What is New in Oncology. Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals

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1 What is New in Oncology Michael J Messino, MD Cancer Care of WNC An affiliate of Mission hospitals

2 Personalized Medicine Personalized Genomics Genomic Medicine Precision Medicine

3 Definition Application of patient specific profiles, incorporating genetic and genomic data as well as clinical and environmental factors to assess individual risks and tailor prevention and disease management.

4 Benefits of Personalized Medicine Improve medical decision making Delivery of appropriate therapy Optimizing disease prevention strategies Reduce incidence of treatment isolated complications Reduce health care cost

5 Argument Against the Benefits Wide scale profiling remains unrealistic High cost of testing Lack of reliable predictive biomarkers for most conditions Lack of knowledge among clinicians for genetics, risk prediction, genetic counseling

6 Personalized Health Care Initiative 2007 Department of Health and Human Service launched the Personalized Health Care Initiative (PHCI) Goal Gene based medical care combined with health information technology

7 Benefits of PHCI Customized treatment based on biology and response Decrease exposure to drugs less toxicity Decrease cost more appropriate prescriptions Targeted prevention strategies Improved satisfaction

8 Biomarkers Biomarkers are available in several specialities Most notable in hematology oncology Early examples L-aspariginase in ALL High dose methotrexate with leucovorin rescue

9 THE STAR TREK MEDICAL TRICORDER 9

10 Chronic Myelogenous Leukemia

11 History of CML Treatment

12 History of CML Treatment Palliative therapy Curative therapy Arsenic Spleenirradiation Busulfan Hydroxyurea Stem Cell transplantation Combination chemotherapy Interferon alpha Imatinib Dasatinib, nilotinib

13 Bone Marrow Transplant (BMT) for CML

14 Development of Imatinib

15 Survival Benefit with Imatinib

16 Breast Cancer Targets for the treatment of breast cancer have included: Estrogen receptors (ER +/-) Progesterone receptors (PR +/-) Her 2 neu oncogene (Her 2 neu +/-)

17 History of Hormone Targeted Therapy for Breast Cancer Surgical Management (1872) (1889)

18 Response to Endocrine Therapy According to ER and PgR Status Response to Tamoxifen ER+, PgR+ 87/ ER+, PgR- 33/ ER-, PgR+ 6/13 46 ER-, PgR- 12/ The assay for PgR can provide valuable additional information that helps predict for response to endocrine therapy Osborne CK et al. Cancer 1980;46:

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20 Action of Hormone Targeted Therapy

21 BREAST CANCER HER-2/neu overexpression HER-2/neu gene is overexpressed in 25% to 30% of breast cancer patients There is a significant decrease in 5-year survival for breast cancer patients who overexpress HER-2/neu This decrease in 5-year survival is significant for both node-positive and nodenegative patients who overexpress HER-2/neu In vitro studies show that HER-2/neu overexpression increased the following cell activities in malignant breast epithelial cells: DNA synthesis Cell growth Anchorage-dependent growth Tumorigencity Metastatic potential Slamon DJ. Chemotherapy Foundation Symposium. 1999;46. Abstract 39. Goldenberg MM. Clinical Therapeutics. 1999;21(2):

22 HER-2 Inhibition

23 The Oncotype DX Report Provides Valuable Information Along a Continuum of ER+ Breast Cancer The Oncotype DX report provides valuable information on: Node-negative prognosis Node-negative predicted chemotherapy benefit Quantitative data on ER/PR/HER2 Node-positive report contains an additional page with prognosis and predicted chemo benefit information specific to nodepositive patients 23

24 DCIS Sample Report: Local Recurrence

25 Non Hodgkins Lymphoma Target CD 20 receptor Rituximab (Rituxan) Zevalin (ibritumomab tiuxetan)

26 Rituxan and Survival Benefit for NHL

27 Radiation and Targeted Therapy (Radiolabeled Targeted Therapy)

28 Hodgkin s Lymphoma

29 Colon Cancer and KRAS

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33 Non Small Cell Lung Cancer Primarily adenocarcinoma Targets: Epidermal growth factor receptor (EGFR) Erlotinib (Tarceva) Anaplastic lymphoma kinase gene (ALK) Crizotinib (Xalkori)

34 Lung Cancer

35 Gastrointestinal Stromal Tumor (GIST) Primary Target C-Kit and PDGFA 80% of patients with GIST have Kit mutation. Kit with exon 11 mutation more responsive to imatinib Agents: Imatinib (Gleevec) Nilotinib (Tasigna) Dasatinib (Sprycel)

36 Gastrointestinal Stromal Tumor (GIST)

37 Renal Cell Targets (multiple) VEGF* Tyrosine kinase inhibitors (TKI) Sunitinib (Sutent), sorafenib (Nexavar), pazopanib (Votrient) Can effect multiple targets (PDGF M-tor kinase inhibitor (mammalian target of rapamycin) Everolimus (Affinitor), temsirolimus (Torisel) *Vascular endothelial growth factor receptor

38 Renal Cell

39 Prostate Cancer

40 Gene Profiling ALL/AML

41 Multiple Targets Identified

42 Summary The goal of cancer treatment historically has been to achieve remission without focus on complications Improvement in medical oncology treatment has allowed for delineation of toxicity and awareness of spectrum of side effects to assure quality of life More specific treatment have improved outcomes and reduced adverse effects Advancements in the biochemistry and pharmacology have improved drug development to specific targets shortening time to use in the clinic 42

43 Conclusion A new ERA in treatment of Cancer has begun Personalized approach to all cancers clearly is not far from reality Genomics and pharmacogenomics is revolutionizing the treatment of cancer and many illness that were most difficult to treat because of lack of understanding Oncology has always been an exciting field because CURE was a word that most other specialties could not use but has always applied to Some patients The word Cure may hopefully be attainable for Most Patients 43

44 H I S T O R y Choosing the Right Hammer Modern Medicine The Future

45 THE STAR TREK MEDICAL TRICORDER 45

46 QUESTIONS?

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