This presentation describes how the treatment of stage 4 prostate cancer has improved over last 100 years. This was presented at URO ONCOLOGY UPDATE meeting of Delhi Urological Society on 18th March 2017

1. Changing Landscape in the Treatment of
Advanced Prostate Cancer
Dr Alok Gupta
MD, DM,
Consultant Medical Oncologist
Max Super Speciality Hospital, Saket
Ex-Asst. Professor, AIIMS, New Delhi

4. Metastatic Prostate Cancer
Changing Landscape
• 1940 - 2003
• 2015-2016
• 2004 - 2014

5. Cancer Res. 1941;293-297

6. Arch Surg. 1941;209-223

7. 75 YEARS LATER......
Androgen Deprivation therapy is still the
standard of care in metastatic hormone
sensitive prostate cancer

8. Survival in Metastatic Prostate Cancer in
Present Era

10. Mitoxantrone
Chemotherapy with mitoxantrone plus prednisone or
prednisone alone for symptomatic hormone-resistant
prostate cancer: a Canadian randomized trial with
palliative end points.
161 hormone-refractory patients
Primary end point was 2-point decrease in pain as assessed by a
6-point pain scale.
23 of 80 patients (29%) with Mito vs 10 of 81 patients (12%)
No overall survival difference.
J Clin Oncol 1996;14:1756-64.

11. • 242 patients with HRPC
• Randomized to receive either M+H or hydrocortisone alone.
• M+H:
– time to treatment failure
– disease progression
– QOL was better
• No difference in overall survival (12.3 months for M+H v 12.6
months for hydrocortisone alone
Mitoxantrone: CALGB B 9182 study
J Clin Oncol 1999; 17:2506-13.

12. Docetaxel: TAX327 and SWOG 9916

13. Median
survival Hazard
(mos) ratio P-value
Combined: 18.2 0.83 0.03
D 3 wkly: 18.9 0.76 0.009
D wkly: 17.3 0.91 0.3
Mitoxantrone 16.4 – –
Months
ProbabilityofSurviving
0 6 12 18 24 30
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Docetaxel 3 wkly
Docetaxel wkly
Mitoxantrone
Eisenberger M, et al. ASCO Annual Meeting Proceedings. June 2004. Abstract 4.
Docetaxel – CRPC
Overall Survival—TAX 327

14. Cabazitaxel
• Microtubule stabilizer
• Developed in docetaxel-
resistant prostate cancer cell
lines
• a favorable pharmacokinetic
and safety profile
• decreased propensity for P-
glycoprotein (Pgp)-mediated
drug resistance.
• inhibited cell growth in a wide
range of human cancer cell
lines, including tumor models
expressing Pgp.

15. TROPIC – Cabazitaxel vs Mitoxantrone
• CRPC
• PD during or
after
docetaxel
RANDOMIZE
Cabazitaxel 25 mg/m2 Q 21 d
Prednisone 10 mg daily
N=755
Mitoxantrone
Prednisone 10 mg daily
146 Sites /
26 Countries
Abbreviation: PD=progressive disease.
Source: deBono et al. Lancet. 2010;376:1147-1154.

16. TROPIC Primary Endpoint – OS
(ITT Analysis)
MP 377 300 188 67 11 1
CBZP 378 321 231 90 28 4
Number
at Risk
80
60
40
20
0
100
0 months 6 months 12 months 18 months 24 months 30 months
15.112.7Median OS (months)
0.59–0.8395% CI
<.0001P Value
0.70Hazard Ratio
CBZPMP
Abbreviation: ITT=intent-to-treat.
Source: deBono et al. Lancet. 2010;376:1147-1154.
ProportionofOS(%)

17. Most Frequent Grade ≥3
Treatment-Emergent AEs*
MP (n=371) CBZP (n=371)
All Grades (%) Grade ≥3 (%) All Grades (%) Grade ≥3 (%)
Any AE 88.4 39.4 95.7 57.4
Febrile neutropenia 1.3 1.3 7.5 7.5
Diarrhea 10.5 0.3 46.6 6.2
Fatigue 27.5 3 36.7 4.9
Asthenia 12.4 2.4 20.5 4.6
Back pain 12.1 3 16.2 3.8
Nausea 22.9 0.3 34.2 1.9
Vomiting 10.2 0 22.6 1.9
Hematuria 3.8 0.5 16.7 1.9
Abdominal pain 3.5 0 11.6 1.9
*Sorted by decreasing frequency of events grade ≥3 in the CBZP arm.
deBono et al. Lancet. 2010;376:1147-1154

18. Intratumoral Androgen Levels Are Increased Due To
Overexpression of The Androgen Synthetic Enzymes
Steroid content
Gerald et al, Amer J Pathol 164:217, 2004
LIVER
Positive control
Non-castrate
metastatic
Castrate
metastatic
Testosterone(ng/gm)
Prostate samples
( eugonadal)
Control and Metastatic autopsy
samples (castrate)
P1 P2 P3 P4 P5 P6 C1 C2 C3 M1 M2 M3 M4 M5 M6 M7 M8
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Primary prostate cancers
Metastatic prostate cancers
Control tissues (bladder, liver, lung)
Benign prostate
Testosterone
Montgomery et al. Cancer Res 68:4447, 2008
Squaline Monoxygenase

19. Targeting the Androgen Pathway
• Androgen Biosynthesis Inhibitors
– *Abiraterone Acetate
– TAK 700
– VN/124-1 (TOK-001)
• Novel Anti-Androgens
– *MDV3100
– RD 162
– EPI-001 (AR N-Terminal)
– SNARE-1 (selective nuclear receptor exporter-1)
* FDA approved

20. Abiraterone Acetate
Cholesterol
Pregnenolone Progesterone Corticosterone
17α-OH-
pregnenolone
DHEA Androstenedione Testosterone
17α –OH-
progesterone
Cortisol
CYP17
C17,20-lyase
CYP17
17α-hydroxylase
AldosteroneDeoxy-
corticosterone
DHT
5α-reductase
11-Deoxy-
cortisol
11β-
Hydroxylase
CYP19: aromatase
Estradiol
Desmolase
Renin
ACTH
+ Prednisone
Autocrine
and
paracrine
(adrenal)
pathways
X
X
Attard G, et al. JCO. 2008;26:4563-4571.

21. clinicaloptions.com/oncology
2011 Genitourinary Cancers Symposium: Highlights
COU-AA-301: Phase III Study of
Abiraterone Acetate in mCRPC
 Primary endpoint: OS
 Abiraterone acetate: selective inhibitor of androgen
biosynthesis that blocks CYP17 activity
Patients with mCRPC
progressing after 1-2
chemotherapy regimens,
1 of which contained
docetaxel
(N = 1195)
Abiraterone acetate 1000 mg/day +
Prednisone 5 mg BID
(n = 797)
Placebo +
Prednisone 5 mg BID
(n = 398)
Stratified by ECOG PS, worst pain over previous
24 hrs, previous chemotherapy, type of progression
Scher HI, et al. ASCO GU 2011. Abstract 4.
Randomized 2:1
Study stopped at planned interim analysis at 534 events because
OS improvement crossed predetermined stopping boundary

22. clinicaloptions.com/oncology
2011 Genitourinary Cancers Symposium: Highlights
COU-AA-301: Overall Survival
 Abiraterone acetate significantly improved OS vs placebo
– Survival benefit consistent across nearly all patient subgroups
Group n HR (95% CI)
Baseline ECOG 0-1 1068 0.64 (0.53-0.78)
BPI
 < 4 659 0.64 (0.50-0.82)
 ≥ 4 536 0.68 (0.53-0.85)
Prior chemotherapy
 1 regimen 833 0.63 (0.51-0.78)
 2 regimens 362 0.74 (0.55-0.99)
Progression type
 PSA only 363 0.59 (0.42-0.82)
 Radiographic 832 0.69 (0.56-0.84)
Visceral disease 363 0.70 (0.52-0.94)
Scher HI, et al. ASCO GU 2011. Abstract 4.
AA Placebo
HR: 0.646 (95% CI: 0.54-0.77; P < .0001)
Survival(%)
100
80
60
40
20
0
0 3 6 9 12 15 18 21
Mos to Death
Placebo:
10.9 mos (95% CI: 10.2-12.0)
Abiraterone acetate:
14.8 mos (95% CI: 14.1-15.4)
AA
Placebo
797
398
736
355
657
306
520
210
282
105
68
30
2
3
0
0

23. clinicaloptions.com/oncology
2011 Genitourinary Cancers Symposium: Highlights
COU-AA-301: Safety
 Overall incidence of AEs similar between arms
– Slight increase in fluid retention, hypokalemia, and cardiac
disorders observed with abiraterone, but events primarily
mild/moderate in severity
Treatment-Related AEs, % Abiraterone Acetate
(n = 791)
Placebo
(n = 394)
All Grades Grade 3/4 All Grades Grade 3/4
All treatment-related AEs 99 55 99 58
Fluid retention 31 2 22 1
Hypokalemia 17 3 8 1
Cardiac disorders* 13 3 11 2
Hypertension 10 1 8 < 1
LFT abnormalities 10 3 8 3
Scher HI, et al. ASCO GU 2011. Abstract 4.
*Most frequent cardiac disorders were tachycardia and atrial fibrillation.

24. Overall Study Design of COU-AA-302
• Phase 3 multicenter, randomized, double-blind, placebo-controlled study conducted
at 151 sites in 12 countries; USA, Europe, Australia, Canada
• Stratification by ECOG performance status 0 vs 1
AA 1000 mg daily
Prednisone 5 mg BID
(Actual n = 546)
Co-Primary:
• rPFS by central review
• OS
Secondary:
• Time to opiate use
(cancer-related pain)
• Time to initiation of
chemotherapy
• Time to ECOG-PS
deterioration
• TTPP
Efficacy end points
Placebo daily
Prednisone 5 mg BID
(Actual n = 542)
R
A
N
D
O
M
I
Z
E
D
1:1
• Progressive chemo-
naïve mCRPC
patients
(Planned N = 1088)
• Asymptomatic or
mildly symptomatic
Patients
Ryan et al. ASCO 2012

25. Statistically Significant Improvement in rPFS
Primary End Point
NR, not reached; PL, placebo.
Data cutoff 12/20/2010.
100
80
60
40
20
0
0
Progression-Free(%)
3 6 9 15 1812
546
542
489
400
340
204
164
90
12
3
0
0
AA
PL
46
30
Time to Progression or Death (Months)
AA + P
PL + P
AA + P (median, mos): NR
PL + P (median, mos): 8.3
HR (95% CI): 0.43 (0.35-0.52)
P value: < 0.0001
Ryan et al. ASCO 2012

26. Strong Trend in OS Primary End Point
546
542
538
534
482
465
452
437
27
25
0
0
524
509
503
493
0
2
120
106
258
237
412
387
100
80
60
40
20
0
0
Survival(%)
3 12 15 27
Time to Death (Months)
33
AA + P
PL + P
6 9 30242118
AA
PL
AA + P (median, mos): NR
PL + P (median, mos): 27.2
HR (95% CI): 0.75 (0.61-0.93)
P value: 0.0097
Updated GU ASCO 2013: Rathkopf et al. Abstract # 5
-r PFS 16.5 vs. 8.3 mo. HR 0.53 (0.45-0.62) p = <0.0001
- OS 35.3 vs. 30.1 mo. HR 0.79 (0.66-0.96) p= 0.0151

27. Prostate Cancer:
“Adapting” to castrate environment
ALTERN.
SPLICING
ABERRANT
MODIFICATION
•GF, cytokines
•Src
Sumo
AC
P
COFACTOR
PERTURBATION
•CoAct gain
•CoR loss/dismissal
CoACT
INTRACRINE
ANDROGEN
SYNTHESIS
T
MUTATION
•gain of function
AR
selective
pressure
Hormone Therapy
adaptation
RECURRENT TUMOR DEVELOPMENT
CRPC
RESTORED AR ACTIVITY
(rising PSA)
>30% CRPC
AR
DEREGULATION
•amplification
•overexpression
Penning & Knudsen
2010

28. Understanding the Biology of CRPC
Driver Pathways of Dependency of PC
Tomlins, S. A. Eur Urol 2009
Taylor, B et al, Cancer Cell 2010
Kong D. Cancer Sci 2008
Jenkins, R. B. Cancer Res 1997
Khor, L. Y. Clin Cancer Res 2007
Androgen Receptor (AR) 55% 100%
PTEN loss 25% 80%
PI3K/Akt, Ras/Raf, RB 42% 100%
TMPRSS2-ETS fusion 50% 33%
Genetic variants of androgen transporter genes
Primary Mets

29. clinicaloptions.com/oncology
2012 Genitourinary Cancers Symposium: Highlights
Scher HI, et al. ASCO GU 2012. Abstract LBA1.
Patients with progressive
CRPC who failed docetaxel
chemotherapy
(N = 1199)
 Primary endpoint: OS
 Secondary endpoints:
– Response: PSA response, STOR, QoL, pain palliation, CTC
– Progression: radiographic PFS, time to PSA progression, time to first SRE
Randomized 2:1
Stratified by ECOG PS and Mean Brief
Pain Inventory question 3 score
MDV3100 160 mg/day
(n = 800)
Placebo
(n = 399)
Study stopped at planned interim analysis at
520 events with observation of statistically
significant, clinically meaningful OS benefit
AFFIRM: Phase III Trial of MDV3100 in
Post-Docetaxel CRPC

30. clinicaloptions.com/oncology
2012 Genitourinary Cancers Symposium: Highlights
Scher HI, et al. ASCO GU 2012. Abstract LBA1.
 OS improved with MDV3100 vs placebo
 Median follow-up: 14.4 mos
AFFIRM Trial of MDV3100 in Post-
Docetaxel CRPC: OS
HR: 0.631 (95% CI: 0.529-0.752; P < .0001)
37% reduction in risk of death
Placebo: 13.6 mos
(95% CI: 11.3-15.8)
MDV3100: 18.4 mos
(95% CI: 17.3-NR)
Duration of OS (Mos)
0 3 6 9 12 15 18 21 24
Survival(%)
0
10
20
30
40
50
60
70
80
90
100
MOV3100
Placebo
800
399
775
376
701
317
627
263
400
167
211
81
72
33
7
3
0
0

31. clinicaloptions.com/oncology
2012 Genitourinary Cancers Symposium: Highlights
Scher HI, et al. ASCO GU 2012. Abstract LBA1.
 Secondary outcomes support survival benefit
Response, % MDV3100
(n = 800)
Placebo
(n = 399)
P Value
PSA decline
 ≥ 50% from baseline 54.0 1.5 < .0001
 ≥ 90% from baseline 24.8 0.9 < .0001
STOR by CT/MRI 28.9 3.8 < .0001
Progression, Mos MDV3100
(n = 800)
Placebo
(n = 399)
HR
(95% CI; P Value)
Median time to PSA
progression
8.3 3.0 0.0248
(0.204-0.303; < .0001)
Median radiographic PFS 8.3 2.9 0.404
(0.350-0.466; < .0001)
AFFIRM Trial of MDV3100 in Post-
Docetaxel CRPC: Secondary Outcomes

32. clinicaloptions.com/oncology
2012 Genitourinary Cancers Symposium: Highlights
Scher HI, et al. ASCO GU 2012. Abstract LBA1.
Treatment-Related AEs, % All Grades Grade ≥ 3 Events
MDV3100
(n = 800)
Placebo
(n = 399)
MDV3100
(n = 800)
Placebo
(n = 399)
All AEs 98.1 97.7 45.3 53.1
All serious AEs 33.5 38.6 28.4 33.6
Fatigue 33.6 29.1 6.3 7.3
Cardiac disorders 6.1 7.5 0.9 2.0
 Myocardial infarction 0.3 0.5 0.3 0.5
LFT abnormalities 1.0 1.5 0.4 0.8
Seizure* 0.6 0 0.6 0
 Adverse event rates similar for MDV3100 and placebo, despite longer reporting
period for MDV3100
 No on-treatment patient deaths
*2 of 5 patients experiencing seizure on MDV3100 were found to have brain metastases; 1 was receiving
IV lidocaine for biopsy.
AFFIRM Trial of MDV3100 in Post-
Docetaxel CRPC: Toxicity

33. clinicaloptions.com/oncology
Change Folio Title on Master /Arial 15pt /Unbold White
clinicaloptions.com/oncology
2014 Genitourinary Cancers Symposium
PREVAIL Phase III Trial: Enzalutamide
After Progression in mCRPC
Beer T, et al. ASCO GU 2014. Abstract 1. ClinicalTrials.gov. NCT01212991.
Patients with
progressive mCRPC,
asymptomatic/mildly
symptomatic,
chemotherapy naive,
steroids allowed
(N = 1717)
Enzalutamide
160 mg/day
(n = 872)
Placebo
(n = 845)
 Primary endpoints: OS, radiographic PFS

34. clinicaloptions.com/oncology
Change Folio Title on Master /Arial 15pt /Unbold White
clinicaloptions.com/oncology
2014 Genitourinary Cancers Symposium
PREVAIL Study of Enzalutamide in
mCRPC: OS and Radiographic PFS
Beer T, et al. ASCO GU 2014. Abstract 1.
Median Radiographic PFS,
Mos (95% CI)
Median OS,
Mos (95% CI)
Enzalutamide Placebo Enzalutamide Placebo
NR
(13.8-NR)
3.9
(3.7-5.4)
32.4
(30.1-NR)
30.2
(28.0-NR)
HR: 0.706 (0.60-0.84; P < .0001) HR: 0.186 (0.15-0.23; P < .0001)
 Risk of death reduced 29% with enzalutamide
 Consistent survival benefit across subgroups
 Trial halted and unblinded after data and safety monitoring committee
reported statistically significant benefits in OS and radiographic PFS
with enzalutamide

35. Therapies With Survival Benefit for
mCRPC
Agent Indication
Route
Schedule
Cortico-
steroids
Symptoms
Contra-
indications
PSA
Response
Median OS
Benefit,
Mos
Sipuleucel-T
pre/post
docetaxel
IV every 2
wk x 3
no
asymptomatic,
minimally sx
narcotics for
pain, liver
mets
no 4.1
Abiraterone pre/post
docetaxel
oral, empty
stomach
yes* not specified
severe liver
dysfx, low K,
heart failure
yes
Post-doc:
4.6
Pre-doc: 4.4
Enzalutamide pre/post
docetaxel
oral no not specified seizures yes
Post-doc:
4.8
Pre-doc: 4.0
Docetaxel mCRPC
IV every 3
wk
yes* not specified
moderate
liver dysfx,
cytopenias
yes 2.4
Cabazitaxel
post
docetaxel
IV every 3
wk
yes* not specified
moderate
liver dysfx,
cytopenias
yes 2.4
Radium-223
post
docetaxel
or not fit
for doc
IV, every 4
wks for 6
doses
not
required
symptomatic
bone
metastases
visceral
mets
NR 3.6
* In clinical trials and on FDA label.

36. • With all these agents approved where do we
stand in terms of overall survival in metastatic
prostate cancer?
2014

37. Survival in Metastatic Prostate Cancer in
Present Era

38. ADT plus docetaxel greater tumor
regression
AR independent clones
AR dependent clones
ADT + Docetaxel

39. clinicaloptions.com/oncology
2011 Genitourinary Cancers Symposium: Highlights
Addition of Docetaxel to ADT in Pts With
Metastatic PC: Phase III GETUG 15 Study[1]
 Primary endpoint: 3-yr OS
 Secondary endpoints: biological and clinical PFS, QoL, toxicity
1. Gravis G, et al. ASCO GU 2011. Abstract 10.
2. Glass TR, et al. J Urol. 2003;169:164-169.
Patients with hormone-
naive metastatic prostate
cancer and ECOG
performance score 0-2
(N = 385)
Docetaxel 75 mg/m2 Q3W for 9 cycles +
ADT*
(n = 192)
ADT*
(n = 193)
Stratified by previous systemic therapy,
Glass risk group[2]
*ADT: LHRH agonist, maximum androgen blockade, or orchiectomy

40. Median Follow up : 50 m
ADT plus docetaxel: 58·9 m
ADT: 54·2 m
(HR1·01, 95% CI 0·75–1·36)

41. CHAARTED Trial

42. CHAARTED: Study Design
 Randomized phase III trial
Metastatic hormone-
sensitive prostate cancer
with elevated PSA, ECOG
PS 0-2, no prior docetaxel
(N = 790)
ADT + Docetaxel
75 mg/m2 Q3W
up to 6 cycles
(n = 397)
ADT alone
(n = 393)
Stratified by extent of mets (high vs low); age (≥ 70 vs < 70 yrs); ECOG
PS (0-1 vs 2); CAB > 30 days (yes vs no); SRE prevention (yes vs no),
prior adjuvant ADT (≤ 12 vs > 12 mos)

43. Median follow up : 28.9 months

48. Survival in Metastatic Prostate Cancer
in Present Era

50. Feasibilty of administering Docetaxel
 Combination arm
– 86% completed six cycles of docetaxel
– 74% without dose modifications
 ADT arm at progression
– 287 patients – CRPC
– Only 147 could receive docetaxel

52. clinicaloptions.com/oncology
STAMPEDE: Docetaxel Significantly Improves Survival in Prostate Cancer
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
WHO stage 0-2 pts
with prostate cancer
who have never
received hormone
therapy, fitting
criteria based on
stage of disease
(N = 2962)
SOC
(n = 1184)
SOC + Docetaxel
(n = 592)
SOC + Zoledronic Acid
(n = 593)
SOC + Zoledronic Acid + Docetaxel
(n = 593)
James ND, et al. ASCO 2015. Abstract 5001.
Stratified by age, WHO stage,
metastases, previous treatments,
center, use of NSAIDS or aspirin
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

53. clinicaloptions.com/oncology
Genitourinary Cancers
STAMPEDE: OS, FFS With Docetaxel +
SOC vs SOC
Outcome
SOC +
Doc
(n = 592)
SOC
(n = 1184)
P
Value
Deaths, n 165 405
HR, survival
(95% CI)
0.76 (0.63-0.91) .003
Median FFS,
mos (95% CI)
37 (33-42) 21 (18-24)
FFS events, n 371 750
HR, FFS
(95% CI)
0.62 (0.54-0.70)
< 1 x
10-9
James ND, et al. ASCO 2015. Abstract 5001. Reprinted with permission.
Mos From Randomization
0 8412 24 36 48 60 72
1.0
0.8
0.6
0.4
0.2
0
ProbabilityofOS
Median OS (95% CI)
SOC 67 mos (60-91)
SOC + Doc 77 mos (70-NR)

54. STAMPEDE: OS for Pts with Metastatic
Disease
Median OS (IQR)
SOC 45 mos (23, 91), 350 deaths
SOC+Doc 60 mos (27, 103), 144 deaths
HR (95%CI): 0.76 (0.62, 0.92)
P value 0.005
James ND, et al. Lancet. 2016;387:1163-1177.

55. clinicaloptions.com/oncology
Genitourinary Cancers
STAMPEDE: Adverse Events
Grade ≥ 3 AEs SOC
(N = 1184)
SOC + ZA
(n = 593)
SOC +
Doc
(n = 592)
SOC + ZA +
Doc
(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 3 7
Endocrine disorder, % 12 12 10 12
Febrile neutropenia, % 1 2 12 12
Neutropenia, % 1 1 12 11
Musculoskeletal disorders, % 5 5 6 8
Gastrointestinal disorders, % 3 3 7 7
Renal disorders, % 5 4 4 6
Grade ≥ 3 AEs at 1 yr, % 9.7 10.6 10.1 11.3
James ND, et al. ASCO 2015. Abstract 5001.

56. Docetaxel in Hormone sensitive
prostate cancer
Study Accrual
Years
Treatment Arms N OS HR (95% CI)
[months]
GETUG 15 2004-
2008
• ADT
• ADT + D 75 mg/m2 max 9
cycles
385 1.01 (0.75-1.36)
[54.2 vs 58.9]
CHAARTED
(E3805)
2006-
2012
• ADT
• ADT + D 75 mg/m2 max 6
cycles
790 0.61 (0.47-0.80)
[44.0 vs 57.6]
STAMPEDE 2005-
2013
• ADT
• ADT + D 75 mg/m2 max 6
cycles + Pred 10mg daily
• ADT + D 75 mg/m2 max 6
cycles + ZA 4 mg + Pred 10
mg daily
1817* 0.76 (0.62-0.92)
[45 vs 60]
0.79 (0.66 v 0.96)
[45 vs 55]
*M1 disease only. Gravis G, et al. Lancet Oncol. 2013;14:149-158.
Gravis G, et al. Eur Urol. 2015;[Epub ahead of print].
Sweeney CJ, et al. N Engl J Med. 2015;373:737-746.
James ND, et al. Lancet. 2016;387:1163-1177.

57. STOpCaP
Addition of docetaxel or bisphosphonates to
standard of care in men with localised or metastatic,
hormone-sensitive prostate cancer: a systematic
review and meta-analyses of aggregate data
Vale CL, Burdett S, Rydezewska LH, Albiges L, Clarke NW, Fisher D,
Fizazi K, Gravis G, James ND, Mason MD, Parmar MKB, Sweeney CJ,
Sydes MR, Tombal B, Tierney JF, for the STOpCaP steering group
The Lancet Oncology, Volume 17, Issue 2, February 2016, Pages 243-256
doi:10.1016/S1470-2045(15)00489-1

58. STOpCaP: Meta-analysis of OS
Vale CL, et al. Lancet Oncol. 2016;17:243-256.

59. Summary
 The value of docetaxel added to ADT for mHSPC is
clearly established
– …but patient selection for appropriateness of
chemotherapy is imperative.

61. Conclusions
• 1940 – 2003
• “Era of ADT”
• 2015-2016
• “Era of
sequencing”
• 2004 – 2014
• “Era of Discovery”

62. Thank You
Dr Alok Gupta MD, DM,
Consultant Medical Oncologist
Max Super Speciality Hospital, Saket
Phone No. 9167164364
Email: alokgupta16@yahoo.co.in