miller DS. The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): a randomized phase III NRG/Gynecologic Oncology Group (GOG) study. Gynecol Oncol. 2019 Jul;154(1):13-21. Epub 2019 Apr 30. link to original article link to PMC article EuroPMC
# PORTEC-3: de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. Epub 2018 Feb 12. link to original article link to PMC article EuroPMC NCT00411138
## Update: de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Gribaudo S, Provencher D, Hanzen C, Kruitwagen RF, Smit VTHBM, Singh N, Do V, Lissoni A, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019 Sep;20(9):1273-1285. Epub 2019 Jul 22. Erratum in: Lancet Oncol. 2019 Sep;20(9):e468. link to original article link to PMC article EuroPMC
#GOG 249: Randall ME, Filiaci V, McMeekin DS, von Gruenigen V, Huang H, Yashar CM, Mannel RS, Kim JW, Salani R, DiSilvestro PA, Burke JJ, Rutherford T, Spirtos NM, Terada K, Anderson PR, Brewster WR, Small W, Aghajanian CA, Miller DS. Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer. J Clin Oncol. 2019 Jul 20;37(21):1810-1818. Epub 2019 Apr 17. link to original article link to PMC article EuroPMC NCT00807768
=Non-endocrine therapy for advanced, recurrent, or metastatic disease=
==Bevacizumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Aghajanian et al. 2011 (GOG-0229E)	2006-2007 	Phase 2
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
===References===
# GOG-0229E: Aghajanian C, Sill MW, Darcy KM, Greer B, McMeekin DS, Rose PG, Rotmensch J, Barnes MN, Hanjani P, Leslie KK; Gynecologic Oncology Group. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Jun 1;29(16):2259-65. Epub 2011 May 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00301964
==Carboplatin monotherapy==
===Regimen variant #1, 300 mg/m2===
Study 	Dates of enrollment	Evidence	Efficacy
van Wijk et al. 2003	1985-10 to 1988-08 	Phase 2 	ORR: 13% (95% CI 6-25%)
Note: This dosing is intended for patients previously treated with chemotherapy.
====Chemotherapy====
*Carboplatin (Paraplatin) 300 mg/m2 IV over 30 minutes once on day 1
28-day cycles
===Regimen variant #2, 400 mg/m2===
Study 	Dates of enrollment	Evidence	Efficacy
van Wijk et al. 2003	1985-10 to 1988-08 	Phase 2 	ORR: 13% (95% CI 6-25%)
====Chemotherapy====
*Carboplatin (Paraplatin) 400 mg/m2 IV over 30 minutes once on day 1
28-day cycles
===References===
# van Wijk FH, Lhommé C, Bolis G, Scotto di Palumbo V, Tumolo S, Nooij M, Freire de Oliveira C, Vermorken JB; EORTC Gynaecological Cancer Group. Phase II study of carboplatin in patients with advanced or recurrent endometrial carcinoma: a trial of the EORTC Gynaecological Cancer Group. Eur J Cancer. 2003 Jan;39(1):78-85. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Carboplatin & Paclitaxel (CP)==
===Regimen variant #1, 4/175===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wu et al. 2024 (COMPASSION-16)	2021-09-11 to 2022-06-23	Phase 3 (C)	1a. CP & Cadonilimab1b. CP, Bevacizumab, Cadonilimab1c. TP & Cadonilimab1d. TP, Bevacizumab, Cadonilimab	Shorter OS (co-primary endpoint)Median OS: 22.8 vs NYR mo(HR 1.56, 95% CI 1.16-2.08)Shorter PFS (co-primary endpoint)Median PFS: 8.1 vs 12.7 mo(HR 1.61, 95% CI 1.25-2.04)
Note: this was the lower limit of carboplatin dosing in COMPASSION-16. To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 4 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===Regimen variant #2, 5/175===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Hoskins et al. 2001 	1995-1998 	Phase 2 	 	
Sorbe et al. 2007 	2000-2004 	Phase 2 	 	
Pectasides et al. 2008 	2004-01 to 2007-09 	Phase 2 	 	
Colombo et al. 2024 (AtTEnd) 	2018-10-03 to 2022-01-07	Phase 3 (C)	CP & Atezolizumab 	Shorter PFS (co-primary endpoint)Median PFS: 8.9 vs 10.1 mo(HR 1.35, 95% CI 1.10-1.64)
Mirza et al. 2023 (RUBY) 	2019-2022 	Phase 3 (C)	CP & Dostarlimab 	Shorter OS1 (co-primary endpoint)Median OS: 28.2 vs 44.6 mo(HR 1.45, 95% CI 1.12-1.85)
Eskander et al. 2023 (NRG GY018)	2019-07 to 2022-12 	Phase 3 (C)	CP & Pembrolizumab 	Shorter PFS2 (co-primary endpoint)PFS12: 38% vs 74%(HR 3.33, 95% CI 2.08-5.26)Shorter PFS3 (co-primary endpoint)Median PFS: 8.7 vs 13.1 mo(HR 1.85, 95% CI 1.41-2.44)
Westin et al. 2023 (DUO-E) 	2020-06-02 to 2022-04-20	Phase 3 (C)	1. CP & Durvalumab2. CP, Olaparib, Durvalumab 	Shorter PFS
Wu et al. 2024 (COMPASSION-16) 	2021-09-11 to 2022-06-23	Phase 3 (C)	1a. CP & Cadonilimab1b. CP, Bevacizumab, Cadonilimab1c. TP & Cadonilimab1d. TP, Bevacizumab, Cadonilimab	Shorter OS (co-primary endpoint)Median OS: 22.8 vs NYR mo(HR 1.56, 95% CI 1.16-2.08)Shorter PFS (co-primary endpoint)Median PFS: 8.1 vs 12.7 mo(HR 1.61, 95% CI 1.25-2.04)
1Reported efficacy for RUBY is based on the 2024 update.
2Reported efficacy for NRG GY018 is for the dMMR cohort.
3Reported efficacy for NRG GY018 is for the pMMR cohort.
Note: this was the lower limit of carboplatin dosing allowed in AtTEnd, DUO-E, and Hoskins et al. 2001. This was the upper bound of carboplatin dosing in COMPASSION-16. To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes 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 varying durations: 6 cycles (COMPASSION-16, DUO-E, NRG GY018, RUBY); 6 to 8 cycles (AtTEnd); 6 to 9 cycles (Pectasides et al. 2008); indefinitely (Hoskins et al. 2001, Sorbe et al. 2007)
===Regimen variant #3, 6/175===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Miller et al. 2020 (GOG0209) 	2003-2009 	Phase 3 (E-de-esc) 	TAP 	Non-inferior OS (primary endpoint)Median OS: 37 vs 41 mo(HR 1.002, 90% CI 0.9-1.12)
Powell et al. 2022 (GOG-0261)	2009-2014 	Phase 3 (E-switch-ic)	Ifosfamide & Paclitaxel 	Non-inferior OS (primary endpoint)Median OS: 37 vs 29 mo(HR 0.87, 90% CI 0.70-1.075)
Colombo et al. 2024 (AtTEnd) 	2018-10-03 to 2022-01-07	Phase 3 (C) 	CP & Atezolizumab 	Shorter PFS (co-primary endpoint)Median PFS: 8.9 vs 10.1 mo(HR 1.35, 95% CI 1.10-1.64)
Westin et al. 2023 (DUO-E) 	2020-06-02 to 2022-04-20	Phase 3 (C) 	1. CP & Durvalumab2. CP, Olaparib, Durvalumab	Shorter PFS
Note: this is the upper limit of carboplatin dosing in AtTEnd & DUO-E.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 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 varying durations: 6 cycles (DUO-E); 6 to 8 cycles (AtTEnd); 6 to 10 cycles (GOG-0261); 7 cycles (GOG0209)
===Regimen variant #4, 7/175===
Study 	Dates of enrollment	Evidence
Hoskins et al. 2001	1995-1998 	Phase 2
Note: this is the upper limit of carboplatin dosing allowed in Hoskins et al. 2001.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 7 IV once on day 1, given second
*Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
21-day cycles
===References===
# Hoskins PJ, Swenerton KD, Pike JA, Wong F, Lim P, Acquino-Parsons C, Le N. Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol. 2001 Oct 15;19(20):4048-53. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Sorbe B, Andersson H, Boman K, Rosenberg P, Kalling M. Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. Int J Gynecol Cancer. 2008 Jul-Aug;18(4):803-8. Epub 2007 Oct 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Pectasides D, Xiros N, Papaxoinis G, Pectasides E, Sykiotis C, Koumarianou A, Psyrri A, Gaglia A, Kassanos D, Gouveris P, Panayiotidis J, Fountzilas G, Economopoulos T. Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol. 2008 May;109(2):250-4. Epub 2008 Mar 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC content property of HemOnc.org
# Retrospective: Shechter-Maor G, Bruchim I, Ben-Harim Z, Altaras M, Fishman A. Combined chemotherapy regimen of carboplatin and paclitaxel as adjuvant treatment for papillary serous and clear cell endometrial cancer. Int J Gynecol Cancer. 2009 May;19(4):662-4. link to original article EuroPMC
# GOG0209: Miller DS, Filiaci VL, Mannel RS, Cohn DE, Matsumoto T, Tewari KS, DiSilvestro P, Pearl ML, Argenta PA, Powell MA, Zweizig SL, Warshal DP, Hanjani P, Carney ME, Huang H, Cella D, Zaino R, Fleming GF. Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209). J Clin Oncol. 2020 Nov 20;38(33):3841-3850. Epub 2020 Sep 29. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00063999
# GOG-0261: Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J Clin Oncol. 2022 Mar 20;40(9):968-977. Epub 2022 Jan 10. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00954174
# RUBY: Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. Epub 2023 Mar 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03981796
##Update: Powell MA, Bjørge L, Willmott L, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Gropp-Meier M, Stuckey A, Boere I, Gold MA, Segev Y, Gill SE, Gennigens C, Sebastianelli A, Shahin MS, Pothuri B, Monk BJ, Buscema J, Coleman RL, Slomovitz BM, Ring KL, Herzog TJ, Balas MM, Grimshaw M, Stevens S, Lai DW, McCourt C, Mirza MR. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial. Ann Oncol. 2024 Aug;35(8):728-738. Epub 2024 Jun 10. link to original article EuroPMC
#NRG GY018: Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel R, Shahin MS, Cantuaria GH, Girda E, Mathews C, Kavecansky J, Leath CA 3rd, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Al Baghdadi T, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2159-2170. Epub 2023 Mar 27. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03914612
#DUO-E: Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT04269200
#COMPASSION-13: Lou H, Cai H, Huang X, Li G, Wang L, Liu F, Qin W, Liu T, Liu W, Wang ZM, Li B, Xia Y, Wang J. Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study. Clin Cancer Res. 2024 Apr 15;30(8):1501-1508. link to original article link to PMC article EuroPMC NCT04868708
#AtTEnd: Colombo N, Biagioli E, Harano K, Galli F, Hudson E, Antill Y, Choi CH, Rabaglio M, Marmé F, Marth C, Parma G, Fariñas-Madrid L, Nishio S, Allan K, Lee YC, Piovano E, Pardo B, Nakagawa S, McQueen J, Zamagni C, Manso L, Takehara K, Tasca G, Ferrero A, Tognon G, Lissoni AA, Petrella M, Laudani ME, Rulli E, Uggeri S, Barretina Ginesta MP; AtTEnd study group. Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024 Sep;25(9):1135-1146. Epub 2024 Aug 2. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03603184
#COMPASSION-16: Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, Liao S, Ye Y, Yan P, Tang Q, Sun G, Liu T, Lu D, Hu M, Wang ZM, Li B, Xia M. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet. 2024 Oct 26;404(10463):1668-1676. Epub 2024 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04982237
==Carboplatin & Paclitaxel (CP) & Atezolizumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Colombo et al. 2024 (AtTEnd)	2018-10-03 to 2022-01-07	Phase 3 (E-esc)	CP 	Longer PFS (co-primary endpoint)Median PFS: 10.1 vs 8.9 mo(HR 0.74, 95% CI 0.61-0.91)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6 up to 8: AUC 5 or 6 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6 up to 8: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
===References===
#AtTEnd: Colombo N, Biagioli E, Harano K, Galli F, Hudson E, Antill Y, Choi CH, Rabaglio M, Marmé F, Marth C, Parma G, Fariñas-Madrid L, Nishio S, Allan K, Lee YC, Piovano E, Pardo B, Nakagawa S, McQueen J, Zamagni C, Manso L, Takehara K, Tasca G, Ferrero A, Tognon G, Lissoni AA, Petrella M, Laudani ME, Rulli E, Uggeri S, Barretina Ginesta MP; AtTEnd study group. Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024 Sep;25(9):1135-1146. Epub 2024 Aug 2. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03603184
==Carboplatin & Paclitaxel (CP) & Bevacizumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wu et al. 2024 (COMPASSION-16)	2021-09-11 to 2022-06-23	Phase 3 (C)	1a. CP & Cadonilimab1b. CP, Bevacizumab, Cadonilimab1c. TP & Cadonilimab1d. TP, Bevacizumab, Cadonilimab	Shorter OS (co-primary endpoint)Median OS: 22.8 vs NYR mo(HR 1.56, 95% CI 1.16-2.08)Shorter PFS (co-primary endpoint)Median PFS: 8.1 vs 12.7 mo(HR 1.61, 95% CI 1.25-2.04)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====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====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
===References===
#COMPASSION-13: Lou H, Cai H, Huang X, Li G, Wang L, Liu F, Qin W, Liu T, Liu W, Wang ZM, Li B, Xia Y, Wang J. Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study. Clin Cancer Res. 2024 Apr 15;30(8):1501-1508. link to original article link to PMC article EuroPMC NCT04868708
#COMPASSION-16: Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, Liao S, Ye Y, Yan P, Tang Q, Sun G, Liu T, Lu D, Hu M, Wang ZM, Li B, Xia M. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet. 2024 Oct 26;404(10463):1668-1676. Epub 2024 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04982237
==Carboplatin & Paclitaxel (CP), Bevacizumab, Cadonilimab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wu et al. 2024 (COMPASSION-16)	2021-09-11 to 2022-06-23	Phase 3 (E-esc)	1a. CP1b. CP & Bevacizumab1c. TP1d. TP & Bevacizumab	Longer OS (co-primary endpoint)Median OS: NYR vs 22.8 mo(HR 0.64, 95% CI 0.48-0.86)Longer PFS (co-primary endpoint)Median PFS: 12.7 vs 8.1 mo(HR 0.62, 95% CI 0.49-0.80)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 4 to 5 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
====Immunotherapy====
*Cadonilimab (AK-104) 10 mg/kg IV once on day 1
21-day cycles
===References===
#COMPASSION-13: Lou H, Cai H, Huang X, Li G, Wang L, Liu F, Qin W, Liu T, Liu W, Wang ZM, Li B, Xia Y, Wang J. Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study. Clin Cancer Res. 2024 Apr 15;30(8):1501-1508. link to original article link to PMC article EuroPMC NCT04868708
#COMPASSION-16: Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, Liao S, Ye Y, Yan P, Tang Q, Sun G, Liu T, Lu D, Hu M, Wang ZM, Li B, Xia M. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet. 2024 Oct 26;404(10463):1668-1676. Epub 2024 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04982237
==Carboplatin & Paclitaxel (CP) & Cadonilimab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wu et al. 2024 (COMPASSION-16)	2021-09-11 to 2022-06-23	Phase 3 (E-esc)	1a. CP1b. CP & Bevacizumab1c. TP1d. TP & Bevacizumab	Longer OS (co-primary endpoint)Median OS: NYR vs 22.8 mo(HR 0.64, 95% CI 0.48-0.86)Longer PFS (co-primary endpoint)Median PFS: 12.7 vs 8.1 mo(HR 0.62, 95% CI 0.49-0.80)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 4 to 5 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Cadonilimab (AK-104) 10 mg/kg IV once on day 1
21-day cycles
===References===
#COMPASSION-13: Lou H, Cai H, Huang X, Li G, Wang L, Liu F, Qin W, Liu T, Liu W, Wang ZM, Li B, Xia Y, Wang J. Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study. Clin Cancer Res. 2024 Apr 15;30(8):1501-1508. link to original article link to PMC article EuroPMC NCT04868708
#COMPASSION-16: Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, Liao S, Ye Y, Yan P, Tang Q, Sun G, Liu T, Lu D, Hu M, Wang ZM, Li B, Xia M. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet. 2024 Oct 26;404(10463):1668-1676. Epub 2024 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04982237
==Carboplatin & Paclitaxel (CP) & Dostarlimab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Mirza et al. 2023 (RUBY)	2019-2022 	Phase 3 (E-RT-esc)	CP 	Longer OS1 (co-primary endpoint)Median OS: 44.6 vs 28.2 mo(HR 0.69, 95% CI 0.54-0.89)
1Reported efficacy is based on the 2024 update.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 5 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Dostarlimab (Jemperli) as follows:
**Cycles 1 to 6: 500 mg IV once on day 1
**Cycles 7 to 32: 1000 mg IV once on day 1
21-day cycle for 6 cycles, then 42-day cycle for up to 26 cycles (3 years)
===References===
# RUBY: Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. Epub 2023 Mar 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03981796
##Update: Powell MA, Bjørge L, Willmott L, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Gropp-Meier M, Stuckey A, Boere I, Gold MA, Segev Y, Gill SE, Gennigens C, Sebastianelli A, Shahin MS, Pothuri B, Monk BJ, Buscema J, Coleman RL, Slomovitz BM, Ring KL, Herzog TJ, Balas MM, Grimshaw M, Stevens S, Lai DW, McCourt C, Mirza MR. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial. Ann Oncol. 2024 Aug;35(8):728-738. Epub 2024 Jun 10. link to original article EuroPMC
==Carboplatin & Paclitaxel (CP) & Durvalumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (E-RT-esc)	1. CP 	Longer PFS (primary endpoint)Median PFS: 10.2 vs 9.6 mo(HR 0.71, 95% CI 0.57-0.89)Superior dMMR subgroup PFS1 (secondary endpoint)Median PFS: NYR vs 7 mo(HR 0.42, 95% CI 0.22-0.80)
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (E-RT-esc)	2. CP, Olaparib, Durvalumab	Not formally compared
1PFS analysis of the dMMR subgroup was prespecified; FDA approval is for this subgroup.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 5 to 6 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Durvalumab (Imfinzi) as follows:
**Cycles 1 to 6: 1120 mg IV once on day 1
**Cycle 7 onwards: 1500 mg IV once on day 1
21-day cycle for 6 cycles, then 28-day cycles
===References===
#DUO-E: Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT04269200
==Carboplatin & Paclitaxel (CP), Olaparib, Durvalumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (E-esc)	1. CP 	Longer PFS (primary endpoint)Median PFS: 15.1 vs 9.6 mo(HR 0.55, 95% CI 0.43-0.69)
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (E-esc)	CP & Durvalumab	Not formally compared
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 5 to 6 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Durvalumab (Imfinzi) as follows:
**Cycles 1 to 6: 1120 mg IV once on day 1
**Cycle 7 onwards: 1500 mg IV once on day 1
====Targeted therapy====
*Olaparib (Lynparza) as follows:
**Cycle 7 onwards: 300 mg PO twice per day on days 1 to 28
21-day cycle for 6 cycles, then 28-day cycles
===References===
#DUO-E: Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT04269200
==Carboplatin & Paclitaxel (CP) & Pembrolizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Eskander et al. 2023 (NRG GY018)	2019-07 to 2022-12 	Phase 3 (E-RT-esc)	CP 	Longer PFS1 (co-primary endpoint)PFS12: 74% vs 38%(HR 0.30, 95% CI 0.19-0.48)Longer PFS2 (co-primary endpoint)Median PFS: 13.1 vs 8.7 mo(HR 0.54, 95% CI 0.41-0.71)
1Reported efficacy is for the dMMR cohort.
2Reported efficacy is for the pMMR cohort.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 5 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
====Immunotherapy====
*Pembrolizumab (Keytruda) as follows:
**Cycles 1 to 6: 200 mg IV over 30 minutes once on day 1
**Cycles 7 to 20: 400 mg IV over 30 minutes once on day 1
21-day cycle for 6 cycles, then 42-day cycle for 14 cycles
===References===
#NRG GY018: Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel R, Shahin MS, Cantuaria GH, Girda E, Mathews C, Kavecansky J, Leath CA 3rd, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Al Baghdadi T, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2159-2170. Epub 2023 Mar 27. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03914612
==Carboplatin & Paclitaxel (CP) & Trastuzumab==
CP+T: Carboplatin, Paclitaxel, Trastuzumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Fader et al. 2018	2011-2017 	Randomized Phase 2 (E-esc)	CP 	Longer PFS1 (primary endpoint)Median PFS: 12.9 vs 8 mo(HR 0.46, 90% CI 0.28-0.76)
1Reported efficacy is based on the 2020 update.
====Biomarker eligibility criteria====
*HER2 overexpression
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 5 IV 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====
*Trastuzumab (Herceptin) as follows:
**Cycle 1: 8 mg/kg IV once on day 1
**Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
===References===
#Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J Clin Oncol. 2018 Jul 10;36(20):2044-2051. Epub 2018 Mar 27. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01367002
##Update: Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clin Cancer Res. 2020 Aug 1;26(15):3928-3935. Epub 2020 Jun 29. link to original article link to PMC article EuroPMC
==Carboplatin & Pegylated liposomal doxorubicin==
===Regimen===
Study 	Dates of enrollment	Evidence
Pignata et al. 2007 (END-1)	2002-2005 	Phase 2
Note: All patients received 3 cycles of therapy. If there was no unacceptable toxicity, patients with stable or responsive disease received an additional 3 cycles.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given first
*Pegylated liposomal doxorubicin (Doxil) 40 mg/m2 IV over 60 minutes once on day 1, given second
28-day cycle for 3 to 6 cycles
====Dose and schedule modifications====
*G-CSF were not recommended for prophylaxis, but were allowed for grade 4 neutropenia
===References===
# END-1: Pignata S, Scambia G, Pisano C, Breda E, Di Maio M, Greggi S, Ferrandina G, Lorusso D, Zagonel V, Febbraro A, Riva N, De Rosa V, Gallo C, Perrone F; Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies Group. A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. Br J Cancer. 2007 Jun 4;96(11):1639-43. Epub 2007 May 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==Cisplatin & Doxorubicin==
AP: Adriamycin (Doxorubicin) & Platinol (Cisplatin)
===Regimen variant #1, 50/45===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fleming et al. 2004a (GOG 177)	1998-2000 	Phase 3 (C)	Cisplatin, Doxorubicin, Paclitaxel	Seems to have shorter OSMedian OS: 12.3 vs 15.3 mo(HR 1.33, 95% CI 1.01-1.75)
Note: body surface area was capped at 2 m2. This dosage was for patients with previous pelvic radiation or who were greater than 65 years old.
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 (maximum dose of 100 mg) IV over 60 minutes once on day 1, given second
*Doxorubicin (Adriamycin) 45 mg/m2 (maximum dose of 90 mg) IV once on day 1, given first
21-day cycle for 7 cycles
===Regimen variant #2, 50/60, capped BSA===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fleming et al. 2004a (GOG 177)	1998-2000 	Phase 3 (C)	Cisplatin, Doxorubicin, Paclitaxel	Seems to have shorter OSMedian OS: 12.3 vs 15.3 mo(HR 1.33, 95% CI 1.01-1.75)
Note: body surface area was capped at 2 m2.
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 (maximum dose of 100 mg) IV over 60 minutes once on day 1, given second
*Doxorubicin (Adriamycin) 60 mg/m2 (maximum dose of 120 mg) IV once on day 1, given first
21-day cycle for 7 cycles
===Regimen variant #3, 50/60, no cap on BSA===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fleming et al. 2004 (GOG 163)	1996-1998 	Phase 3 (C) 	Doxorubicin & Paclitaxel	Did not meet primary endpoint of ORR
Thigpen et al. 2004 (GOG 107)	Not reported 	Phase 3 (E-esc)	Doxorubicin 	Longer PFS (secondary endpoint)Median PFS: 5.7 vs 3.8 mo(HR 0.74, 95% CI 0.58-0.94)Higher ORR (primary endpoint)ORR: 42% vs 25%
Note: GOG 107 allowed up to a maximum cumulative doxorubicin dose of 500 mg/m2.
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1, given second
*Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1, given first
====Supportive therapy====
*Normal saline at 500 mL/H for 2 hours prior to and after cisplatin
21-day cycle for varying durations: 7 cycles (GOG 163); 8 cycles (GOG 107)
===Regimen variant #4, 60/60===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Gallion et al. 2003 (GOG 139)	1993-1996 	Phase 3 (C)	Cisplatin & Doxorubicin; chronomodulated	Did not meet primary endpoint of ORR
====Chemotherapy====
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles
===References===
# GOG 139: Gallion HH, Brunetto VL, Cibull M, Lentz SS, Reid G, Soper JT, Burger RA, Andersen W; Gynecologic Oncology Group. Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Oct 15;21(20):3808-13. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# GOG 177: Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Jun 1;22(11):2159-66. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003691
# GOG 163: Fleming GF, Filiaci VL, Bentley RC, Herzog T, Sorosky J, Vaccarello L, Gallion H. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol. 2004 Aug;15(8):1173-8. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# GOG 107: Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Oct 1;22(19):3902-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin, Doxorubicin, Paclitaxel==
TAP: Taxol (Paclitaxel), Adriamycin (Doxorubicin), Platinol (Cisplatin)
CDP: Cisplatin, Doxorubicin, Paclitaxel
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Fleming et al. 2004 (GOG 177)	1998-2000 	Phase 3 (E-esc)	Cisplatin & Doxorubicin	Seems to have longer OS (primary endpoint)Median OS: 15.3 vs 12.3 mo(HR 0.75, 95% CI 0.57-0.99)
Miller et al. 2020 (GOG0209) 	2003-2009 	Phase 3 (C) 	TC 	Non-inferior OSMedian OS: 41 vs 37 mo(HR 0.998, 90% CI 0.89-1.11)
Note: in GOG 177, body surface area was capped at 2 m2.
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once on day 1, given second
*Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1, given first
*Paclitaxel (Taxol) 160 mg/m2 IV over 3 hours once on day 2
====Supportive therapy====
*Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 3 to 12
21-day cycle for 7 cycles
===References===
# GOG 177: Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Jun 1;22(11):2159-66. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003691
# GOG0209: Miller DS, Filiaci VL, Mannel RS, Cohn DE, Matsumoto T, Tewari KS, DiSilvestro P, Pearl ML, Argenta PA, Powell MA, Zweizig SL, Warshal DP, Hanjani P, Carney ME, Huang H, Cella D, Zaino R, Fleming GF. Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209). J Clin Oncol. 2020 Nov 20;38(33):3841-3850. Epub 2020 Sep 29. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00063999
==Cisplatin & Ifosfamide==
CIM: Cisplatin, Ifosfamide, Mesna
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Sutton et al. 2000 (GOG 108)	1989-1996 	Phase 3 (E-esc)	Ifosfamide	Seems to have longer PFS (co-primary endpoint)Median PFS: 6 vs 4 mo(HR 0.73, 95% CI 0.56-0.95)
Note: This was the schedule after a mid-protocol amendment for excess toxicity.
====Chemotherapy====
*Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
*Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 4
====Supportive therapy====
*Mesna (Mesnex) 1500 mg/m2 IV once per day on days 1 to 4
21-day cycle for 8 cycles
===References===
# GOG 108: Sutton G, Brunetto VL, Kilgore L, Soper JT, McGehee R, Olt G, Lentz SS, Sorosky J, Hsiu JG. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group study. Gynecol Oncol. 2000 Nov;79(2):147-53. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin & Paclitaxel (TP)==
===Regimen variant #1, 50/175===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wu et al. 2024 (COMPASSION-16)	2021-09-11 to 2022-06-23	Phase 3 (C)	1a. CP & Cadonilimab1b. CP, Bevacizumab, Cadonilimab1c. TP & Cadonilimab1d. TP, Bevacizumab, Cadonilimab	Shorter OS (co-primary endpoint)Median OS: 22.8 vs NYR mo(HR 1.56, 95% CI 1.16-2.08)Shorter PFS (co-primary endpoint)Median PFS: 8.1 vs 12.7 mo(HR 1.61, 95% CI 1.25-2.04)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 6 cycles
===Regimen variant #2, 75/175===
Study 	Dates of enrollment	Evidence
Dimopoulos et al. 2000	1995-06 to 1997-05 	Phase 2
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV over 2 hours once on day 1, given second
*Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV or PO for two doses on day 1; 12 and 6 hours prior to paclitaxel
*Diphenhydramine (Benadryl) 25 mg IV once on day 1; 30 minutes prior to paclitaxel
*Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
*900 mL normal saline mixed with 100 mL mannitol given over 1 hour prior to cisplatin
*2 liters NS with potassium & magnesium after cisplatin
*"Appropriate antiemetics"
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 5 and continuing until WBC greater than 10,000 x 109/L
21-day cycle for up to 6 cycles
===References===
# Dimopoulos MA, Papadimitriou CA, Georgoulias V, Moulopoulos LA, Aravantinos G, Gika D, Karpathios S, Stamatelopoulos S. Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study. Gynecol Oncol. 2000 Jul;78(1):52-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#COMPASSION-13: Lou H, Cai H, Huang X, Li G, Wang L, Liu F, Qin W, Liu T, Liu W, Wang ZM, Li B, Xia Y, Wang J. Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study. Clin Cancer Res. 2024 Apr 15;30(8):1501-1508. link to original article link to PMC article EuroPMC NCT04868708
#COMPASSION-16: Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, Liao S, Ye Y, Yan P, Tang Q, Sun G, Liu T, Lu D, Hu M, Wang ZM, Li B, Xia M. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet. 2024 Oct 26;404(10463):1668-1676. Epub 2024 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04982237
==Cisplatin & Paclitaxel (TP) & Bevacizumab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wu et al. 2024 (COMPASSION-16)	2021-09-11 to 2022-06-23	Phase 3 (C)	1a. CP & Cadonilimab1b. CP, Bevacizumab, Cadonilimab1c. TP & Cadonilimab1d. TP, Bevacizumab, Cadonilimab	Shorter OS (co-primary endpoint)Median OS: 22.8 vs NYR mo(HR 1.56, 95% CI 1.16-2.08)Shorter PFS (co-primary endpoint)Median PFS: 8.1 vs 12.7 mo(HR 1.61, 95% CI 1.25-2.04)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 6: 50 mg/m2 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
===References===
#COMPASSION-13: Lou H, Cai H, Huang X, Li G, Wang L, Liu F, Qin W, Liu T, Liu W, Wang ZM, Li B, Xia Y, Wang J. Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study. Clin Cancer Res. 2024 Apr 15;30(8):1501-1508. link to original article link to PMC article EuroPMC NCT04868708
#COMPASSION-16: Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, Liao S, Ye Y, Yan P, Tang Q, Sun G, Liu T, Lu D, Hu M, Wang ZM, Li B, Xia M. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet. 2024 Oct 26;404(10463):1668-1676. Epub 2024 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04982237
==Cisplatin & Paclitaxel (TP), Bevacizumab, Cadonilimab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wu et al. 2024 (COMPASSION-16)	2021-09-11 to 2022-06-23	Phase 3 (E-esc)	1a. CP1b. CP & Bevacizumab1c. TP1d. TP & Bevacizumab	Longer OS (co-primary endpoint)Median OS: NYR vs 22.8 mo(HR 0.64, 95% CI 0.48-0.86)Longer PFS (co-primary endpoint)Median PFS: 12.7 vs 8.1 mo(HR 0.62, 95% CI 0.49-0.80)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 6: 50 mg/m2 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Targeted therapy====
*Bevacizumab (Avastin) 15 mg/kg IV once on day 1
====Immunotherapy====
*Cadonilimab (AK-104) 10 mg/kg IV once on day 1
21-day cycles
===References===
#COMPASSION-13: Lou H, Cai H, Huang X, Li G, Wang L, Liu F, Qin W, Liu T, Liu W, Wang ZM, Li B, Xia Y, Wang J. Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study. Clin Cancer Res. 2024 Apr 15;30(8):1501-1508. link to original article link to PMC article EuroPMC NCT04868708
#COMPASSION-16: Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, Liao S, Ye Y, Yan P, Tang Q, Sun G, Liu T, Lu D, Hu M, Wang ZM, Li B, Xia M. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet. 2024 Oct 26;404(10463):1668-1676. Epub 2024 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04982237
==Cisplatin & Paclitaxel (TP) & Cadonilimab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wu et al. 2024 (COMPASSION-16)	2021-09-11 to 2022-06-23	Phase 3 (E-esc)	1a. CP1b. CP & Bevacizumab1c. TP1d. TP & Bevacizumab	Longer OS (co-primary endpoint)Median OS: NYR vs 22.8 mo(HR 0.64, 95% CI 0.48-0.86)Longer PFS (co-primary endpoint)Median PFS: 12.7 vs 8.1 mo(HR 0.62, 95% CI 0.49-0.80)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 6: 50 mg/m2 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Cadonilimab (AK-104) 10 mg/kg IV once on day 1
21-day cycles
===References===
#COMPASSION-13: Lou H, Cai H, Huang X, Li G, Wang L, Liu F, Qin W, Liu T, Liu W, Wang ZM, Li B, Xia Y, Wang J. Cadonilimab Combined with Chemotherapy with or without Bevacizumab as First-Line Treatment in Recurrent or Metastatic Cervical Cancer (COMPASSION-13): A Phase 2 Study. Clin Cancer Res. 2024 Apr 15;30(8):1501-1508. link to original article link to PMC article EuroPMC NCT04868708
#COMPASSION-16: Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, Liao S, Ye Y, Yan P, Tang Q, Sun G, Liu T, Lu D, Hu M, Wang ZM, Li B, Xia M. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China. Lancet. 2024 Oct 26;404(10463):1668-1676. Epub 2024 Oct 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04982237
==Dactinomycin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Moore et al. 1999	1996 	Phase 2
====Chemotherapy====
*Dactinomycin (Cosmegen) 2 mg/m2 IV over 15 minutes once on day 1
28-day cycles
===References===
# Moore DH, Blessing JA, Dunton C, Buller RE, Reid GC; Gynecologic Oncology Group. Dactinomycin in the treatment of recurrent or persistent endometrial carcinoma: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 1999 Dec;75(3):473-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Dostarlimab monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Oaknin et al. 2020 (GARNETendometrial)	2017-2019 	Phase 1, >20 pts in this cohort (RT)
====Immunotherapy====
*Dostarlimab (Jemperli) as follows:
**Cycles 1 to 4: 500 mg IV over 30 minutes once on day 1
**Cycle 5 onwards: 1000 mg IV over 30 minutes once on day 1
21-day cycle for 4 cycles, then 42-day cycles
===References===
#GARNETendometrial: Oaknin A, Tinker AV, Gilbert L, Samouëlian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, Banerjee S, Guo W, Danaee H, Im E, Sabatier R. Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):1766-1772. Epub 2020 Oct 1. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02715284
##Update: Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, Sabatier R, O'Malley DM, Samouelian V, Boni V, Duska L, Ghamande S, Ghatage P, Kristeleit R, Leath C III, Guo W, Im E, Zildjian S, Han X, Duan T, Veneris J, Pothuri B. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022 Jan;10(1):e003777. link to original article link to PMC article EuroPMC
##PRO analysis: Kristeleit R, Mathews C, Redondo A, Boklage S, Hanlon J, Im E, Brown J. Patient-reported outcomes in the GARNET trial in patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer treated with dostarlimab. Int J Gynecol Cancer. 2022 Aug 16;32(10):1250–7. link to original article link to PMC article EuroPMC
==Doxorubicin monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Thigpen et al. 1979 	Not reported 	Phase 2 	 	
Omura et al. 1983 (GOG 21) 	1973-1979 	Randomized (C)	Dacarbazine & Doxorubicin 	Did not meet primary endpoint of ORR
Muss et al. 1985 (GOG 42) 	1979-1982 	Phase 3 (C) 	Cyclophosphamide & Doxorubicin (AC)	Did not meet efficacy endpoints
Thigpen et al. 1994 (GOG 48) 	1979-1985 	Randomized (C)	Cyclophosphamide & Doxorubicin (AC)	Did not meet efficacy endpoints
Aapro et al. 2003 (EORTC 55872) 	1988-1994 	Phase 2/3 (C) 	Cisplatin & Doxorubicin 	Seems to have shorter OS (primary endpoint)Median OS: 7 vs 9 mo(aHR 1.46, 95% CI 1.05-2.03)
Thigpen et al. 2004 (GOG 107) 	Not reported 	Phase 3 (C) 	Cisplatin & Doxorubicin 	Shorter PFS (secondary endpoint)Median PFS: 3.8 vs 5.7 mo(HR 1.35, 95% CI 1.06-1.72)Lower ORR (primary endpoint)ORR: 25% vs 42%
Makker et al. 2022 (KEYNOTE-775)	2018-2020 	Phase 3 (C) 	Lenvatinib & Pembrolizumab 	Shorter OS1Median OS: 11.4 vs 18.3 mo(HR 1.61, 95% CI 1.33-1.96)
1Reported efficacy for KEYNOTE-775 is for the overall population.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Doxorubicin (Adriamycin) 60 mg/m2 IV over 60 minutes once on day 1
21-day cycle for varying durations: 7 cycles (EORTC 55872); 8 cycles (all others)
===References===
# Thigpen JT, Buchsbaum HJ, Mangan C, Blessing JA; Gynecologic Oncology Group. Phase II trial of adriamycin in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Cancer Treat Rep. 1979 Jan;63(1):21-7. EuroPMC
# GOG 21: Omura GA, Major FJ, Blessing JA, Sedlacek TV, Thigpen JT, Creasman WT, Zaino RJ. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer. 1983 Aug 15;52(4):626-32. link to original article EuroPMC
# GOG 42: Muss HB, Bundy B, DiSaia PJ, Homesley HD, Fowler WC Jr, Creasman W, Yordan E. Treatment of recurrent or advanced uterine sarcoma: a randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer. 1985 Apr 15;55(8):1648-53. link to original article EuroPMC
# GOG 48: Thigpen JT, Blessing JA, DiSaia PJ, Yordan E, Carson LF, Evers C. A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1994 Jul;12(7):1408-14. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# EORTC 55872: Aapro MS, van Wijk FH, Bolis G, Chevallier B, van der Burg ME, Poveda A, Freire de Oliveira C, Tumolo S, Scotto di Palumbo V, Piccart M, Franchi M, Zanaboni F, Lacave AJ, Fontanelli R, Favalli G, Zola P, Guastalla JP, Rosso R, Marth C, Nooij M, Presti M, Scarabelli C, Splinter TA, Ploch E, Beex LV, ten Bokkel Huinink W, Forni M, Melpignano M, Blake P, Kerbrat P, Mendiola C, Cervantes A, Goupil A, Harper PG, Madronal C, Namer M, Scarfone G, Stoot JE, Teodorovic I, Coens C, Vergote I, Vermorken JB; EORTC Gynaecological Cancer Group. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol. 2003 Mar;14(3):441-8. Erratum in: Ann Oncol. 2003 May;14(5):811. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GOG 107: Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Oct 1;22(19):3902-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# KEYNOTE-775: Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03517449
##HRQoL analysis: Lorusso D, Colombo N, Herraez AC, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay SE, Ray-Coquard IL, Shapira-Frommer R, Kim YM, McCormack M, Massaad R, Nguyen AM, Zhao Q, McKenzie J, Prabhu VS, Makker V. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice. Eur J Cancer. 2023 Jun;186:172-184. Epub 2023 Mar 23. link to original article link to PMC article EuroPMC
##Update: Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. link to original article link to PMC article EuroPMC
==Ifosfamide monotherapy==
===Regimen variant #1, 1200 mg/m2 (3 days/cycle)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Homesley et al. 2007 (GOG 161)	1997-2004 	Phase 3 (C)	Ifosfamide & Paclitaxel	Seems to have shorter OSMedian OS: 8.4 vs 13.5 mo(HR 1.45, 95% CI 1.03-2.04)
Note: GOG 161 specifies that PO Mesna (Mesnex) is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references. This dosage is intended for patients with previous radiation.
====Chemotherapy====
*Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 3 
====Supportive therapy====
*Mesna (Mesnex) by the following route-based criteria:
**IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m2)
**PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL
21-day cycle for 8 cycles
===Regimen variant #2, 1500 mg/m2 (5 days/cycle)===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Sutton et al. 2000 (GOG 108)	1989-1996 	Phase 3 (C)	CIM 	Seems to have shorter PFS (co-primary endpoint)Median PFS: 4 vs 6 mo(HR 1.37, 95% CI 1.05-1.79)
====Chemotherapy====
*Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 1 to 5 
====Supportive therapy====
*Mesna (Mesnex) 1500 mg/m2 IV once per day on days 1 to 5
21-day cycle for 8 cycles
===Regimen variant #3, 1600 mg/m2 (3 days/cycle)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Homesley et al. 2007 (GOG 161)	1997-2004 	Phase 3 (C)	Ifosfamide & Paclitaxel	Seems to have shorter OSMedian OS: 8.4 vs 13.5 mo(HR 1.45, 95% CI 1.03-2.04)
Note: GOG 161 specifies that PO Mesna (Mesnex) is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references.
====Chemotherapy====
*Ifosfamide (Ifex) by the following exposure-based criteria:
**No previous radiation: 1600 mg/m2 IV once per day on days 1 to 3
**Previous radiation: 1200 mg/m2 IV once per day on days 1 to 3 
====Supportive therapy====
*Mesna (Mesnex) by the following route-based criteria:
**IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m2)
**PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL
21-day cycle for 8 cycles
===References===
# GOG 108: Sutton G, Brunetto VL, Kilgore L, Soper JT, McGehee R, Olt G, Lentz SS, Sorosky J, Hsiu JG. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group study. Gynecol Oncol. 2000 Nov;79(2):147-53. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# GOG 161: Homesley HD, Filiaci V, Markman M, Bitterman P, Eaton L, Kilgore LC, Monk BJ, Ueland FR; Gynecologic Oncology Group. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Feb 10;25(5):526-31. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003128
==Ifosfamide & Paclitaxel==
PI: Paclitaxel & Ifosfamide
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Homesley et al. 2007 (GOG 161)	1997-2004 	Phase 3 (E-esc)	Ifosfamide 	Seems to have longer OS (primary endpoint)Median OS: 13.5 vs 8.4 mo(HR 0.69, 95% CI 0.49-0.97)
Powell et al. 2022 (GOG-0261) 	2009-2014 	Phase 3 (C) 	Carboplatin & Paclitaxel	Non-inferior OSMedian OS: 29 vs 37 mo(HR 1.15, 90% CI 0.93-1.43)
Note: GOG 161 specifies that PO Mesna (Mesnex) is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references. Treatment was given for 8 cycles in GOG 161.
====Chemotherapy====
*Ifosfamide (Ifex) by the following exposure-based criteria:
**No previous radiation: 1600 mg/m2 IV once per day on days 1 to 3
**Previous radiation: 1200 mg/m2 IV once per day on days 1 to 3 
*Paclitaxel (Taxol) 135 mg/m2 IV over 3 hours once on day 1
====Supportive therapy====
Per GOG 161:
*Mesna (Mesnex) by the following route-based criteria:
**IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m2)
**PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL
*Dexamethasone (Decadron) 20 mg IV or PO for two doses on day 1; 12 and 6 hours prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
*One of the following H2 blockers:
**Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
**Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
21-day cycle for 6 to 10 cycles
===References===
# GOG 161: Homesley HD, Filiaci V, Markman M, Bitterman P, Eaton L, Kilgore LC, Monk BJ, Ueland FR; Gynecologic Oncology Group. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Feb 10;25(5):526-31. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003128
# GOG-0261: Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J Clin Oncol. 2022 Mar 20;40(9):968-977. Epub 2022 Jan 10. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00954174
==Lenvatinib & Pembrolizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Makker et al. 2019 (KEYNOTE-146)	2015-2017 	Phase 2 (RT) 	 	
Makker et al. 2022 (KEYNOTE-775)	2018-2020 	Phase 3 (E-RT-switch-ooc)	Investigator's choice of:1a. Doxorubicin1b. Paclitaxel	Longer OS1 (co-primary endpoint)Median OS: 18.3 vs 11.4 mo(HR 0.62, 95% CI 0.51-0.75)
1Reported efficacy is for the overall population.
====Targeted therapy====
*Lenvatinib (Lenvima) 20 mg PO once per day on days 1 to 21
====Immunotherapy====
*Pembrolizumab (Keytruda) as follows:
**Cycle 1 up to 35: 200 mg IV over 30 minutes once on day 1
21-day cycles
===References===
# KEYNOTE-146: Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, Di Simone C, Hyman DM, Stepan DE, Dutcus CE, Schmidt EV, Guo M, Sachdev P, Shumaker R, Aghajanian C, Taylor M. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):711-718. Epub 2019 Mar 25. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT02501096
##Update: Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, Romeo M, Bratos R, Brose MS, DiSimone C, Messing M, Stepan DE, Dutcus CE, Wu J, Schmidt EV, Orlowski R, Sachdev P, Shumaker R, Casado Herraez A. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. J Clin Oncol. 2020 Sep 10;38(26):2981-2992. Epub 2020 Mar 13. link to original article link to PMC article EuroPMC
# KEYNOTE-775: Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03517449
##HRQoL analysis: Lorusso D, Colombo N, Herraez AC, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay SE, Ray-Coquard IL, Shapira-Frommer R, Kim YM, McCormack M, Massaad R, Nguyen AM, Zhao Q, McKenzie J, Prabhu VS, Makker V. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice. Eur J Cancer. 2023 Jun;186:172-184. Epub 2023 Mar 23. link to original article link to PMC article EuroPMC
##Update: Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. link to original article link to PMC article EuroPMC
==Paclitaxel monotherapy==
===Regimen variant #1, 80 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Makker et al. 2022 (KEYNOTE-775)	2018-2020 	Phase 3 (C)	Lenvatinib & Pembrolizumab	Shorter OS1Median OS: 11.4 vs 18.3 mo(HR 1.61, 95% CI 1.33-1.96)
1Reported efficacy is for the overall population.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
28-day cycles
===Regimen variant #2, 175 mg/m2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lissoni et al. 1996 	1993-1995 	Phase 2 	 	
Lincoln et al. 2003 	1994-1996 	Phase 2 	 	
McMeekin et al. 2015 (IXAMPLE2)	2009-2012 	Phase 3 (C)	Ixabepilone	Seems to have longer OS (primary endpoint)Median OS: 12.3 vs 10.9 mo(HR 0.77, 95% CI 0.59-1.00)
Note: in Lincoln et al. 2003, this was the dosage for patients with previous pelvic radiation.
====Chemotherapy====
*Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
====Supportive therapy====
*Hydrocortisone (Cortef) 250 mg IV once on day 1; 60 minutes prior to paclitaxel
*Chlorpheniramine (Chlor-Trimeton) 10 mg IM once on day 1; 60 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to paclitaxel
21-day cycles
===Regimen variant #3, 200 mg/m2===
Study 	Dates of enrollment	Evidence
Lincoln et al. 2003	1994-1996 	Phase 2
====Chemotherapy====
*Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV or PO for 2 doses on day 1; 12 and 6 hours prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV or PO once on day 1; 30 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
21-day cycles
====Dose and schedule modifications====
*Paclitaxel dose can be changed to 135 or 110 mg/m2 depending on toxicity
===Regimen variant #4, continuous infusion===
Study 	Evidence
Ball et al. 1996	Phase 2
====Chemotherapy====
*Paclitaxel (Taxol) by the following exposure-based criteria:
**No prior pelvic radiation: 250 mg/m2 IV continuous infusion over 24 hours, started on day 1
**Previous pelvic radiation: 200 mg/m2 IV continuous infusion over 24 hours, started on day 1
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV or PO for 2 doses on day 1; 12 and 6 hours prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV or PO once on day 1; 30 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 3, 24 hours after paclitaxel, continued for at least 12 days or until two successive total leukocyte counts are 10,000 or greater, whichever comes last
21-day cycles
====Dose and schedule modifications====
*Paclitaxel dose can be changed to 200, 170, 135, 110 mg/m2 depending on toxicity
===References===
# Ball HG, Blessing JA, Lentz SS, Mutch DG; Gynecologic Oncology Group. A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. 1996 Aug;62(2):278-81. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Lissoni A, Zanetta G, Losa G, Gabriele A, Parma G, Mangioni C. Phase II study of paclitaxel as salvage treatment in advanced endometrial cancer. Ann Oncol. 1996 Oct;7(8):861-3. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Lincoln S, Blessing JA, Lee RB, Rocereto TF; Gynecologic Oncology Group. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Mar;88(3):277-81. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# IXAMPLE2: McMeekin S, Dizon D, Barter J, Scambia G, Manzyuk L, Lisyanskaya A, Oaknin A, Ringuette S, Mukhopadhyay P, Rosenberg J, Vergote I. Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. Gynecol Oncol. 2015 Jul;138(1):18-23. Epub 2015 Apr 26. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT00883116
# KEYNOTE-775: Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03517449
##HRQoL analysis: Lorusso D, Colombo N, Herraez AC, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay SE, Ray-Coquard IL, Shapira-Frommer R, Kim YM, McCormack M, Massaad R, Nguyen AM, Zhao Q, McKenzie J, Prabhu VS, Makker V. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice. Eur J Cancer. 2023 Jun;186:172-184. Epub 2023 Mar 23. link to original article link to PMC article EuroPMC
##Update: Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. link to original article link to PMC article EuroPMC
==Pembrolizumab monotherapy==
===Regimen variant #1, bi-weekly===
Study 	Dates of enrollment	Evidence
Le et al. 2015 (KEYNOTE-016) 	2013-09 to 2016-09 	Phase 2, fewer than 20 pts of this subtype
Ott et al. 2017b (KEYNOTE-028endometrial)	Not reported 	Phase 1b
Note: KEYNOTE-016 was an expansion to a CRC-specific trial.
====Immunotherapy====
*Pembrolizumab (Keytruda) 10 mg/kg IV over 30 minutes once on day 1
14-day cycle for varying durations: 52 cycles (KEYNOTE-028endometrial); indefinitely (KEYNOTE-016)
===Regimen variant #2, q3wk===
Study 	Dates of enrollment	Evidence
O'Malley et al. 2022 (KEYNOTE-158endometrial)	2016-2020 	Phase 2 (RT)
Note: KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.
====Biomarker eligibility criteria====
*Cohort K: MSI-H/dMMR endometrial cancer
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===References===
# KEYNOTE-028endometrial: Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, Puzanov I, Mehnert JM, Aung KL, Lopez J, Carrigan M, Saraf S, Chen M, Soria JC. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol. 2017 Aug 1;35(22):2535-2541. Epub 2017 May 10. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02054806
# KEYNOTE-016: Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. Epub 2015 May 30. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT01876511
## Update: Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8. link to original article link to PMC article EuroPMC
# KEYNOTE-158endometrial: O'Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus Acosta A, Miller WH Jr, Safra T, Italiano A, Mileshkin L, Xu L, Jin F, Norwood K, Maio M. Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. J Clin Oncol. 2022 Mar 1;40(7):752-761. Epub 2022 Jan 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02628067
==Temsirolimus monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Oza et al. 2011 (NCIC IND.160)	2004-2007 	Phase 2
====Targeted therapy====
*Temsirolimus (Torisel) 25 mg IV over 30 minutes once on day 1
7-day cycles
===References===
# NCIC IND.160: Oza AM, Elit L, Tsao MS, Kamel-Reid S, Biagi J, Provencher DM, Gotlieb WH, Hoskins PJ, Ghatage P, Tonkin KS, Mackay HJ, Mazurka J, Sederias J, Ivy P, Dancey JE, Eisenhauer EA; NCIC Clinical Trials Group. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011 Aug 20;29(24):3278-85. Epub 2011 Jul 25. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00072176
==Topotecan monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Wadler et al. 2003 (ECOG E3E93)	1995 to not reported	Phase 2
====Chemotherapy====
*Topotecan (Hycamtin) by the following exposure-based criteria:
**No prior pelvic radiation: 1.5 mg/m2 IV once per day on days 1 to 5
**Previous pelvic radiation: 1.2 mg/m2 IV once per day on days 1 to 5
21-day cycles
====Dose and schedule modifications====
*Topotecan dosage for patients with previous pelvic radiation can be increased to the 1.5 mg/m2 dose in later cycles if there are no toxicities higher than grade 1
===References===
# ECOG E3E93: Wadler S, Levy DE, Lincoln ST, Soori GS, Schink JC, Goldberg G. Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern Cooperative Oncology Group Study E3E93. J Clin Oncol. 2003 Jun 1;21(11):2110-4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=Endocrine therapy for advanced, recurrent, or metastatic disease=
==Anastrozole monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Rose et al. 2000	1997-05 to 1998-03 	Phase 2
====Endocrine therapy====
*Anastrozole (Arimidex) 1 mg PO once per day
Continued indefinitely
===References===
# Rose PG, Brunetto VL, VanLe L, Bell J, Walker JL, Lee RB; Gynecologic Oncology Group. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000 Aug;78(2):212-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Medroxyprogesterone acetate monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kelley & Baker 1961	1950-1959 	Non-randomized	 	
Thigpen et al. 1999	1985-1989 	Phase 3 (C) 	MPA; high-dose	Did not meet primary endpoint of ORR
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Kelley & Baker 1961 examined a variety of progestins and is included for historic interest.
====Endocrine therapy====
*Medroxyprogesterone acetate (MPA) 200 mg PO once per day
Continued indefinitely
===References===
# Kelley RM, Baker WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961 Feb 2;264:216-22. link to original article EuroPMC
# Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, Soper JT, Given FT; Gynecologic Oncology Group. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999 Jun;17(6):1736-44. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Medroxyprogesterone acetate & Tamoxifen==
===Regimen===
Study 	Dates of enrollment	Evidence
Whitney et al. 2004	1991-06 to 1996-02 	Phase 2
====Endocrine therapy====
*Medroxyprogesterone acetate (MPA) 100 mg PO twice per day on days 8 to 14, 22 to 28 (even-numbered weeks)
*Tamoxifen (Nolvadex) 20 mg PO twice per day on days 1 to 28
28-day cycles
===References===
# Whitney CW, Brunetto VL, Zaino RJ, Lentz SS, Sorosky J, Armstrong DK, Lee RB; Gynecologic Oncology Group. Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Jan;92(1):4-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Megestrol monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kelley & Baker 1961 	1950-1959 	Non-randomized 	 	
Pandya et al. 2001 (ECOG E4882)	1982-1984 	Randomized Phase 2 (C)	Megestrol & Tamoxifen	Did not meet efficacy endpoints
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Kelley & Baker 1961 examined a variety of progestins and is included for historic interest.
====Endocrine therapy====
*Megestrol (Megace) 80 mg PO twice per day
Continued indefinitely
===References===
# Kelley RM, Baker WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961 Feb 2;264:216-22. link to original article EuroPMC
# ECOG E4882: Pandya KJ, Yeap BY, Weiner LM, Krook JE, Erban JK, Schinella RA, Davis TE. Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol. 2001 Feb;24(1):43-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Megestrol & Tamoxifen==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Pandya et al. 2001 (ECOG E4882)	1982-1984 	Randomized Phase 2 (E-switch-ic)	Megestrol 	Did not meet primary efficacy endpoints
Fiorica et al. 2004 	1994-1995 	Phase 2 	 	
====Endocrine therapy====
*Megestrol (Megace) as follows:
**Odd cycles: 80 mg PO twice per day on days 1 to 21
*Tamoxifen (Nolvadex) as follows:
**Even cycles: 20 mg PO twice per day on days 1 to 21
21-day cycles
===References===
# ECOG E4882: Pandya KJ, Yeap BY, Weiner LM, Krook JE, Erban JK, Schinella RA, Davis TE. Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol. 2001 Feb;24(1):43-6. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# Fiorica JV, Brunetto VL, Hanjani P, Lentz SS, Mannel R, Andersen W; Gynecologic Oncology Group. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Jan;92(1):10-4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Tamoxifen monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Quinn et al. 1989 	Not reported 	Phase 2
Thigpen et al. 2001 (GOG-81F)	1987-1991 	Phase 2
====Endocrine therapy====
*Tamoxifen (Nolvadex) 20 mg PO twice per day
Continued indefinitely
===References===
# Quinn MA, Campbell JJ. Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol. 1989 Jan;32(1):1-3. link to original article EuroPMC
# GOG-81F: Thigpen T, Brady MF, Homesley HD, Soper JT, Bell J. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Jan 15;19(2):364-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
Category:Endometrial cancer regimens
Category:Disease-specific pages
Category:Gynecologic cancers