Document

Report
Precision Oncology
Istvan Petak MD, PhD
Semmelweis University, Biochemistry Research Group
KPS DIAGNOSTICS KFT
ONCOMPASS MEDICINE ZRT
12,7 MILLION
7,6 MILLION
1:4
GLOBOCAN 2008, WHO
ONCOLOGY IN THE POST-GENOMIC ERA
2003
2013
2014<
6
7
8
9
10 11
12 13
CLINICAL PARAMETERS
1 2 3
4
5
6
7
8
9
10 ….
MOLECULAR TARGETS
1
2 3 4
5
30,000 genes
547 genes
2,1 million
variations
200<
Targeted
Drugs
14
15 …50
LUNG CANCER TREATED WITH
TARGETED THERAPY FOR 1 MONTH
ONLY 5-10% OF LUNG CANCER
PATIENTS BENEFIT FROM THE SAME
TARGETED DRUG
NOT EFFECTIVE, COSTLY TREATMENT
DRUGGABLE DRIVER GENES IN LUNG (NSCLC) CANCER
afatinib 4% (M+)
22% (2X )
20% PLANO (2X )
3% ADENO TKI258 crizotinib
FGFR
gefitinib
erlotinib
5-15% (M+)
5-40% (2X )
4-7% (break)
HER-2
ALK/EML4
EGFR
C-MET
ROS1
3% (M+)
12% (2X ) MET-MAB
crizotinib
2% (M+)
AMP
HEREG
TGFa
KIT
PDGFR
5-20 (M+)
KRAS
NRAS
5% (M+)
HRAS
BRAF
GSK'436
1% (M+)
GSK1120212
5% (M+)
BEZ235
PIK3CA
vemurafenib
MEK
AKT/PKB
PTEN
1% (M+)
MTOR
everolimus
imatinib
sunitinib
„DRIVER” GENES ARE THE BEST TARGETS
RR= 50-100%, PFS= 0,5-1 year /years
BCR/ABL
KIT M+
EGFR M+
EML4/ALK
ROS1+
IMATINIB
NILOTINIB
DASATINIB
BOSUTINIB
IMATINIB
SUNITINIB
GEFITINIB
ERLOTINIB
AFATINIB
CRIZOTINIB
CRIZOTINIB
GIST
MELANOMA
NSCLC
NSCLC
NEUROBLASTOMA
SCLC
OVARIAN,
GASTRIC,
BREAST
CML
ALL
NSCLC
BRAF M+
VEMURAFENIB
MELANOMA
NSCLC
PML
PRECISION ONCOLOGY
TEST
50< GENES
SELECT
TREAT
200<
TARGETED
COMPOUNDS
PERSONALIZED
TREATMENT
STRATEGY
AT PARTNER
ONCOLOGISTS
KPS DIAGNOSTICS
50-60-409
Genes
ONCOMPASSTM
MEDICINE (OCM)
MOLECULAR PROFILING IS ADVANCING
Dana-Farber Cancer Center/Harvard University OncoPanel 305 genes
Sloan Kettering Cancer Center 400+ genes
MDAnderson Cancer Center 400+ genes
Columbia University 500 genes
Washington University UW-OncoPlex™ 194 genes
Foundation Medicine Foundation One /Heme 400 genes
MolecularHealth (Germany) 500 genes
OncoDNA (Belgium) 65-409 genes
MULTIPLEX/NEXT-GENERATION
SEQUENCING IN NCCN GUIDELINES
THE RIGHT PATIENT FOR THE DRUG (OR)
THE RIGHT DRUG FOR THE PATIENT
Registered drug 1
Registered drug 1
DRUG
(registered, in trial)
(HER-2, EGFR, KRAS…)
Companion Diagnostics
PATIENT
Trial drug 2
Companion Therapeutics
261 DRUGS
DRUGS IN CLINICAL USE: (32) AXITINIB, BEVACIZUMAB, BORTEZOMIB, BOSUTINIB,
CABOZANTINIB, CETUXIMAB, CRIZOTINIB, DABRAFENIB, DASATINIB, ERLOTINIB,
EVEROLIMUS,
GEFITINIB,
IMATINIB,
LAPATINIB,
METFORMIN,
NILOTINIB,
PANITUMUMAB, PAZOPANIB, PERTUZUMAB, PONATINIB, REGORAFENIB, RUXOLITINIB,
SORAFENIB, SUNITINIB, TEMSIROLIMUS, TRAMETINIB, TRASTUZUMAB, TDM-1,
VANDETANIB, VEMURAFENIB, VISMODEGIB, ZIV-AFLIBERCEPT
DRUGS IN CLINICAL TRIALS: (173) AKN-028, AMG 208, AMG 319, AMG 337, AP26113,
ARQ 092, ARQ 736 , ASP-3026, AT13148, AT9283, AUY922, AV-412 , AXL1717, AZD0424,
AZD1480 , AZD2014, AZD4547, AZD5363, AZD8330 , BAY1000394, BEZ235 , BGJ398,
BGT226, BKM120, BMN 673, BMS-777607, BMS-911543, BRIVANIB, BYL719, CC-223,
CEDIRANIB, CH5424802, CO-1686, CRENOLANIB, DALOTUZUMAB, DACOMITINIB,
DEMCIZUMAB, DKN-01, DOVITINIB, DS-7423, E-3810, E6201, EMD 1204831, EMD
1214063, ERISMODEGIB, FORETINIB, GANITUMAB, GDC-0068, GDC-0623 , GDC-0941,
GDC-0973, GDC-0980, GOLVATINIB, GSK1059615, GSK1838705A, GSK2110183 ,
GSK2126458, GSK2141795, GSK2636771, GSK343, GSK-461364, HM61713, IMC-CS4,
INIPARIB, JNJ-42756493, KU 55933, LDK-378, LENVATINIB, LESTAURTINIB, LGX818 ,
LINSITINIB, LJM716, LY2109761, LY2157299, LY2606368 , LY2780301, LY287445,
MASITINIB, MEDI-573, MEK-162, MGAH22, MGCD265, MIDOSTAURIN, MK-0752, MK2206, MK-8242, MLN1117, MM-302, MOMELOTINIB, NECITUMUMAB, NERATINIB,
NINTEDANIB, NS-398, OLAPARIB, OLARATUMAB, ONARTUZUMAB, OSI-027, P7170,
PACRITINIB, PD0325901, PD0332991, PD173074, PF-03084014, PF-04217903, PF04691502 , PF-04856884, PF-477736, PIMASERTIB, PKI-179, PRI-724, PX-866, R04929097,
RABUSERTIB, RAF265, RAMUCIRUMAB, REBASTINIB, REFAMETINIB, RIDAFOROLIMUS,
RILOTUMUMAB, RO4987655, RO5212054, RUCAPARIB, SAR125844, SARACATINIB,
SARIDEGIB, SCH 900776, SELUMETINIB, SEMAGACESTAT, SGX523, SR13668, SU-1127,
TAE684, TAK-733, TAK-960, TG101348, TILMACOXIB, TIVANTINIB, TIVOZANIB,
TREBANANIB, TRICIRIBINE, VELIPARIB, VOLASERTIB, VX-509, WX-554, WHI-P154, X-396, X82, XL019, XL147, XL281, XL765, ZM39923, ZSTK474
58 GENES
58 genes for NGS: ABL1, AKT1, ALK, APC,
ATM, BRAF, CDH1, CDKN2A, CSF1R,
CTNNB1, EGFR, ERBB2, ERBB4, FBXW7,
FGFR1, FGFR2, FGFR3, FLT3, GNAS,
HNF1A, HRAS, IDH1, JAK2, JAK3, KDR, KIT,
KRAS, MET, MLH1, MPL, NOTCH1, NPM1,
NRAS, PDGFRA, PIK3CA, PTEN, PTPN11,
RB1, RET, SMAD4, SMARCB1, SMO, SRC,
STK11, TP53, VHL
FISH: EGFR, HER-2, FGFR, ALK, MET,
ROS1. PIK3CA
Peták I, Schwab R, Orfi L, Kopper L, Kéri G. Integrating molecular diagnostics
into anticancer drug discovery. Nat Rev Drug Discov. 2010 Jul;9(7):523-35.
OncompassTM: IT support for
precision medicine
MOLECULAR TUMOR BOARD
Other Physicians with Experience in Molecular Oncology
Oncologists with experience with the same therapy or molecular profile
Principal investigators of clinical trials
OCM Information Technologies
Special Decision Support Software
Databases, Experts in cancer biology,
genetics, bioinformatics
Molecular Diagnostics
Treating physicians
OUR PARTNERS
Amongst many...
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Köln TP (free of charge-several
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Barcelona TP (1000E, 700E,
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Hungary TP (free)
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Miláno-coming up
LUNG CANCER PATIENT IN CLINICAL
TRIAL IN SPAIN
MALAGA
INFORMATION
WHO BENEFITS FROM
PRECISION ONCOLOGY?
PATIENTS
longer, better
life
DOCTORS
more success
INSURANCE
more health benefit
for less cost
THANK YOU FOR YOUR KIND ATTENTION!
[email protected]

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