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1. New in Management of Metastatic Hormone
Sensitive Prostate Cancer
Dr Alok Gupta
MD, DM,
Consultant Uro-Medical Oncologist
Max Super Speciality Hospital, Saket
Ex-Asst. Professor, AIIMS, New Delhi

2. Metastatic Prostate Cancer
Changing Landscape
 1940 – 2003
 Era of ADT
 2015-2017
 Era of
sequencing
• 2004 – 2014
• Era of
Discovery
Cancer Res. 1941;293-297

4. Survival in Metastatic Prostate Cancer in 2014

5. Metastatic Prostate Cancer
Changing Landscape
 2015-2018
 Era of
sequencing

6. 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

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

8. CHAARTED Trial

9. 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)

10. Median follow up : 28.9 months

11. CHAARTED: OS by Disease Volume
Sweeney CJ, et al. N Engl J Med. 2015;373:737-746.

13. 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

14. 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.

15. 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.

16. Survival in Metastatic Prostate Cancer
in Present Era

17. Title: 2 weekly Docetaxel in Newly Diagnosed High Volume
Metastatic Castration Naïve Prostate Cancer
Shaik Maheboob Hussain1, Gagan Gautam2, Puneet Ahluwalia2,
Harit Chaturvedi2, Anirudh Punnakal3, Alok Gupta1
1 Department of Medical Oncology,
2 Department of Surgical Oncology,
3 Department of Radiation Oncology,
Max Institute of Cancer Care, Max Super Speciality Hospital, Saket, New Delhi

18. Aim
 To determine toxicity and efficacy of 2-weekly
Docetaxel in high volume metastatic Castration
Naïve Prostate Cancer patients.

19. Characteristics Number 20 (100 %)
Age (years)
Median 64
Range 41-75
ECOG PS
0-1 18 (90)
≥2 2 (10)
Volume of Disease
High 20
Low 0
Bone metastasis (%) 19 (95)
Lymph node metastasis (%) 19 (95)
Visceral metastasis (%) 5 (25)
Gleason score
<7 0
7 6 (30)
8-10 14 (70)
Baseline PSA (ng/ml)
Median 105
Range 3.8-4000
Prior Treatment for Prostate Cancer
No Local Therapy 19 (95)
Primary Radiation 0
Prostatectomy 1 (5)
Androgen Deprivation Therapy
GnRH Agonist 9 (45)
GnRH Antagonist 9 (45)
Total Androgen Blockade 0
Surgical Castration 2 (10)
Table 1: Baseline characteristics of Patients

20. Serological CR (PSA <0.2 ng/ml)
Achieved
Not Achieved
55% 45%

21. At Risk
PSA ≤ 0.2 ng/ml 453 210 63
0.2 < PSA ≤ 4.0 219 77 20
PSA > 4.0 92 17 7
On therapy: PSA decline at 7 months identifies
those destined for longer response to ADT
Hussain et al. J Clin Oncol, 2006

22. Outcome measure Our Study CHAARTED Trial
Serological CR Achieved 45% (N=9) 32%
Time to Serological CR
Median 5 months -
Range 1-10 months -
Table 2: Comparison of Serological CR (PSA<0.2 ng/ml) with
CHAARTED Trial

23. Table 3: Analysis of Potential Factors associated with achievement of
Serological CR (PSA<0.2 ng/ml)
Factor Serological CR No Serological CR P value
Age
<64 5 7 1
>64 4 4
ECOG PS
0-1 8 10 1
≥2 1 1
Visceral
Metastasis
Yes 3 2 0.62
No 6 9
Gleason
≤7 3 3 1
8-10 6 8
PSA (ng/ml)
≤100 5 5 1
>100 4 6
ADT type
GnRH Agonist 5 4 0.64
GnRH Antagonist 3 6

24. Grade 3-5 Adverse Events
Our Study
CHAARTED Trial
30%
15%

25. Table 4: Comparison of grade 3-5 adverse events to CHAARTED Trial
Grade 3-5 Adverse Events CHAARTED Trial (%) Our study (%)
Allergic Reaction 8 (2.1) 0
Fatigue 16 (4.1) 0
Diarrhea 4 (1) 0
Stomatitis 2 (0.5) 0
Sensory neuropathy 2 (0.5) 0
Motor neuropathy 2 (0.5) 0
Thromboembolism 3 (0.8) 0
Anemia 5 (1.3) 0
Thrombocytopenia 1 (0.3) 0
Neutropenia 47 (12.1) 0
Febrile neutropenia 24 (6.1) 0
Infection with neutropenia 9 (2.3) 0
Paronychia NA 2 (10)
Death 1 (0.3) 1 (5)
Any event 114 (29.3) 3 (15)

26.  One patient died of pneumonia.
 Two patients have experienced disease progression till
date.
Results Cont..

27. Conclusions
 Within the limitations of small retrospective study, we conclude that
2-weekly docetaxel along with ADT is well tolerated and results in
acceptable oncological outcomes in metastatic Castration Naïve
Prostate Cancer.
 Nine (45%) patients achieved serological CR which is comparable to
32% reported in CHAARTED trial and superior to 15-18% reported
with ADT alone.1
 Incidence of grade 3-5 adverse events was 15% with 2-weekly
docetaxel which compares favorably to 30% with 3-weekly
docetaxel.1

28. June 2017

29. LATITUDE Trial

35. Adding abiraterone acetate plus prednisolone
(AAP) or docetaxel for patients (pts) with high-risk
prostate cancer (PCa) starting long-term
androgen deprivation therapy (ADT): directly
randomised data from STAMPEDE
3
5
Matthew Sydes
Statistician, Reader in Clinical Trials
MRC Clinical Trials Unit at UCL
Institute of Clinical Trials and Methodology
UCL, London, UK
Co-authors
Malcolm D Mason, Melissa R Spears, Noel W Clarke, David P Dearnaley,
Alastair WS Ritchie, J Martin Russell, Clare Gilson, Rob Jones,
Johann S de Bono, Silke Gillessen, Robin Millman, Shaun Tolan, John
Wagstaff, Simon Chowdhury, Jason Lester, Denise Sheehan,
Joanna Gale, Mahesh KB Parmar and Nicholas D James and the
STAMPEDE Investigators
Trial registration: NCT00268476

36. Summary
Strong evidence favouring AAP
Toxicity profiles quite different and well known
Weak evidence favouring AAP
No good evidence of a difference
Favours
SOC+AAP
Favours
SOC+DocP
Hazard ratio
Metastatic
progression-free
survival
Progression-free
survival
Failure-free
survival
Symptomatic skeletal
events
Cause-specific
survival
Overall survival
Head-to-head data in 566 pts (Nov-2011 to Mar-2013)
 Proportionately different time spent in
each disease state

37. Conclusions
1940 – 2003
“Era of ADT”
2015-2017
“Era of
sequencing”
2004 – 2014
“Era of Discovery”

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