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11 th Annual Symposium on Prostate Cancer

11 th Annual Symposium on Prostate Cancer. Wednesday, September 23, 2009. Prevention • Screening • Detection • Treatment. Lank Center for Genitourinary Oncology Multidisciplinary and multi-specialty care and treatment center

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11 th Annual Symposium on Prostate Cancer

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  1. 11th Annual Symposium on Prostate Cancer Wednesday, September 23, 2009 Prevention • Screening • Detection • Treatment

  2. Lank Center for Genitourinary Oncology • Multidisciplinary and multi-specialty care and treatment center • Staffed by medical, urologic, and radiation oncologists, plus a comprehensive range of support services • Cutting-edge research facility— a place where discovery is transformed into more effective diagnostics and safer and more effective treatments

  3. Jonathan E Rosenberg, MD Clinical Director, Lank Center for Genitourinary Oncology

  4. Outline • Developing Personalized Medicine • Exciting New Treatments on the Horizon

  5. Current Paradigm Biopsy Prostate cancer Treatment

  6. Better Paradigm? Biopsy Treatment C Prostate cancer Sub-classification Treatment A Treatment B

  7. Risk of prostate cancer death based on Gleason score Gleason 2-6 cancers 1% 15-year PCSM 1 of 3756 patients with organ-confined, Gleason 2-6 cancers has died from prostate cancer Pathological Gleason 8-10: 49% 15-year PCSM Account for 6% of cancers but 45% cancer deaths G8-10 G4+3 G3+4 G3+3

  8. What is Personalized Medicine? • Tailoring treatment to the genetics of an individual and to the genetics of the tumor

  9. Personalized Medicine Approach-Where Are We? • New understandings of inherited (genetic) tendencies • To develop cancer • To respond to treatments • We soon will be able to determine an individual’s tumor genetics • Cost of sequencing all the genes in a tumor now is becoming feasible • Understand how it changes over time through circulating tumor cells

  10. Exciting New Drugs • Androgen pathway (hormones) • Vaccines

  11. AR AR AAA AR AR AR ARE AR AR Target Genes AR gene HSP AR androgen HSP AR mRNA AAA

  12. AR AR AAA AR AR AR ARE AR AR Target Genes AR gene HSP AR androgen HSP AR mRNA AAA

  13. Androgens • Prostate cancer cells rely on testosterone and other male hormones to grow and spread • Mainstay of treatment of advanced prostate cancer is “hormonal therapy” • Elimination of testosterone • Most prostate cancers eventually become resistant to this maneuver • Castration resistant prostate cancer (CRPC) • Better targeting of the androgen pathway may lead to better prostate cancer treatments

  14. Abiraterone • Oral medication targeting testosterone and other androgen production in the body • Abiraterone is a potent inhibitor of testosterone synthesis proteins • High response rate in CRPC • Lowers serum testosterone to extremely low levels (<1ng/dl) • Androstenedione and DHEA lowered effectively in CRPC

  15. Pre-docetaxel Phase I/II (n=54):Maximal PSA Declines after Abiraterone Monotherapy 38/54: PSA↓ ≥50% (70%) 43/54: PSA↓ ≥30% (80%)

  16. Post-docetaxel Phase IIMaximal Change in PSA (n=34) 17/34 (50%) pts ≥50% decline 22/34 (65%) pts ≥30%decline 24/34 (71%) pts had a PSA decline 3 pts did not reach 12-weeks but are included

  17. AR AR AAA AR AR AR ARE AR AR Target Genes AR gene HSP AR androgen HSP AR mRNA AAA

  18. AR AR AAA AR AR AR ARE AR AR Target Genes AR gene HSP AR androgen HSP AR mRNA AAA

  19. MDV3100 Small molecule AR antagonist with a novel mechanism of action that blocks the ability of the AR from getting into the nucleus Active in Casodex-resistant prostate cancer models Oral medication, generally well tolerated

  20. Waterfall Plot of Percent PSA Change from Baseline at 12 Weeks for Chemotherapy-Naïve Patients Treated at 60, 150, and 240 mg/day 7 pt off study <12 weeks N=42 Chemo-naïve >50% Decline: 23/42 (55%)

  21. PSA Declines at 12 Weeks for Post-Chemotherapy Patients 5 pt off study <12 weeks N=31 Post-chemo >50% Decline: 13/31 (42%)

  22. Immune system and prostate cancer • Scientists have known for several years that the immune system can fight cancer • Harnessing that has proved difficult • Several new treatments are showing promise • Not “vaccines” in the typical sense

  23. Sipuleucel-T (Provenge) Day 1 Leukapheresis Day 2-3 sipuleucel-T is manufactured Day 3-4 Patient is infused Apheresis Center Doctor’s Office COMPLETE COURSE OF THERAPY: Weeks 0, 2, 4

  24. Provenge: IMPACT Overall Survival: Primary Endpoint Intent-to-Treat Population Provenge (n = 341) Median Survival: 25.8 Mos. Placebo (n = 171) Median Survival: 21.7 Mos. P = 0.032 (Cox model) HR = 0.775 [95% CI: 0.614, 0.979] Median Survival Benefit = 4.1 Mos.

  25. PROSTVAC-VF-Tricom A mixture of 2 viruses plus an altered protein Vaccinia Potent immunological priming agent Used in millions of immunizations Fowlpox Boosts the immune system Slightly altered PSA transgene Modified modified to be more immunogenic Tricom Lymphocyte function-associated antigen LFA-3 (CD58) Intercellular adhesion molecule ICAM-1 (CD54) Costimulatory molecule for the T-cell receptor B7.1 (CD80)

  26. PROSTVAC-PSA-Tricom PrimeBoosts Vaccinia-PSA-Tricom Fowlpox-PSA-Tricom

  27. Progression-Free Survival

  28. Overall Survival

  29. Future directions • Abiraterone- pre-surgery • Abiraterone phase III- no prior chemotherapy • Casodex and RAD001 • Ketoconazole/Hydrocortisone/Avodart/ Lapatinib • MDV3100 phase III post chemotherapy • Radiation +/- ipilimumab

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