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PROSTATE CANCER

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11th Annual Symposium on Prostate Cancer Wednesday, September 23, 2009 Prevention Screening Detection Treatment Outline Developing Personalized Medicine ... – PowerPoint PPT presentation

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Title: PROSTATE CANCER


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
G43
G34
G33
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 individuals
    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
    (lt1ng/dl)
  • Androstenedione and DHEA lowered effectively in
    CRPC

15
Pre-docetaxel Phase I/II (n54)Maximal PSA
Declines after Abiraterone Monotherapy
38/54 PSA? 50 (70) 43/54 PSA? 30 (80)
16
Post-docetaxel Phase IIMaximal Change in PSA
(n34)
17/34 (50) pts 50 decline 22/34 (65) pts
30decline 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 lt12 weeks
N42 Chemo-naïve
gt50 Decline 23/42 (55)
21
PSA Declines at 12 Weeks for Post-Chemotherapy
Patients
5 pt off study lt12 weeks
N31 Post-chemo
gt50 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
Doctors Office
COMPLETE COURSE OF THERAPY Weeks 0, 2, 4
24
Provenge IMPACT Overall Survival Primary
Endpoint Intent-to-Treat Population
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
Vaccinia-PSA-Tricom
  • Prime Boosts

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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