Endometrial Cancer Committee

Transcription

1 Endometrial Cancer Committee REPORT to G.A. Chicago, May 2018 Chair: S. Greggi/Co-Chair: C. Creutzberg

2 EN Committee Chicago, 31 May 2018 Closed Trials Status Update

3 CLOSED TRIALS EC Newly Diagnosed or Recurrent Uterine Carcinosarcoma Trial Name Trial Description # pts enrolled/total Lead Group/Contact person JGOG-2047 Prospective Randomized Phase II-III Comparing Dose-dense Paclitaxel and Carboplatin (TC) vs Conventional Triweekly TC Therapy Start date: Jan 2, 2017 JGOG Premature trial closure: Low accrual; lack of financial support

4 EN Committee Chicago, 31 May 2018 Ongoing Trials Status Update

5 ONGOING TRIALS EC Conservative Treatment of Selected Early Stage Disease Trial Name Trial Description # pts enrolled/total Lead Group/Contact person E.C.Co. Observational Patient Archive Based on an IRB-approved local protocol that allows conservative treatment to be performed (or statement that such treatment is considered as a standard) First report in preparation 70 from 6 centres (MITO, MANGO) 5 centres from: AGO-Au, ANZGOG SHANGAI DGOG AGO registered but not yet active MITO / S. Greggi

6 ONGOING TRIALS EC Adjuvant Treatment in Int./High-risk Early Stage Disease Trial Name Trial Description # pts enrolled/total PORTEC-4 Prospective Randomized Phase III 130/500 Lead Group/Contact person DGOG / C. Creutzberg Molecular profile-based vs standard recommendations for adjuvant RT Pilot Phase: Logistics of molecular analysis (<2wks); Patient acceptance. (N=50) completed 35% pt acceptance 84% path. review within 2wks NCRI ANZGOG, CTI (former ICORG), GINECO, planning to participate, awaiting grant application, validation of pathology labs

7 ONGOING TRIALS EC Treatment of Advanced/Rec. Disease Trial Name Trial Description # pts enrolled/total Lead Group/Contact person ENGOT-EN1 FANDANGO Prospective Randomized Phase II CT (carbo-tax x6) + Nintedanib Vs CT + placebo 100/ activated sites NOGGO BGOG GINECO NSGO / M. R. Mirza

8 ONGOING TRIALS EC LND-guided Adjuvant Treatment in Int./High-risk Disease Trial Name Trial Description # pts enrolled/total Lead Group/Contact person ENGOT-EN2 DGCG Prospective Randomized Phase II LN ve Int./High-risk EC 199/240 NSGO / M. R. Mirza CT /carbo-tax x6) + BRT vs Observation + BRT 5-y Survival, AE, QoL MITO MANGO GEICO BGOG NOGGO CEEGOG C-GOG (MDACC)

9 ONGOING TRIALS EC Treatment of Advanced/Rec. Disease Trial Name Trial Description # pts enrolled/total ENGOT-EN3 PALEO Prospective Randomized Phase II ER +ve Advanced/Rec. EC Letrozole + Palbociclib vs Letrozole + Placebo 42/78 GEICO NOGGO MITO still pending (AIFA and EC approval) Lead Group/Contact person NSGO / M. R. Mirza

10 ONGOING TRIALS EC Maintenance Therapy in Advanced/Rec. Disease Trial Name Trial Description # pts enrolled/total Lead Group/Contact person ENGOT-EN5 S-I-ENDO Prospective Randomized Phase III Advanced/Rec. EC Required: 161 Enrolled: 4 BGOG / I. Vergote Selinexor first-in-class inhibitor of XPO1 (exportin1, the only nuclear exporter of major TSPs) induces nuclear retention, accumulation and activation of TSPs, leading to tumor apoptosis Selinexor vs Placebo (until PD) Primary EP: PFS FPI: Jan 2018 LPI: Q Activated sites BGOG: 4/11 Pending sites GEICO: 0/15 NOGGO: 0/8 MITO: 0/8 CEEGOG: 0/5

11 ONGOING TRIALS EC LND-Guided Adjuvant Treatment in HR Early Stage Disease Trial Name Trial Description # pts enrolled/total Lead Group/ Contact person STATEC Prospective Randomized Phase III 12/2000 NCRI / T. Mould Sel. Targeting Adjuvant Therapy End. Ca. Pe+Ao LND vs Standard Surgery LN ve: BRT NCRI: 7 sites open, 25 in set-up ANZGOG: 3 sites open, 10 in set-up DGOG: 14 sites in set-up LN +ve or unknown: CT + RT 5-y Survival, AE, QoL

12 ONGOING TRIALS EC LND (syst.) impact on survival in HR Early Stage Disease Trial Name Trial Description # pts enrolled/total Lead Group/Contact person ECLAT Prospective Randomized Phase III Required: 640 AGO / G. Hemons; P. Harter Stage IB-II Stage IA G3 (type I) Stage IA (type II) No bulky N Aortic & Pelvic LND vs Standard Enrolled: 2 40 German sites qualified Primary EP: OS (DSS)

13 EN Committee Chicago, 31 May 2018 Activating Trials

14 ONGOING TRIALS EC Treatment of Advanced/Rec. Disease Trial Name Trial Description # pts enrolled/total Lead Group/Contact person ENGOT-EN6 (TSR042) Stratification: MSI-H vs. MSS Prior RT Rec. disease Prosp. Randomized Phase III - Inoperable Stage IV - Stage III-IV with macro RT - Stage IV - NACT - First relapse after primary stage I-II (+/- adjuvant CT) Paclitax + Carboplatin x6 + TSR042 concom. & maint. vs Paclitax + Carboplatin x6 Primary End-point: PFS 520 Not yet recruiting FPI Q NSGO / M. R. Mirza

15 ONGOING TRIALS EC Treatment of Advanced/Rec. Disease Trial Name Trial Description # pts enrolled/total Lead Group/Contact person ENGOT-EN7 At-TE-nd Stratified by Prior RT Rec. disease MSI Prospective Randomized Double-blind Parallel Arms Advanced/Rec. EC CT (carbo-tax x6) + Atezolizumab followed by Atezo maintenance vs CT + Placebo followed by Placebo maintenance Primary EP: OS & PFS Required: 550 Not yet recruiting FPI planned July 2018 GEICO AGO A-AGO PolskaGOG NCRI SAKK (JGOG) (ANZGOG) MaNGO / N. Colombo

16 ACTIVATING TRIALS EC Cytoreductive Surgery in Advanced Disease Trial Name Trial Description # pts enrolled/total Lead Group/Contact person ADV-EN Multicenter Retrospective Study 20/500 MITO / S. Greggi Advanced EC (type I-II) FIGO Stage: IIIA bulky*; IIIB; IIIC bulky*; IVA; IVB intra-abd. treated *preop. Imaging/intraop. Treatment strategy adopted Predictors of survival Predictors of complete surg. cytoreduction Biomolecular TGCA grouping analysis (FPI Q2 2018) Sites active: 1 Sites open: 7 AGO NOGGO NCRI SAKK SHANGAI Subsequent prospective phase to validate

17 EN Committee Chicago, 31 May 2018 New Proposals

18 David Gaffney Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) in Early Endometrial Cancer Compared to Standard of Care (SAVE) 2 fractions of VCB vs standard of care may allow: > compliance Non-inferior pt satisfaction (PROs) > pts to receive VCB < intensive on RT resources > cost effective Maintain a high rate of local control Primary Objective: pt rep. outcomes (PROs) (Global H. Score QLQ30) Secondary Objectives: cost effectiveness; CTCAE v4 toxicities; pattern of recurrence; PROs for vaginal, bladder, bowel symptoms (EORTC EN24) R 2 Fractions 11 Gy at the surface (7.3 Gy at ½ cm for a 3 cm cylinder) Standard of care brachytherapy 1. 7 ½ cm x ½ cm x surface x 5 Planned Sample Size: 108 (90% power)

19 EN Committee Chicago, 31 May 2018 CHALLENGING DEBATE Use of Molecular Factors in the Clinic. Is it time to change? Background & audience vote.. S.Greggi Molecular stratification: feasibility data from PORTEC4...C.Creutzberg Could biomolecular profiling on diagnostic biopsy help in tailoring surgery?... J.Sehouli

20 COLO-RECTAL CA LUNG CA BREAST CA ENDOMETRIAL CA

21 Is any form of biomol. stratification performed at your Institution? 25% If yes, is this already entered into the routine primary pathological assessment? If yes, is this performed on diagnostic specimens? If yes, is this performed on explorable recurrent disease? 3% Is it time for the implementation of a routine biomol. profiling? What s the major problem(s) for the implementation of a routine biomol. profiling? - technical resources & logistics More than resources/costs, - costs lack of well designed clinical trials supporting the opportunity of a - both routine implementation - other 5% 85% 20%

22 PORTEC-4a profile decision tree Pilot Phase (N=50): Logistics of mol. analysis (<2wks) Patient acceptance. 35% pt acceptance 84% path. review within 2wks Stelloo et al, Clinical Cancer Research 2016

23 GCIG Endometrial Committee Debate Chicago, 31 May 2018 Could biomolecular profiling on diagnostic biopsy already help in tailoring surgery? Jalid Sehouli

24 Prospective data are needed Abrasio/ Uterus (Sentinal) lymph node distant metastasis Liquid biopsy What s about heterogeneity? SehouliGCIG2018

25 Tailored Surgery in Endometrial cancer potential cohorts GROUP A No surgery GROUP B Total hysterectomy only GROUP C Total hysterectomy + systematic lymph node dissection GROUP D Tumor debuking/ cytoreduction SehouliGCIG2018

26 MyLord, ask me a your «impossible» wish! I d have one, are you sure? OK,..Genius! Find now a HONEST POLITICIAN! Nothing is impossible for me!! GOSH!!! This is really over my powers! Are we ready? «It s kind of fun to do the impossible!» Walt Disney