GCIG updates PORTEC-3 and PORTEC-4a Lisbon, October 2016 Carien - PowerPoint PPT Presentation

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

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

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

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) 554 – 559

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

Molecular analysis PORTEC-1 and 2 cohort (N=834) The 4 TCGA subgroups by surrogate markers Distant metastasis Overall survival Locoregional recurrence 1 .0 1 .0 1 .0 P - value < 0.001 P - va lu e < 0.0 01 P - value < 0.001 0 .5 0 .5 0 .5 0 .0 0 .0 0 .0 0 5 1 0 0 5 1 0 0 5 1 0 T im e (ye a rs) T im e (ye a rs) T im e (ye a rs) N SM P I p53 M S I P O LE Stelloo et al, Clinical Cancer Research 2016

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

L1-CAM Bosse et al 2014 Zeimet et al 2013 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

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

Molecular integrated risk profile PORTEC-1/2 cohort N=834 1 .0 A rea U nder the C urve * * 0 .8 C lin ica l ( * * * M olecular (P A independent) M olecular (P A in de pe * * * M ole cu la r in te grate d ( 0 .6 0 .4 0 .2 0 .0 L o co re g io n a l D ista n t O ve ra ll su rviva l re cu rre n ce re cu rre n ce  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

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 Drenthe Noord Ijsselmeer Holland Flevoland Overijssel Gelderland Utrecht Zuid Holland Noord Brabant Zeeland Limburg

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

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

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