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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... Köln, Germany Köln TP (free of charge-several 1000s E) Essen, Germany Essen FV Barcelona Barcelona TP (1000E, 700E, 400E)Spain Malaga, Spain Malaga TP (free of charge) London, UK London FV (NHS or cash) Leuven, Belgium Switzerland FV (charge) Milano, It Hungary TP (free) Romania Budapest, Hu 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]