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

R

Pelvic RT (48.6 Gy)

• uniform schedule
• upfront pathology review
• quality of life analysis

PORTEC - 3

Pelvic RT plus 2x cisplatin

• > 4x carboplatin/paclitaxel
• High risk Endometrial Cancer

686

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)

Stelloo et al, Clinical Cancer Research 2016

P O LE N SM P M S I p53 I

The 4 TCGA subgroups by surrogate markers

Locoregional recurrence

5 1 0 0 .0 0 .5 1 .0 T im e (ye a rs) P -value < 0.001 5 1 0 0 .0 0 .5 1 .0 T im e (ye a rs) P -va lu e < 0.0 01 5 1 0 0 .0 0 .5 1 .0 T im e (ye a rs) P -value < 0.001

Distant metastasis Overall survival

Consistent in independent studies

Talhouk et al, Br J Cancer 2015

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

L1-CAM

Zeimet, JNCI 2013; Bosse, EJC 2014; Van der Putten for ENITEC, Br J Cancer 2016

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 et al 2013 Bosse et al 2014

Stelloo et al, Clinical Cancer Research 2016

Molecular integrated risk profile PORTEC-1/2 cohort

Molecular integrated risk profile PORTEC-1/2 cohort

Stelloo et al, Clinical Cancer Research 2016

• Molecular integrated risk profile is a stronger risk stratification model with

improved risk prediction

• Decrease overtreatment and undertreatment

0 .0 0 .2 0 .4 0 .6 0 .8 1 .0 A rea U nder the C urve

* * * * * * * *

L o co re g io n a l re cu rre n ce D ista n t re cu rre n ce O ve ra ll su rviva l

M ole cu la r in te grate d ( M olecular (P A in de pe

C lin ica l ( M olecular (P A independent)

N=834

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

New PORTEC-4a trial design

• Molecular integrated vs standard indications for adjuvant treatment:

Individual treatment recommendation based on molecular pathology analysis 2 1 Standard treatment recommendation based on clinicopathological factors Vaginal brachytherapy Vaginal brachytherapy (~40%) Observation (~55%) External beam radiation therapy (~5%) Follow-up and Quality of Life Randomisation

Favourable Intermediate Unfavourable

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

PORTEC - 3

International Intergroup Trial

Thanks to all ---