Individualized Cancer Therapy: Chemotherapy Resistance Testing before Therapy 1 st st International Oncological Conference Wrocław, October 6 th, 2012 Dr. Frank Kischkel
Individualized Cancer Therapy: Drug Treatment Testing before Therapy 1 st st International Oncological Conference Wrocław, October 6 th, 2012 Dr. Frank Kischkel
Individualized Cancer Therapy: Drug Treatment Testing before Therapy Chemotherapy- Resistance-Test
Individualized Cancer Therapy Introduction Therapy Healing or Relief Diagnostics Cancer
Individualized Cancer Therapy Introduction CTR-Test ONCOMPASS TM Therapy Healing or Relief Diagnostics Cancer
Individualized Cancer Therapy Introduction Treatment Options Therapy Healing or Relief Diagnostics Cancer
Treatment Options for Cancer Introduction Irradiation Surgery Medication Type Action Target Chemotherapeutic drugs Hormones Inhibitors of signal transduction Cell division Cell division Inside (Tumor) cells TC TC TZ, VZ Tumor Antibodies (monoclonal) Outside (Tumor) cells TC, VC, IC Immunotherapy Gene therapy Zytokines Immunomodulation IC TC Tumor cells; VC Vascular cells; IC Cells of the immune system
Treatment Options for Cancer Introduction Irradiation Surgery Medication Type Action Target Chemotherapeutic drugs Hormones Inhibitors of signal transduction Cell division Cell division Inside (Tumor) cells TC TC TZ, VZ Tumor Antibodies (monoclonal) Outside (Tumor) cells TC, VC, IC Immunotherapy Gene therapy Zytokines Immunomodulation IC TC Tumor cells; VC Vascular cells; IC Cells of the immune system
CTR-Test Test can evaluate all drugs that act against cancer cells directly Medication Type Action Target Chemotherapeutic drugs Hormones Inhibitors of signal transduction Cell division Cell division Inside (Tumor) cells Introduction TC TC TZ, VZ Antibodies (monoclonal) Zytokines Outside (Tumor) cells Immunomodulation TC, VC, IC IC TC Tumor cells; VC Vascular cells; IC Cells of the immune system
ONCOMPASS Can Evaluate All Targeted Drugs Introduction Medication Type Action Target Chemotherapeutic drugs Hormones Inhibitors of signal transduction Cell division Cell division Inside (Tumor) cells TC TC TZ, VZ Antibodies (monoclonal) Zytokines Outside (Tumor) cells Immunomodulation TC, VC, IC IC TC Tumor cells; VC Vascular cells; IC Cells of the immune system
Chemotherapy- Resistance-Test CTR-Test
The Logistic Chain CTR-Test Tumor removal Transport Cancer patient Optimized Chemotherapy Duration: 7-9 days Chemotherapy- Resistance-Test Test result Oncologist
The Procedure CTR-Test Tumor Plating of Addition of Addition of preparation tumor cell chemotherapeutic 3H-labeled suspension drugs thymidine Different cell growth Isolation of genomic DNA Reading of incorporated 3H-activtiy Computing test result
The Test Report CTR-Test Standard distribution of a drug effect
CTR-Test The Test Report Drug A Slight Drug Resistance (SR) Medium Drug Resistance (MR) Extreme Drug Resistance (ER) Drug B Drug C Drug D Drug E Drug F Drug G -1 µ 1 2 Relative in vitro cell growth
Correlation of CTR-Test Test Result and Clinical Response CTR-Test N = 450, Overall response rate = 29% Slight Resistence Test result Relative in vitro cell gr rowth ER Medium Resistance Extreme Resistence Non-Responder Clinical Response Responder Kern DH, Weisenthal LM (1990) J Natl Cancer Inst. 82(7):582-8
Correlation of CTR -Test Result and Overall Survival CTR-Test Survival in % SR for platinum drugs (n-62) ER for platinum drugs (n-17) Time in months Holloway et al. (2002) Gynecologic Oncology 87(1):8-16
Extended Survival by Treatment According to Test Result CTR-Test Ovarian cancer, platinum-sensitive group Treatment according to test results (n = 31) Survival in % Treatment according to physician s choice (n = 31) Time in months Loizzi et al. (2003) Am J Obstet Gynecol 189(5): 1301-1307
CTR-Test Best Drug Combination Correlates with Single Active Drugs Kaplan-Meier progression free survival curves for patients with ER scores of 4 vs. 2-3 vs. 0-1. ER Score = 4 ER Score = 0-1 ER Score = 2-3 Mehta RS et al. (2001) Breast Cancer Research and Treatmant 66(3): 225-237.
KPS DIAGNOSTICS GmbH
MOLECULAR ONCOLOGY REVOLUTION
FIRST PROSPECTIVE TREATMENT OF A EGFR MUTANT NSCLC PATIENT 2003 2004 2009 G FISH+SEQ Modern treatment of lung cancer: case 1. Amplification and mutation of the epidermal growth factor receptor in metastatic lung cancer with remission from gefitinib. Schwab R, Pinter F, Moldavy J, Papay J, Strausz J, Kopper L, Keri G, Pap A, Petak I, Oreskovich K, Mangel L. J Clin Oncol. 2005 Oct 20;23(30):7736-8.
RESPONSE TO EGFR INIBITORS IS INDEPENDENT FROM EGFR IHC Tissue- Clinical Gen. Smoker Sample Age EGFR TK Case TKI mutation Response Rtr 1 ADC 58 Fem. Never del747-753inss gefitinib CR Analyis R e t r o s p P r o s p e k t í v Rtr 2 ADC 68 Fem. Never del746-750 erlotinib CR Rtr 3 adsq. c. 62 Fem. Smoker L858R erlotinib CR Rtr 4 ADC 66 Fem. Never del746-750 erlotinib PR Rtr 5 ADC 50 Male Never del746-751insa erlotinib PR Rtr 6 ADC 65 Fem. Never L858R erlotinib PR Rtr 7 ADC 72 Fem. Never del746-750 erlotinib PR Rtr 8 anap. c. 54 Male Smoker del746-750* erlotinib SD Pr 1 ADC 61 Fem. Never del747-750insp gefitinib CR Pr 2 ADC 45 Fem. Never del746-752insv gefitinib CR Pr 3 ADC 50 Male Smoker del747-753inss erlotinib CR Pr 4 ADC 55 Fem. Never del746-750 erlotinib CR Pr 5 ADC 59 Fem. Never L858R gefitinib CR Pr 6 ADC 67 Fem. Never del746-750 erlotinib PR Pr 7 ADC 53 Fem. Never L858R erlotinib PR Pr 8 ADC 67 Male Never L858R erlotinib PR Pr 9 ADC 64 Fem. Never L858R erlotinib PR primer: Pr 10 ADC 55 Male Never L858R erlotinib PR, meta:
Molecular SAMPLE Diagnostic TYPES FOR MOLECULAR Platform PATHOLOGY BRUSH NEEDLE 26% LUNG 52% CT CYTOLOGY SMEAR 22% EXCISOR SURGICAL FFPE BLOCK COLON 10% ENDSOCOPY 90% SURGICAL LIVER METASTASIS 10% BIOPSY SURGICAL
SUCCESSFUL MULTIPLEX MOLECULAR PDX IN EXTREMELLY SMALL SAMPLES WITH ZEISS-PALM LASER CAPTURE MICROSCOPY BY TRANSFERING THE CELLS DIRECTLY FROM THE SLIDE TO THE PCR TUBE FOR AMPLIFICATION WITHOUT DNA EXTRACTION 100% LCM (ZEISS-PALM) OPTIMIZED DIRECT PCR MULTIPLEX XS-DX TM
DETECTION OF EGFR MUTATION IN 84 CELLS 28 db 56 db EGFR EXON 21 L858R Response to gefitinib therapy
NEXT GENERATION CLONAL SEQUENCING CAN PROVIDE HIGH THROUGHPUT INFORMATION ON POTENTIAL TARGETS AND ALSO ABOUT THE MOLECULAR HETEROGENICITY UP TO 1 MILLION PARALLEL PYROSEQUENCING UP TO 1000 BP READ LENGTH
3X 100% RESULTS IN RING TRIALS
ONCOMPASS TARGET 18 TARGETS 20 DRUGS ALK: BRAF EGFR: ERBB2/HER-2 ERBB4/HER-4 FLT3 KRAS HRAS NRAS KDR (VEGFR2) KIT PDGFR RET MET ABL SRC PIK3CA PTEN crizotinib vemurafenib erlotinib, gefitinib, cetuximab, panitumumab trastuzumab, lapatinib, pertuzumab, lapatinib sunitinib erlotinib, cetuximab, panitumumab cetuximab, panitumumab cetuximab, panitumumab pazopanib, sunitinib, sorafenib imatinib, sunitinib, dasatinib, nilotinib sunitinib, pasopanib, sorafenib vandetanib, sunitinib crizotinib imatinib, dasatinib, nilotinib dasatinib everolimus,temsirolimus, metformin, cetuximab, anti-eostrogens everolimus, metformin cetuximab, anti-eostrogens
ONCOMPASS DRUG SENSITIVITY DATABASE
ONCOMPASS TARGET-DRUG ASSOCIATION ANALYZER
~100 TARGETS ~400 DRUGS WHICH DRUG? WHICH PATIENTS?
ONCOMPASS TARGETED CLINICAL TRIAL DATABASE CLINICAL TRIALS IN COLON CANCER PIK3CA MUTANT SOLID TUMORS CLINICAL TRIALS IN NSCLC PIK3CA MUTANT COLON CANCER BIOMARKER PIK3CA INHIBITORS ORGAN LINE TYPE OTHER MARKER.. PIK3CA BKM120 COLON 2nd Phase 1,II KRAS WT.. PIK3CA BYL719 SOLID TUMORS 2nd Phase I. PIK3CA M+/AMP.. PIK3CA temsirolimus SOLID TUMORS - Phase I PIK3CA/ PTEN M+................
ONCOMPASS TARGETED CLINICAL TRIAL NAVIGATOR AND PATIENT ASSISTANCE MET PDGFR EGFR HER-2 KIT AKT KRAS HRAS ALK NRAS PIK3CABRAF
Contact Data TherapySelect Dr. Frank Kischkel Carl-Bosch-Str. 4 69115 Heidelberg, Germany Tel.: +49 (0) 6221 8936 152 Fax: +49 (0) 6221 8936 153 info@therapyselect.de www.therapyselect.de