Impact of node status and radiotherapy on

failure-free survival in patients with newly-diagnosed

non-metastatic prostate cancer: v
Data from >690 patients in the control arm of the
STAMPEDE trial (MRC PR08, CRUK/06/019)

Nicholas James on behalf of:
MR Spears, NW Clarke, MR Sydes, CC Parker, DP Dearnaley,
JM Russell, AWS Ritchie, G Thalmann, JS De Bono, G Attard,
C Amos, MK Parmar, MD Mason and the STAMPEDE Investigators
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STAMPEDE
Recruits men from 4 groups starting long-term ADT:
1. High-risk localised (T3/4, PSA >40 or Gleason 8-10)
2. Node-positive (N+) prostate cancer
3. Newly-diagnosed metastatic (M1)
4. High risk recurrence post surgery or RT
Tests addition of further treatments to standard care
Radical radiotherapy in standard care:
N+M0 patients; optional
N0M0 patients; optional Oct 2005 Nov 2011, mandatory
from Nov-2011



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www.stampedetrial.org
STAMPEDE
Recruits men from 4 groups starting long-term ADT:
1. High-risk localised (T3/4, PSA >40 or Gleason 8-10)
2. Node-positive (N+) prostate cancer
3. Newly-diagnosed metastatic (M1)
4. High risk recurrence post surgery or RT
Tests addition of further treatments to standard care
Radical radiotherapy in standard care:
N+M0 patients; optional
N0M0 patients; optional Oct 2005 Nov 2011, mandatory
from Nov-2011



3
www.stampedetrial.org
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[A]+zoledronic acid
[A]+docetaxel
[A]+celecoxib
[A]+ZA+docetaxel
[A]+ZA+celecoxib
[A]+(abi)*
ADT (+/-RT) [CTRL]
[A]+M1|RT {M1}
[A]+(enza+abi)**
* Abiraterone
** Enzalutamide + abiraterone
Accrual - past
Accrual - future
Follow-up
A
B
C
D
E
F
G
H
J
A
B
C
D
E
F
G
H
J
T
r
i
a
l

a
r
m
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Jul-2014: Third new comparison

STAMPEDE: Enzalutamide + abiraterone comparison activated
[A]+zoledronic acid
[A]+docetaxel
[A]+celecoxib
[A]+ZA+docetaxel
[A]+ZA+celecoxib
[A]+(abi)*
ADT (+/-RT) [CTRL]
[A]+M1|RT {M1}
[A]+(enza+abi)**
* Abiraterone
** Enzalutamide + abiraterone
Accrual - past
Accrual - future
Follow-up
A
B
C
D
E
F
G
H
J
A
B
C
D
E
F
G
H
J
T
r
i
a
l

a
r
m
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Jul-2014: Third new comparison

STAMPEDE: Enzalutamide + abiraterone comparison activated
5
6
[A]+zoledronic acid
[A]+docetaxel
[A]+celecoxib
[A]+ZA+docetaxel
[A]+ZA+celecoxib
[A]+(abi)*
ADT (+/-RT) [CTRL]
[A]+M1|RT {M1}
[A]+(enza+abi)**
* Abiraterone
** Enzalutamide + abiraterone
Accrual - past
Accrual - future
Follow-up
A
B
C
D
E
F
G
H
J
A
B
C
D
E
F
G
H
J
T
r
i
a
l

a
r
m
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Jul-2014: Third new comparison

STAMPEDE: Enzalutamide + abiraterone comparison activated
Aims
1. Describe prognosis for men with newly-diagnosed
high-risk M0 disease
2. Describe impact of planned radical RT on time to
progression
split by nodal status

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Primary outcome measures
Overall survival [definitive]
Time from randomisation to death from any cause

Failure-free survival (FFS) [intermediate]
Time from randomisation to evidence of at least one of:
Biochemical failure
Progression: local, lymph nodes, distant metastases
Death from prostate cancer

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Methods
Database frozen 01-May-2014
Cox models to look at effects by node status subgroups
Models adjusted for other prognostic factors:
Age at randomisation (<60, 60-64, 65-69, 70 years)
Log-transformed pre-ADT PSA (continuous)
WHO performance status (0 vs 1&2)
Initial Gleason sum score category (7, 8, unknown)
Subgroup analyses looked at regional lymph nodes
N0 randomised <15-Nov-2011
N+ randomised >1 year prior to data freeze

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Results Aim 1
Prognosis of newly-diagnosed high-risk M0 disease
Cohort selection:

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Allocated to control arm
N=1858
Allocated to research arms
N=3,715
Non-metastatic
N=788
Metastatic
N=1090
Randomised by 01-May-2014
N=5,573
Diagnosed within 6m
pre-randomisation
N=721
Diagnosed more than 6m
pre-randomisation
N=67

Newly-diagnosed M0 patients
(randomised Oct-2005 to May-2014)
Number of patients 721
Median Age (years) 66 (61-77)
Median PSA pre ADT (ng/mL) 43 (IQR 18-88)
Node-positive 40% (n=287/721)
Gleason summary score 8-10 74% (n=535/721)
WHO Performance Status 1-2 15% (n=110/721)
Planned for RT 75% (n=539/721)
Median follow-up (months) 17 (IQR 6-36)
FFS events 149
Deaths 40
M0 cohort demographics
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63.3 (IQR 26.4-NR)
0.00
0.25
0.50
0.75
1.00
P
r
o
p
o
r
t
i
o
n

e
v
e
n
t
-
f
r
e
e
721 392 (7) 273 (10) 173 (6) 108 (6) 46 (9) 24 (2) 8 (0) Death
721 345 (74) 219 (32) 128 (18) 69 (14) 35 (6) 18 (3) 3 (2) FFS Event
N(risk)
0 12 24 36 48 60 72 84
Time from randomisation (Months)
FFS Event Death
Survival & FFS outcomes M0 cohort
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RT in high-risk M0 prostate cancer
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Adding RT to androgen deprivation therapy (ADT)
reduces risk of death (by about 50%)
SPCG7 - node-negative (N0) & largely at lower end of risk
spectrum (max PSA 80)
PR07 - no mandatory nodal staging, but only for N0 if done;
no PSA cap
Uncertainty about role of RT in pts with:
N0 PSA>80 disease
N+ disease
No RCT of RT in N+M0 patients


RT recommended schedules
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Trial patient intended for standard (M0)
RT on arms ABCDEFG
N0 N+
Prostate: 74Gy/37f
Pelvis: 46Gy/23f to 50Gy/25f
Or equivalent schedule
Prostate: 74Gy/37f
Or equivalent schedule
Whole pelvis +
prostate boost
RT to prostate only +/-
seminal vesicles
Prostate: 74Gy/37f
Pelvis: ~55Gy/37f
Or equivalent schedule
Clinical
choice
Clinical
choice
Results Aim 2
Impact of planned RT on time to progression

Split by nodal status:
N0 randomised prior to 15-Nov-2011
N+ randomised at least 1 year prior to data freeze

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Nodal subgroups
Data frozen
01-May-2014

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FFS
Events
N=21
FFS
Events
N=30
FFS
Events
N=27
FFS
Events
N=40
RT not
planned
N=59
RT
planned
N=121
RT not
planned
N=80
RT
planned
N=98
Randomised >1yr ago
N=178
Randomised <15/11/2011
N=180
Nodal stage unknown
N=1
N+
N=287
N0
N=433
Diagnosed within 6m
pre-randomisation
N=721
Nodal subgroup demographics
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Node-negative pts
(rand <15-Nov-2011)
Node-positive pts
(randomised >1 year)
Number of patients 180 178
Median Age (years) 66 (IQR 60-71) 65 (IQR 60-70)
Median PSA pre-ADT (ng/mL) 26 (IQR 58-104) 35 (IQR 15-76)
Gleason summary score 8-10 75% (n=135/180) 75% (n=133/178)
WHO Performance Status 1-2 11% (n=19/180) 13% (n=24/178)
Planned for RT 67% (n=121/180) 55% (n=98/178)
Median follow-up (months) 46 (IQR 35-59) 27 (IQR 19-45)
FFS events 51 67
Deaths 16 22
FFS by RT status: Node-negative cohort
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62% (95% CI 48-73)
87% (95% CI 79-92)
0.00
0.25
0.50
0.75
1.00
121 112 (5) 101 (3) 61 (6) 37 (5) 19 (2) 8 (0) 0 (0) +RT
59 48 (11) 39 (8) 29 (3) 13 (4) 4 (3) 2 (1) 2 (0) -RT
N(risk)
0 12 24 36 48 60 72 84
Time from randomisation (months)
-RT +RT
N0 Planned radical RT status
62% (95% CI 48-73)
87% (95% CI 79-92)
0.00
0.25
0.50
0.75
1.00
121 112 (5) 101 (3) 61 (6) 37 (5) 19 (2) 8 (0) 0 (0) +RT
59 48 (11) 39 (8) 29 (3) 13 (4) 4 (3) 2 (1) 2 (0) -RT
N(risk)
0 12 24 36 48 60 72 84
Time from randomisation (months)
-RT +RT
N0 Planned radical RT status
FFS by RT status: Node-negative cohort
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HR 0.33
(95% CI 0.18-0.61)
Note landmark analysis of patients FFS event-free at 6m = same
47% (95% CI 33-59)
71% (95% CI 58-81)
0.00
0.25
0.50
0.75
1.00
98 75 (14) 42 (4) 23 (4) 10 (2) 7 (1) 4 (2) 0 (0) +RT
80 54 (18) 29 (13) 15 (4) 9 (3) 5 (0) 4 (0) 1 (2) -RT
N(risk)
0 12 24 36 48 60 72 84
Time from randomisation (months)
-RT +RT
N+ Planned radical RT status
FFS by RT status: Node-positive cohort
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47% (95% CI 33-59)
71% (95% CI 58-81)
0.00
0.25
0.50
0.75
1.00
98 75 (14) 42 (4) 23 (4) 10 (2) 7 (1) 4 (2) 0 (0) +RT
80 54 (18) 29 (13) 15 (4) 9 (3) 5 (0) 4 (0) 1 (2) -RT
N(risk)
0 12 24 36 48 60 72 84
Time from randomisation (months)
-RT +RT
N+ Planned radical RT status
FFS by RT status: Node-positive cohort
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HR 0.51
(95% CI 0.31-0.84)
Note landmark analysis of patients FFS event-free at 6m = same
Survival better than anticipated at trial inception in 2005
In M0, control arm patients overall 63.3m

Effect of RT in N0M0 patients consistent with effect seen
in previous large RCTs

Effect of RT in N+ patients similar to effect in N0 patients

Strongly supports routine use RT in node-positive
prostate cancer
Conclusions
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Acknowledgements
Funding:
Cancer Research UK (CRUK/016/09)
Novartis; free drug & educational grant
Sanofi-Aventis; discounted drug & educational grant
Pfizer; free drug & educational grant
Janssen; free drug & educational grant
Astellas; free drug & educational grant
Medical Research Council; core funding
All clinicians and hospital staff who have supported, and
continue to support, the trial
All patients, who have joined the trial, and their families
Slides available via @Prof_Nick_James
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Thanks to all
investigators +
site staff, IDMC,
and TSC