Endometrial cancer

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 Alaina J. Brown, MD, MPH
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Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!

32 regimens on this page
51 variants on this page


Guidelines

ESMO

Older

NCCN

Older

Adjuvant therapy

Carboplatin & Paclitaxel (CP)

Regimen variant #1, 5/175 x 4

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

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles


Regimen variant #2, 6/175 x 6

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Matei et al. 2019 (GOG 258) 2009-2014 Phase 3 (C) Cisplatin & RT, then CP x 4 Did not meet primary endpoint of RFS

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 PubMed Clinical Trial Registry
    1. 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 contains dosing details in manuscript link to PMC article PubMed
  2. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry
  3. 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 contains dosing details in manuscript link to PMC article PubMed UMIN000000522
  4. KEYNOTE-B21: Clinical Trial Registry

CIM

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 superior OS1
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

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

  1. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry

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

Chemotherapy

Supportive therapy

21-day cycle for 6 cycles


Regimen variant #2, 50/60 x 6

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Nomura et al. 2019 (JGOG2043) 2006-2011 Phase 3 (C) 1. Carboplatin & Paclitaxel
2. Cisplatin & Docetaxel 		Did not meet primary endpoint of PFS

Preceding treatment

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #3, 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 Superior OS
OS60: 55% vs 42%
(aHR 0.68, 95% CI 0.52-0.89)

Preceding treatment

Chemotherapy

Supportive therapy

  • Normal saline at 500 mL/H for 2 hours prior to and after cisplatin

21-day cycle for 8 cycles

References

  1. 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 contains dosing details in manuscript PubMed
  2. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry
    1. 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 PubMed
  3. 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 contains dosing details in manuscript link to PMC article PubMed UMIN000000522

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

Chemotherapy

21-day cycle for 2 cycles

Radiotherapy

5.5-week course

Subsequent treatment

References

  1. 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 PubMed Clinical Trial Registry
    1. 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 contains dosing details in manuscript link to PMC article PubMed

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 Superior RFS
Maggi et al. 2006 1990-1997 Phase 3 (C) CAP Did not meet 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 RCT
de Boer et al. 2018 (PORTEC-3) 2006-2013 Phase 3 (C) Cisplatin & RT, then Carboplatin & Paclitaxel Seems to have inferior OS1

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

Radiotherapy

One course

Subsequent treatment

  • GOG 184: CD x 6 versus CDP x 6

References

  1. GOG 99: Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG; Gynecologic Oncology Group. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Mar;92(3):744-51. Erratum in: Gynecol Oncol. 2004 Jul;94(1):241-2. link to original article PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry
    1. 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 PubMed
  5. 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 PubMed Clinical Trial Registry
    1. 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 PubMed

Whole abdominal radiation (WAI)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Randall et al. 2006 (GOG 122) 1992-2000 Phase 3 (E-switch-ooc) Cisplatin & Doxorubicin Inferior OS
Wolfson et al. 2007 (GOG 150) 1993-2005 Phase 3 (C) CIM Might have inferior OS

Not commonly used but was a comparator arm; here for reference purposes only.

Radiotherapy

References

  1. 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 contains dosing details in manuscript PubMed
  2. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry

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

21-day cycles

References

  1. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry

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

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

28-day cycles

References

  1. 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 contains dosing details in manuscript PubMed

Carboplatin & Paclitaxel (CP)

Regimen variant #1, 5/175 x 6

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pectasides et al. 2008 2004-01 to 2007-09 Phase 2
Awaiting publication (RUBY) 2019-2022 Phase 3 (C) CP & Dostarlimab Inferior OS

Note: this is the lower limit of cycles in Pectasides et al. 2008.

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #2, 5/175 x 9

Study Dates of enrollment Evidence
Pectasides et al. 2008 2004-01 to 2007-09 Phase 2

Note: this is the upper limit of cycles in Pectasides et al. 2008.

Chemotherapy

21-day cycle for 9 cycles


Regimen variant #3, 5/175, indefinite

Study Dates of enrollment Evidence
Hoskins et al. 2001 1995-1998 Phase 2
Sorbe et al. 2007 2000-2004 Phase 2

Note: this is the lower limit of carboplatin dosing allowed in Hoskins et al. 2001.

Chemotherapy

21-day cycles


Regimen variant #4, 6/175 x 7

ESMO-preferred (I-A, 2016)
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Miller et al. 2020 (GOG0209) 2003-2009 Phase 3 (E-de-esc) TAP Non-inferior OS
Median OS: 37 vs 41 mo
(HR 1.002, 90% CI 0.9-1.12)

Note: ESMO recommends 6 cycles, whereas the cited RCT uses 7 cycles.

Chemotherapy

21-day cycle for 7 cycles


Regimen variant #5, 6/175 x 6-10

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Powell et al. 2022 (GOG-0261) 2009-2014 Phase 3 (E-switch-ic) Ifosfamide & Paclitaxel Non-inferior OS
Median OS: 37 vs 29 mo
(HR 0.87, 90% CI 0.70-1.075)

Chemotherapy

21-day cycle for 6 to 10 cycles


Regimen variant #6, 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

21-day cycles

References

  1. Hoskins PJ, Swenerton KD, Pike JA, Wong F, Lim P, Acquino-Parsons C, Lee 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 contains dosing details in manuscript PubMed
  2. 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 contains dosing details in manuscript PubMed
  3. 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 contains dosing details in manuscript PubMed content property of HemOnc.org
  4. 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 PubMed
  5. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry
  6. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry
  7. RUBY: Clinical Trial Registry

Carboplatin & Paclitaxel (CP) & Dostarlimab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (RUBY) 2019-2022 Phase 3 (E-esc) CP Superior OS (co-primary endpoint)
OS24: 71.3% vs 56%
(HR 0.64, 95% CI 0.46-0.87)

Chemotherapy

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

  1. RUBY: Clinical Trial Registry

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 Superior PFS1
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

Targeted therapy

21-day cycles

References

  1. 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 contains dosing details in manuscript PubMed Clinical Trial Registry
    1. 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 (Clinical Trial Registry): 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 PubMed

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

28-day cycle for 3 to 6 cycles

Dose modifications

  • G-CSF were not recommended for prophylaxis, but were allowed for grade 4 neutropenia

References

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

CIM

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 superior PFS

Chemotherapy

Supportive therapy

References

  1. 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 PubMed

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 inferior OS

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

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 inferior OS

Note: body surface area was capped at 2 m2.

Chemotherapy

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) NR Phase 3 (E-esc) Doxorubicin Seems to have superior PFS

Chemotherapy

Supportive therapy

  • Normal saline at 500 mL/H for 2 hours prior to and after cisplatin

21-day cycle for up to 8 cycles


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

21-day cycle for up to 8 cycles

References

  1. 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 contains dosing details in abstract PubMed
  2. 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 contains dosing details in manuscript PubMed Clinical Trial Registry
  3. 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 contains dosing details in abstract PubMed
  4. 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 contains dosing details in abstract PubMed

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 superior OS
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 OS

Note: in GOG 177, body surface area was capped at 2 m2.

Chemotherapy

Supportive therapy

21-day cycle for 7 cycles

References

  1. 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 contains dosing details in manuscript PubMed Clinical Trial Registry
  2. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry

Cisplatin & Paclitaxel

Regimen

Study Dates of enrollment Evidence
Dimopoulos et al. 2000 1995-06 to 1997-05 Phase 2

Chemotherapy

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

  1. 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 contains dosing details in manuscript PubMed

Dactinomycin monotherapy

Regimen

Study Dates of enrollment Evidence
Moore et al. 1999 1996 Phase 2

Chemotherapy

28-day cycles

References

  1. 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 contains dosing details in manuscript PubMed

Dostarlimab monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Oaknin et al. 2020 (GARNET)
ESMO-MCBS (3)
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

  1. GARNET: 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 contains dosing details in manuscript PubMed Clinical Trial Registry
    1. 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 PubMed
    2. 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 PubMed

Doxorubicin monotherapy

Regimen variant #1, 7 cycles

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Aapro et al. 2003 (EORTC 55872) 1988-1994 Phase 3 (C) Cisplatin & Doxorubicin Might have inferior OS

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

28-day cycle for up to 7 cycles


Regimen variant #2, 8 cycles

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Thigpen et al. 1979 NR 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
Thigpen et al. 2004 (GOG 107) NR Phase 3 (C) Cisplatin & Doxorubicin Seems to have inferior PFS
Makker et al. 2022 (KEYNOTE-775) 2018-2020 Phase 3 (C) Lenvatinib & Pembrolizumab Inferior OS

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

21-day cycle for up to 8 cycles

References

  1. 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. PubMed
  2. 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 PubMed
  3. 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 PubMed
  4. 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 contains dosing details in abstract PubMed
  5. 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 contains dosing details in manuscript PubMed
  6. 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 contains dosing details in abstract PubMed
  7. 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 contains dosing details in manuscript PubMed Clinical Trial Registry

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 inferior OS

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

Supportive therapy

  • Mesna (Mesnex) 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)
    • Alternate 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 inferior PFS

Chemotherapy

Supportive therapy

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 inferior OS

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) 1600 mg/m2 IV once per day on days 1 to 3
    • Dosage for patients with previous radiation: 1200 mg/m2 IV once per day on days 1 to 3

Supportive therapy

  • Mesna (Mesnex) 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)
    • Alternate 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

  1. 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 contains dosing details in manuscript PubMed
  2. 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 contains dosing details in manuscript PubMed Clinical Trial Registry

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 superior OS
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 OS

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) 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)
    • Alternate 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:

21-day cycle for 6 to 10 cycles

References

  1. 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 contains dosing details in manuscript PubMed Clinical Trial Registry
  2. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry

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)
ESMO-MCBS (4)
2018-2020 Phase 3 (E-RT-switch-ooc) Investigator's choice of:
1a. Doxorubicin
1b. Paclitaxel 		Superior OS1
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

Immunotherapy

21-day cycles

References

  1. 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 contains dosing details in abstract PubMed Clinical Trial Registry
    1. 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 PubMed
  2. 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 contains dosing details in manuscript PubMed Clinical Trial Registry

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 Inferior OS

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

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 superior OS

Note: in Lincoln et al. 2003, this was the dosage for patients with previous pelvic radiation.

Chemotherapy

Supportive therapy

21-day cycles


Regimen variant #3, 200 mg/m2

Study Dates of enrollment Evidence
Ball et al. 1996 NR Phase 2
Lincoln et al. 2003 1994-1996 Phase 2

Note: in Ball et al. 1996, this was the dosage for patients with previous pelvic radiation.

Chemotherapy

  • Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
    • Ball et al. 1996 gave as a 24 hour continuous infusion
    • Dose can be changed to 135 or 110 mg/m2 depending on toxicity

Supportive therapy

21-day cycles


Regimen variant #4, 250 mg/m2

Study Evidence
Ball et al. 1996 Phase 2

Chemotherapy

  • Paclitaxel (Taxol) 250 mg/m2 IV continuous infusion over 24 hours, started on day 1
    • Dosage for patients with previous pelvic radiation: 200 mg/m2 IV continuous infusion over 24 hours, started on day 1
    • Dose can be changed to 200, 170, 135, 110 mg/m2 depending on toxicity

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

References

  1. 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 contains dosing details in manuscript PubMed
  2. 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 contains dosing details in manuscript PubMed
  3. 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 contains dosing details in manuscript PubMed
  4. 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 contains dosing details in abstract PubMed Clinical Trial Registry
  5. 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 contains dosing details in manuscript PubMed Clinical Trial Registry

Pembrolizumab monotherapy

Regimen variant #1, bi-weekly

Study Dates of enrollment Evidence
Le et al. 2015 (KEYNOTE-016) 2013-2016 Phase 2, <20 pts of this subtype
Ott et al. 2017b (KEYNOTE-028) NR Phase 1b

Note: KEYNOTE-016 was an expansion to a CRC-specific trial.

Immunotherapy

14-day cycle for up to 52 cycles (2 years)


Regimen variant #2, q3wk

Study Dates of enrollment Evidence
O'Malley et al. 2022 (KEYNOTE-158)
ESMO-MCBS (3)
2016-2020 Phase 2 (RT)

Biomarker eligibility criteria

  • Cohort K: MSI-H/dMMR endometrial cancer

Immunotherapy

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

References

  1. KEYNOTE-028: 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 contains dosing details in abstract PubMed Clinical Trial Registry
  2. 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 contains dosing details in abstract link to PMC article PubMed Clinical Trial Registry
    1. 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 contains dosing details in supplement PubMed
  3. KEYNOTE-158: 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 contains dosing details in abstract PubMed Clinical Trial Registry

Temsirolimus monotherapy

Regimen

Study Dates of enrollment Evidence
Oza et al. 2011 (NCIC IND.160) 2004-2007 Phase 2

Targeted therapy

28-day cycles

References

  1. 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 contains dosing details in manuscript link to PMC article PubMed Clinical Trial Registry

Topotecan monotherapy

Regimen

Study Dates of enrollment Evidence
Wadler et al. 2003 (ECOG E3E93) 1995-NR Phase 2

Chemotherapy

  • Topotecan (Hycamtin) 1.5 mg/m2 IV once per day on days 1 to 5
    • Dosage for patients with previous pelvic radiation: 1.2 mg/m2, which can be increased to the 1.5 mg/m2 dose in later cycles if there are no toxicities higher than grade 1

21-day cycles

References

  1. 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 contains dosing details in manuscript PubMed

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

Continued indefinitely

References

  1. 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 contains dosing details in manuscript PubMed

Medroxyprogesterone 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) Medroxyprogesterone; 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

Continued indefinitely

References

  1. 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 PubMed
  2. 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 contains dosing details in manuscript PubMed

Medroxyprogesterone & Tamoxifen

Regimen

Study Dates of enrollment Evidence
Whitney et al. 2004 1991-06 to 1996-02 Phase 2

Endocrine therapy

Continued indefinitely

References

  1. 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 contains dosing details in manuscript PubMed

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

Continued indefinitely

References

  1. 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 PubMed
  2. 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 contains dosing details in manuscript PubMed

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

21-day cycles

References

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

Tamoxifen monotherapy

Regimen

Study Dates of enrollment Evidence
Quinn et al. 1989 NR Phase 2
Thigpen et al. 2001 (GOG-81F) 1987-1991 Phase 2

Endocrine therapy

Continued indefinitely

References

  1. Quinn MA, Campbell JJ. Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol. 1989 Jan;32(1):1-3. link to original article PubMed
  2. 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 contains dosing details in manuscript PubMed
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