GCIG updates PORTEC-3 and PORTEC-4a

Transcription

1 GCIG updates PORTEC-3 and PORTEC-4a Lisbon, October 2016 Carien Creutzberg Leiden University Medical Centre, The Netherlands

2 The PORTEC-3 trial High risk Endometrial Cancer R Pelvic RT (48.6 Gy) 686 Pelvic RT plus 2x cisplatin -> 4x carboplatin/paclitaxel uniform schedule upfront pathology review quality of life analysis PORTEC - 3

3 PORTEC-3 trial toxicity and quality of life De Boer et al, Lancet Oncology 2016

4 PORTEC-3 progress and analysis Radiotherapy QA to be completed this year Ongoing data checks, queries, FU information and QOL ANZGOG: TROG benchmarking study published* Patient preferences study accepted to BJC Analysis of pathology review completed (NL-UK) TransPORTEC consortium for translational research Final analysis of PORTEC-3 expected 2017 depending on timely follow-up information and prompt reporting of events! * Jameson et al, Journal of Medical Imaging and Radiation Oncology 60 (2016)

5 Molecular characteristics of endometrial cancer TGCA, Kandoth et al, Nature 2013

6 lity o f e n c e ility o f e n c e C u m u la tiv e p ro b a b ility o f d is ta n t re c u rre n c e O v e ra ll S u rviv a l Molecular analysis PORTEC-1 and 2 cohort (N=834) The 4 TCGA subgroups by surrogate markers L E Locoregional N S M Precurrence M S I p 5 3 Distant metastasis Overall survival 1.0 P -v a lu e < P -v a lu e < p 5 3 P -v a lu e < M S I P O L E N S M P T im e (y e a rs ) T im e (y e a rs ) T im e (y e a rs ) N S M P P O LME S I N ps 5M 3P M S I p 5 3P O L E N S M P M S I p P -v a lu e < P -v a lu e < P -v a lu e < Stelloo et al, Clinical Cancer Research 2016

7 Consistent in independent studies A clinically applicable molecular-based classification for endometrial cancers 152 -> 143 patients evaluable 17% serous/mixed 39% low risk, 16% intermediate risk, 45% high risk Talhouk et al, Br J Cancer 2015

8 L1-CAM Zeimet et al 2013 Bosse et al 2014 L1-CAM strong negative prognostic factor About 7-10% overall L1CAM+ More often L1CAM+ in grade 3, p53+, NEEC Confirmed in large ENITEC series (n=1200) Zeimet, JNCI 2013; Bosse, EJC 2014; Van der Putten for ENITEC, Br J Cancer 2016

9 Molecular integrated risk profile PORTEC-1/2 cohort Stelloo et al, Clinical Cancer Research 2016

10 A re a U n d e r th e C u rv e A re a U n d e r th e C u rv e A re a U n d e r th e C u rv e Molecular integrated risk profile PORTEC-1/2 cohort N= * * * * * * * * * * * * * * * * * * * * * * C C lin lin ic a icl l (P a l A (Plo loa c ca alo l) l) c a l) M Mo le oc le u cla ur la (P (Pr A (P in ind A de ep inp e ed n nd ed pn e nnt) d e n MM o le ocle u cla lau r r la in inte r tein gg ra ra te te te gd ra d (P (P tea A d lo lo (P c ac l) A a l) lo L o c o re g io n a l D is ta n t O v e ra ll s u rv iv a l L o c o re re c g u io rre n n a c l e D re is c ta u rre n t n c e O v e ra ll s u rv iv a l re c u rre n c e re c u rre n c e L o c o re g io n a l D is ta n t O v e ra ll s u rv iv a l re c u rre n c e re c u rre n c e Molecular integrated risk profile is a stronger risk stratification model with improved risk prediction Decrease overtreatment and undertreatment Stelloo et al, Clinical Cancer Research 2016

11 New PORTEC-4a trial design Molecular integrated vs standard indications for adjuvant treatment: Endometrial carcinoma Surgery and pathology diagnosis FIGO 2009 high intermediate risk Stage IA (with invasion), any age and grade 3 (with or without LVSI) Stage IB, grade 1-2 and age > 60 Stage IB, grade 1-2 and LVSI+ Stage IB, grade 3 without LVSI Stage II (microscopic), grade 1 Randomisation Groningen Waddenzee Friesland Noord Holland Ijsselmeer Drenthe Flevoland Overijssel Zuid Holland Utrecht Gelderland Noord Brabant Zeeland Limburg

12 New PORTEC-4a trial design Molecular integrated vs standard indications for adjuvant treatment: Randomisation Individual treatment recommendation based on molecular pathology analysis 2 1 Standard treatment recommendation based on clinicopathological factors Favourable Intermediate Observation (~55%) Vaginal brachytherapy (~40%) Vaginal brachytherapy Unfavourable External beam radiation therapy (~5%) Follow-up and Quality of Life

13 PORTEC-4a pilot phase started Pilot phase: N = 50 (Netherlands) Endpoints: logistics, patient acceptance Ongoing site activations; first 7 patients randomised Proceed into full trial (international) Endpoints: vaginal recurrence, recurrence-free survival, AE and QOL, health costs Validation of molecular profile procedure in pathology centers NCRI UK and ANZGOG planning to participate Trial specific meeting Friday 28 Oct, 12:30 pm, Augusta I room

14 Thanks to all --- PORTEC - 3 International Intergroup Trial