1. Endometrial Cancer Commitee Minutes Prague, 21 October 2010 David Miller, Ketta Lorusso

2. Endometrial Cancer Commitee Agenda Prague October 21, 2010 PROPOSED GCIG STUDIES FOR REVIEW STAGING LYTEC LYmphadenectomy Trial in Endometrial Cancer

3. Treatment Algorithm

4. Participating Institutions Endorsed by ENGOT 2/2010 AGO AustGROIN EORTC GCG ICORG BGOG MANGO GEICO MITO HECOG NCRI GINECO NOGGO NSGODGC JGOGKGOG TRSGO

5. Adjuvant Endometrial Cancer Trial Mansoor@rh.regionh.dk Five phase 3 trials will collaborate internationally to answer 4 major questions in the management of endometrial cancer: Does proper lymphadenectomy improve survival? LYTEC Trial & AGO-ECLAT trial Is there a need for adjuvant chemotherapy in node negative high-risk early stage patients? ENGOT-EN2-DGCG trial Is adjuvant chemo followed by RT better than chemo alone in high-risk nodal status unknown early stage or stage 3 patients? NSGO trial Can combination of standard chemotherapy with targeted therapy compared to combination chemotherapy alone improve disease control rate of advanced or chemo-naïve relapsed endometrial cancer? AGO/NOGGO trial

6. Clinically presumed: FIGO IB-II any histo type, FIGO I A G3 endometroid, FIGO IA/B histo type II FIGO III not Ro and pos. LN or cytology only; FIGO IV Recurrent FIGO I/II R Standard arm: Carbo-paclitaxel + Placebo Experim. arm: Carbo-paclitaxel + mTOR inhibitor surgery Bulky LN LNE N-N+ No bulky LN R In OP LNE*no LNE N- N+ R Chemo 1 Carbo-paclitaxel Chemo +. Radiotherapy R Chemo 1 Carbo-paclitaxel observation + extra LN disease without extra LN disease ENGOT-NESTEC: NE twork ST udy in E ndometrial C ancer under the ENGOT umbrella and in cooperation with the Mayo clinic. R Mayo trial (Dowdy, Mariani) AGO ECLAT trial (Emons) R NSGO trial (Hogberg) R AGO/NOGGO trial (Sehouli) R DGCG trial (Mirza)

7. Endometrial Cancer Commitee Agenda Prague October 21, 2010 NEW PROPOSAL: ENGOT-EN2-DGCG A phase III trial of postoperative chemotherapy or no further treatment for patients with node negative stage I-II intermediate or high risk endometrial cancer: Interested groups: AGO Germ, Belgian GOG, EORTC, MANGO

8. AFTER 4 NSGO Trial A phase III intergroup trial of adjuvant therapy in radically operated endometrial cancer patients with high risk for micro-metastatic disease: 4 courses of adjuvant CT followed by RT versus 2 more courses of CT Endometrial Cancer Commitee Agenda Prague October 21, 2010 NEW PROPOSAL:

9. Endometrial Cancer Commitee Agenda Prague October 21, 2010 PROPOSED GCIG STUDIES FOR REVIEW ADVANCED/RECURRENT GOG-0238 A randomized trial of Pelvic Irradiation with or without Concurrent Weekly Cisplatin in patients with pelvic-only recurrence of carcinoma of the uterine corpus. 25/164 Paricipating Group: RTOG Interested groups: NCRI, SWOG

10. GOG-0238

11. GOG0238 Objectives –PFS –Sites of recurrence –OS Stats –Phase II-III –Interim analysis > 60 failures –Opened Feb ‘08 –N = 25/164

12. Endometrial Cancer Commitee Agenda Prague October 21, 2010 ADVANCED/RECURRENT NCIC CTG EN8 Randomized Phase III trial on Progestational Hormone Therapy vs Deferolimus in women with recurrent or metastatic endometrial cancer Interested Groups: ACRIN, AGO-AUST, AGO-OVAR, ANZOG, Dutch GOG, EORTC, GEICO, GINECO, MANGO, MITO, JGOG, NCRI, NSGO, SWOG PROPOSED GCIG STUDIES FOR REVIEW

13. Schema Sample size: Approximately 460 patients Arm 2: medroxy progesterone 200 mg or megestrol 160 mg (as per local practice) po daily Chemotherapy options Survival follow-up Disease progression Imaging q 8 weeks Arm 1: ridaforolimus 40 mg po days 1-5 each week RANDOMIZERANDOMIZE Women with recurrent or metastatic endometrial cancer 1-2 Prior Chemotherapy

14. Endometrial Cancer Commitee Agenda Prague October 21, 2010 PROPOSED GCIG STUDIES FOR REVIEW TROPHOBLASTIC NEOPLASIA ANZGOG : 1. CHM with negative HCG 8 weeks post evacuation 2. PHM reaching negative HCG Cross registry analysis or randomized trial of current local policy FU vs discontinuation of FU according to the above findings. End point: comparison of incidence of persistent GTN in either arms. Follow up with ISSTD

15. Endometrial Cancer Commitee Agenda Prague October 21, 2010 PROPOSED GCIG STUDIES FOR REVIEW TROPHOBLASTIC NEOPLASIA GOG UC 1005 A sequential phase II/III randomized trial comparing 3 widely used regimens for the management of low risk Gestational Trophoblastic Neoplasia (John Tidy: john.tidy@sth.nhs.uk). Interested groups: AGO Aust., JGOG, MITOjohn.tidy@sth.nhs.uk

16. A randomized trial comparing three widely used regimens for the management of low risk gestational trophoblastic neoplasia –UC1005 Potential trial arms 8 day 50mg I.M. MTX with folinic acid rescue 5 day 125mg/m 2 I.V. MTX Biweekly dactinomycin 1.25mg/m 2 I.V All arms QOL assessment Would a two arm trial 8 day MTX vs Act-D be better?

17. Schema Low Risk GTD WHO Score* 0-6 * WHO 2002 scoring Randomize Pulse Act-D 1.25 mg/m2 every 2 weeks IV Multiday Methotrexate Institutional preference of Either 0.4mg/kg daily x5 IV q 2weeks or CC 8 day regimen with leukovorin rescue Statistical considerations: power to test if experimental (MTX) arm is superior based on GOG 174: based on CR.70 for control arm and.80 for experimental arm power 90%

18. Endometrial Cancer Commitee Agenda Prague October 21, 2010 UPDATE ON ACTIVE STUDIES AGO AGO-GYN 5 Antitumoral activity and safety of AEZS-108 in women with LHRH receptor positive gynecological tumors

19. Endometrial Cancer Commitee Agenda Prague October 21, 2010 UPDATE ON ACTIVE STUDIES: DGOG PORTEC 3 Randomized phase III trail comparing Concurrent Chemoradiation and Adjuvant Chemotherapy with palvic Radiation Alone in High Risk and Advanced Endometrial Carcinoma Participating groups: NCRI, MaNGO, ANZGOG, NCIC-CTG. NSGO interestd.

20. Endometrial Cancer Commitee Agenda Prague October 21, 2010 UPDATE ON ACTIVE STUDIES: GOG GOG-0242 A phase II study to determine the response to Second Currettage as Initial Management of persistent, low risk, non metastatic GTN: 31/66

21. Endometrial Cancer Commitee Agenda Prague October 21, 2010 UPDATE ON ACTIVE STUDIES: GOG GOG-0248 A randomized phase II trial of Temsirolimus or the combination of Hormonal Therapy plus Temsirolimus in women with advanced or recurrent endometrial carcinoma: 60/84 GOG-0249 A phase III trial of pelvic RT vs Vaginal Cuff Brachitherapy followed by Paclitaxel-Carboplatin Chemotherapy in patients with high risk, early stage endometrial cancer: 158/562 Interested group: RTOG

22. Endometrial Cancer Commitee Agenda Prague October 21, 2010 UPDATE ON ACTIVE STUDIES: GOG GOG-0258 A randomized phase III trial of Cisplatin and Tumor Directed RT followed by Carboplatin/Paclitaxel vs Carboplatin/Paclitaxel for optimally debulked advanced endometrial cancer: 120/804. Interested group: RTOG GOG-0261 A randomized phase III trial of Carboplatin-Paclitaxel vs Ifosfamide-Paclitaxel in chemotherapy naive patients with newly diagnosed stage I-IV, persistent or recurrent uterine MMT: 83/424. Interested groups: NCRI, GINECO, JGOG, RTOG

23. Endometrial Cancer Commitee Agenda Prague October 21, 2010 UPDATE ON ACTIVE STUDIES: NCIC CTG NCIC CTG IND 192 Ridaforolimus in treating patients with recurrent metastatic and/or locally advanced endometrial cancer: Completed NCIC CTG IND 179 Phase I of Temsirolimus, Paclitaxel and Carboplatin; have an expanded cohort in endometrial cancer that will continue: completed