Ομιλία - Παρουσίαση: “Βιοδείκτες: Η Κλινική τους Αξία και η Σχέση τους με τον ΕΟΠΥΥ” Νικόλαος Τσούλος, MSc, MBA, Βιοχημικός, Διευθύνων Σύμβουλος GeneKor Medical SA

1. Βιοδείκτες: Η Κλινική τους Αξία
και η Σχέση τους με ον ΕΟΠΥΥ
Νίκος Τσούλος, Βιοχημικός, MBA, MSc, Διευθύνων
Σύμβουλος GeneKor Medical SA

2. Cancer
Cardiovascular
Diseases
Diagnosis
Prediction
Management
Neurological
Diseases
Genekor is a multinational company
founded in 2007 and is divided into three
different departments:
• Department of Research and
Development of Molecular
Assays
• Department of Molecular
Analysis Implementation
• Department of Scientific
Support and Genetic
Counseling

3. Our goal
• To evolve personalized treatment by
developing and offering molecular
services with increased sensitivity
and specificity.
• To implement those services into
everyday clinical practice
• To incorporate the latest technology
• To provide physicians with the tools
that will help them apply precision
medicine
Response to targeted
treatment
Pharmacogenomics
Identification of
inherited diseases
Scientific support and
counseling
Main
Focus

6. Breast Cancer
Hereditarty
Predispositi
on
Early
Diagnosis
Treatment
Decisions
Monitoring

7. Do I have
predisposition
to develop
cancer?
Can I detect my
cancer before it
becomes life
threatening?
Do I need
chemotherapy?
/What therapy
do I need?
Am I
responding
to my
treatment?

8. Do I have
predisposition to
develop cancer?

9. Do I have
predisposition
to develop
cancer?

10. HEREDiGENE
• 43 genes that helps physicians individualize patients’
surgical and pharmaceutical management.
• It detects which family members belong to the high-risk
category and who can benefit from a personalized risk
reduction program.
• International guidelines recognize the value of the use of
multi-gene panels for hereditary cancer as:
 Cost effective
 More efficient
 More informative

11. Can I detect my
cancer before it
becomes life
threatening?

12. Do I need
chemotherapy?/
What therapy do I
need?

13. Chemotherapy causes both short- and
long-term side effects
13
Neurocognitive dysfunction
Cardiac dysfunction
Fatigue
Premature menopause/
infertility
Nausea/vomiting Secondary cancer
(leukemia)
Persisting peripheral
neuropathy
Myalgia
Neutropenia/Thrombocytopenia
Diarrhoea/constipation
Sepsis
Stomatitis
Working life
Chemotherapy can have an impact
on the patient’s work life, including
increased absences from work for
longer durations and resignation for
health reasons.7,8
Quality of life
Chemotherapy is associated
with a negative effect on quality
of life.4
Family life
Chemotherapy can also affect
family life. The patient’s family
is more likely to take time off
work to provide care during
treatment.7
Extended personal/societal burden
Short-term side
effects of chemotherapy1-5
Long-term side
effects of chemotherapy1,2,4,6
Persisting alopecia
1. Partridge et al. J Natl Cancer Inst Monogr. 2001; 2. Tao et al. Breast. 2015; 3. Kim et al. Breast Cancer Res Treat. 2017; 4. Friese et al. Cancer. 2017; 5. Drolet et al. CMAJ. 2005;
6. Breast cancer and labour force re-entry: the Canadian Breast Cancer Network 2010; 7. Groenvold. Dan Med Bull. 2010; 8. Kuderer et al. Cancer. 2006.

14. EXACT SCIENCES
14
Decision-impact studies confirm the potential of reducing over- and undertreatment
with chemotherapy, as suggested by TAILORx1-5
1. Sparano et al. N Engl J Med. 2018.; 2. McSorley et al. J Clin Oncol 38: 2020 (suppl; abstr 540);
3. Curtit et al. Breast 2019.; 4.Thill, EBCC 2020 poster 367
Risk of
overtreatmenta
Risk of
undertreatmentb
TAILORxc,1
(N=9,719)
73% 9%
Irelandc,2
(N=963)
70% 8%
PONDx – Francec,3
(N=882)
61% 13%
REMAR – Germanyc,4
(N=567)
65% 19%
Decision-impact studies
reflecting real-world
clinical practice
Randomised trial
(level 1A evidence)
N0/N1
N0
N0/N1
N0/N1
a Percentage of patients initially recommended CT-HT based on all clinical pathological parameters and de-escalated to HT alone based on RS® result
b Percentage of patients initially recommended HT based on clinical pathological parameters and escalated to CT-HT based on RS® result
c Patients with unknown values were excluded form the analysis
HT= hormone therapy; CT= chemotherapy
N0/N1 TAILORx, Decision-impact studies

15. EXACT SCIENCES
Surveys reporting real-life clinical practice consistently confirm that use of
the Oncotype DX® test reduces chemotherapy recommendations1-2
A survey of Irish Breast medical oncologists provided the assumption the without Oncotype DX test grade 1
patients would not receive adjuvant CT whereas grade 2 and 3 patients would receive CT
(N=963) Multicenter observational study of HR+, N0 early breast
cancer patients tested with the Oncotype DX® test
from 2011 to 2019.
CT-HT
n= 846
CT-HT
n=262
After testing
69%
Before testing
Decision Impact1
Ireland
Decision Impact2
France & Italy (PONDx)
(N=2,466) Oncotype DX® testing in routine clinical
practice in France & Italy for HR+, HER2-, N0/N1 early
breast cancer patients.
CT-HT
n= 1’339
CT-HT
n=615
Before testing
54%
After testing
TAILORx estimation±
1. McSorley et al. J Clin Oncol 38: 2020 (suppl; abstr 540); 2. Barni et al. ESMO 2018. 194P
N0/N
1
Decision-impact studies
± Excludes 5 patients with incomplete information from the analysis. Treatment
recommendations for N0 patients were simulated, but those for N+ patients were as reported
15
CT= chemotherapy; HT= hormone therapy; HR+= hormone receptor-positive;
HER2= human epidermal growth factor receptor 2

16. EXACT SCIENCES

17. EXACT SCIENCES

18. PriMe
Choosing the right treatment: PrIMe is a Multi-gene assay
that provides an insight of the tumor biology and helps
doctors and patients choose a personalized treatment. It
analyzes 500+ unique cancer genes and the MSI, PD-L1 and
TMB immunotherapy biomarkers, giving the doctor a clear
indication of which treatments will benefit the patient and
which not, including immunotherapy.

19. Τεχνολογία αλληλούχισης επόμενης γενιάς-
NGS: 161-500+ gene analysis
Βιοδείκτες που απαιτούνται για την ανάλυση του πλήρους
προφίλ του όγκου
Γενωμικό προφίλ
+
Φορτίο μεταλλαγών
+
Μικροδορυφορική αστάθεια
+
PD-L1
Βιοδείκτες
ανοσοθεραπείας
Βιοδείκτες για
στοχευμένη
θεραπεία
Comprehensive
genomic profile
Tumor Mutation
Burden
MSI
PARPi
biomarkers
93-99 success
rate

20. Gene/protein Anticancer agent Indications Biomarker Testing
Methods
ALK Crizotinib, ceritinib, alectinib, lorlatinib,
brigatinib
NSCLC ALK translocation FISH, IHC, NGS
BCR/ABL Imatinib, dasatinib, nilotinib, bosutinib,
ponatinib
Chronic myeloid leukemia BCR/ABL1 fusion IHC FISH, NGS,
PCR
BRAF Dabrafenib+trametinib,
vemurafenib+cobimetinib,
encorafenib+binimetinib
Melanoma, NSCLC, anaplastic
thyroid cancer, hairy cell leukemia
BRAF V600E/K mutations IHC, PCR, NGS
BRCA 1/2 Olaparib Breast cancer, ovarian cancer,
Prostate cancer
Germline/somatic BRCA 1/2 mutations NGS
C-KIT, PDGFR Imatinib Gastrointestinal stromal tumor c-KIT PDGFRΑ mutations IHC, NGS
PDGFRA Avapritinib Gastrointestinal stromal tumor PDGFRA D842V mutation NGS
EGFR Gefitinib, erlotinib, afatinib, dacomitinib NSCLC EGFR exon 19 del. exon 21 L858R mut. NGS, PCR
Osimertinib EGFR T790M mutation
KRAS G12C Sotorasib NSCLC KRAS G12C mutation NGS, PCR
FGFR2 Pemigatinib Cholangiocarcinoma FGFR2 fusions NGS, FISH
FGFR2/3 Erdafitinib Bladder cancer FGFR3 mutations, FGFR2/3 fusions NGS, FISH
HRR genes Olaparib Prostate cancer HRR gene mutations NGS
HRD Olaparib, niraparib Ovarian HRD score NGS
MET capmatinib (Tabrecta) NSCLC MET exon 14 alterations FISH, DNA/NGS
MSI-H or dMMR Pembrolizumab MSI-H or dMMR solid tumors MSI high, MMR IHC, NGS, PCR,
NGS
Nivolumab and ipilimumab Colorectal cancer
NTRK Larotrectinib, entrectinib Solid tumors with NTRK fusions NTRK protein expression, NTRK fusion NGS, IHC, FISH
PI3KCA Alpelisib Breast cancer PI3KCA mutation NGS
RAS (negative predictor) Cetuximab, panitumumab Colorectal cancer KRAS/NRAS wildtype NGS
ROS1 Crizotinib, entrectinib NSCLC ROS translocation FISH, NGS
TMB Pembrolizumab Solid Tumors with TMB>10 TMB NGS
Approved Targeted Therapies

21. Am I responding
to my treatment?