1. STAMPEDE: Docetaxel Significantly Improves Survival in Men With Hormone-Naive Prostate Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from AstraZeneca, Bayer, Celgene Corporation, Genentech, Incyte, and Novartis.

2. STAMPEDE: Background
Since 1940s, prostate cancer mainly treated with hormone therapy
In early-stage pts (N0M0), addition of radiotherapy improves outcomes
Docetaxel prolongs survival in castration-refractory metastatic disease
Zoledronic acid mainly used to reduce skeletal metastases
Under investigation for metastasis prevention
Current study evaluated combination of zoledronic acid and docetaxel in early lines of therapy[1]
Evidence of synergy between these 2 agents[2]
Both well tolerated by most pts
1. James ND, et al. ASCO Abstract Ullén A, et al. Acta Oncol. 2005;44:

3. STAMPEDE: Study Design
Randomized, controlled, multiarm, multistage trial
Primary endpoint: OS
Secondary endpoints: FFS (PSA, local, or lymph node failure; distant metastases; prostate cancer death), toxicity, QoL, skeletal events, cost- effectiveness
Stratified by age, WHO stage,
metastases, previous treatments,
center, use of NSAIDS or aspirin
SOC
(n = 1184)
Dosage:
SOC: ADT ± RT
Zoledronic acid: 4 mg q3w to 18 wks, then q4w to 2 yrs
Docetaxel: 75 mg/m2 q3w for 6 cycles + prednisolone 10 mg QD
SOC + Zoledronic Acid
(n = 593)
WHO stage 0-2 pts with prostate cancer who have never received hormone therapy, fitting criteria based on stage of disease
(N = 2962)
SOC + Docetaxel
(n = 592)
ADT, androgen deprivation therapy; FFS, failure-free survival; NSAIDS, nonsteroidal antiinflammatory drugs; OS, overall survival; PSA, prostate-specific antigen; q3w, every 3 weeks; q4w, every 4 weeks; QD, once daily; QoL, quality of life; RT, radiotherapy; SOC, standard of care; WHO, World Health Organization.
SOC + Zoledronic Acid + Docetaxel
(n = 593)
James ND, et al. ASCO Abstract 5001.

4. STAMPEDE: Pt Characteristics
Baseline Characteristics
Characteristic
Pt Population
(N = 2962)
Median age, yrs (range)
65 (40-84)
WHO stage, %
PS 1
PS 2 21 1
Metastatic disease, %
N + M0
N0M0 61 15 24
Previous treatments, %
LHRL analogues
Radiotherapy
Local therapy 98 29 6
LHRL, luteinizing hormone-releasing hormone ; PS, performance status; WHO, World Health Organization.
James ND, et al. ASCO Abstract 5001.

5. STAMPEDE: Pt Inclusion Criteria
Inclusion criteria for all pts (≥ 1 of the following): metastatic disease, node positive, WHO PS 0-2
For newly diagnosed: ≥ 2 of the following: stage T3/T4, PSA ≥ 40 ng/mL, Gleason stage 8-10
For relapsed: PSA ≥ 20 ng/mL, PSA ≥ 4 ng/mL and rising with doubling time < 6 mos
PS, performance status; PSA, prostate-specific antigen; WHO, World Health Organization.
James ND, et al. ASCO Abstract 5001.

6. STAMPEDE: Significant Improvement in OS, FFS With Docetaxel + SOC vs SOC
Outcome
SOC + Docetaxel
(n = 592)
SOC
(n = 1184)
P Value
Median OS, mos (95% CI)
77 (70-NR)
67 (60-91)
Deaths, n
165
405
HR, survival (95% CI)
0.76 ( )
.003
Median FFS, mos (95% CI)
37 (33-42)
21 (18-24)
FFS events, n
371
750
HR, FFS (95% CI)
0.62 ( )
< 1 x 10-9
FFS, failure-free survival; NR, not reached; OS, overall survival; SOC, standard of care.
James ND, et al. ASCO Abstract 5001.

7. STAMPEDE: Significant Improvement in OS, FFS With Docetaxel, ZA, SOC vs SOC
Outcome
SOC + ZA + Docetaxel
(n = 592)
SOC
(n = 1184)
P Value
Median OS, mos (95% CI)
72 (63-90)
67 (60-91)
Deaths, n
181
405
HR, survival (95% CI)
0.81 ( )
.02
Median FFS, mos (95% CI)
37 (31-42)
21 (18-24)
FFS events, n
371
750
HR, FFS (95% CI)
0.62 ( )
< 1 x 10-9
FFS, failure-free survival; NR, not reached; OS, overall survival; SOC, standard of care; ZA, zoledronic acid.
James ND, et al. ASCO Abstract 5001.

8. STAMPEDE: No Significant Improvement in OS, FFS With ZA + SOC vs SOC
Outcome
SOC + Zoledronic Acid
(n = 593)
SOC
(n = 1184)
P Value
Median OS, mos (95% CI)
80 (70-NR)
67 (60-91)
Deaths, n
197
405
HR, Survival (95% CI)
0.93 ( )
.44
Median FFS, mos (95% CI)
21 (18-25)
21 (18-24)
No. of FFS events
371
750
HR, FFS (95% CI)
0.93 ( )
.26
FFS, failure-free survival; NR, not reached; OS, overall survival; SOC, standard of care, ZA, zoledronic acid.
James ND, et al. ASCO Abstract 5001.

9. STAMPEDE: Metastatic Analysis
Adding docetaxel to SOC showed significant improvement in OS in pts with M1 metastatic status (P = .002) but not M0 pts in preplanned analysis
Regimen (+ SOC)
Metastatic Status
Pts, n
OS Events
HR (95% CI) ZA M0
686 93
0.96 ( ) M1
1091
509
0.92 ( )
Overall
1777
602
0.93 ( )
DOC
689
1.01 ( )
1087
477
0.73 ( )
1776
570
0.76 ( )
ZA + DOC
687 91
1.03 ( )
1090
495
0.78 ( )
586
0.81 ( )
DOC, docetaxel; OS, overall survival; SOC, standard of care; ZA, zoledronic acid.
James ND, et al. ASCO Abstract 5001.

10. STAMPEDE: Adverse Events
Grade ≥ 3 AEs
SOC
(N = 1184)
SOC + ZA (n = 593)
SOC + Docetaxel
(n = 592)
SOC + ZA + Docetaxel
(n = 593)
Pts with AE data, n
1174
587
579
564
Any grade 3-5 AE, n (%)
363 (31)
185 (31)
291 (51)
294 (52)
Grade 5 AEs, n 3 1 7
Endocrine disorder, % 12 10
Febrile neutropenia, % 2
Neutropenia, % 11
Musculoskeletal disorders, % 5 6 8
Gastrointestinal disorders, %
Renal disorders 4
Grade ≥ 3 AEs at 1 yr, %
9.7
10.6
10.1
11.3
AE, adverse event; SOC, standard of care; ZA, zoledronic acid.
James ND, et al. ASCO Abstract 5001.

11. STAMPEDE: Conclusions
Addition of docetaxel to hormone therapy showed significant improvement in overall survival rate in pts with hormone-naive prostate cancer
Addition of zoledronic acid not associated with significant improvement in OS or FFS
Docetaxel therapy should be:
Considered for men with newly diagnosed metastatic prostate cancer
Selectively considered for men with high-risk nonmetastatic disease
FFS, failure-free survival; OS, overall survival.
James ND, et al. ASCO Abstract 5001.

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