GCIG updates – PORTEC-3 and PORTEC-4a

Lisbon, October 2016

Carien CreutzbergLeiden 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

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The 4 TCGA subgroups by surrogate markers

Locoregional recurrence

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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

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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 > 60Stage IB, grade 1-2 and LVSI+Stage IB, grade 3 without LVSIStage II (microscopic), grade 1

Randomisation

Utrecht

Ijsselmeer

Groningen

DrentheNoord

Holland

Gelderland

Limburg

Flevoland

Zuid Holland

Noord Brabant

Zeeland

Overijssel

Friesland

Waddenzee

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 - 3International Intergroup Trial

Thanks to all ---