Natural History of Prostate Cancer
Androgen deprivation
therapy (ADT)
Local
therapy
Hormone
sensitive
ADT
ADT +
Docetaxel in
high volume
disease?
Death
Therapies after
ADT
mCRPC
asymptomatic
(failed ADT)
mCRPC
mildly
symptomatic
mCRPC
symptomatic
mCRPC
postdocetaxel
Definition of CRPC 2014
Definition of CRPC 2013
EAU Guidelines – 2014 edition
EAU Guidelines – 2014 edition
Il processo di progressione tumorale nel
CaP
Totalmente dipendente da
testosterone circolante
Autoproduzione di
Testosterone
ADT
TARGET: CYP17
Attivazione di AR
aspecifica
Androgeno indipendente
AR indipendente
Mod. da Nelson et al, J Clin Oncol 2012
Enzalutamide Reduced Risk of Death by 29%
100
Hazard Ratio: 0.706 (95% CI:
0.60,0.84)
P<0.0001
90
80
Enzalutamide: 32.4
(95% CI 30.1, NYR)
Survival (%)
70
60
Placebo: 30.2 (95% CI 28.0, NYR)
50
40
30
Patients still alive at data cut off
Enzalutamide: 72%; Placebo: 63%
Enzalutamide: 241 deaths
Placebo: 299 deaths
20
Enzalutamide
Placebo
10
0
0
3
6
9
12
15
18
21
24
27
30
33
36
33
27
2
2
0
0
Duration of Overall Survival (Months)
Patients at Risk
Enzalutamid
e
Placeb
o
87
2
84
5
Median Follow-up 22 Months
863
835
850
781
824
744
797
701
745
644
566
484
395
328
244
213
128
102
Beer et al, N Engl J Med. 2014; 371(5):424-33
Final OS Analysis
•
•
Median follow-up of 49.2 months
Abiraterone treatment effect more pronounced when adjusting for 44% of prednisone
patients who received subsequent abiraterone (HR = 0.74)
Ryan C et al. ESMO 2014; Abstract 7530 (oral presentation)
Current Treatment Paradigm is Evolving
Androgen deprivation
therapy (ADT)
Local
therapy
Hormone
sensitive
Death
Therapies after
ADT
mCRPC
asymptomatic
(failed ADT)
mCRPC
mildly
symptomatic
mCRPC
symptomatic
mCRPC
postdocetaxel
ADT
Abiraterone
Abiraterone
ADT +
Docetaxel in
high volume
disease?
Enzalutamide
Enzalutamide
Radium 223
Docetaxel
Cabazitaxel
Sipuleucel-T
supportive care (eg
denosumab/bisphosphonates)