changing landscape in the treatment of advanced prostate cancer

Changing Landscape in the Treatment of

Advanced Prostate Cancer

Dr Alok GuptaMD, DM,

Consultant Medical Oncologist

Max Super Speciality Hospital, Saket

Ex-Asst. Professor, AIIMS, New Delhi

Metastatic Prostate CancerChanging Landscape

• 1940 - 2003

• 2015-2016

• 2004 - 2014

Cancer Res. 1941;293-297

Arch Surg. 1941;209-223

75 YEARS LATER......

Androgen Deprivation therapy is still the standard of care in metastatic hormone

sensitive prostate cancer

Survival in Metastatic Prostate Cancer in Present Era

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.

• 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.

Docetaxel: TAX327 and SWOG 9916

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

Pro

bab

ilit

y o

f S

urv

ivin

g

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

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.

TROPIC – Cabazitaxel vs Mitoxantrone

• CRPC

• PD during or

after

docetaxel

RA

ND

OM

IZE

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.

TROPIC Primary Endpoint – OS

(ITT Analysis)

MP 377 300 188 67 11 1

CBZP 378 321 231 90 28 4

Numberat 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.

Pro

po

rtio

n o

f O

S (

%)

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

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

Tes

tost

eron

e (n

g/g

m)

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

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

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.

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



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)


AA Placebo

HR: 0.646 (95% CI: 0.54-0.77; P < .0001)

Su

rviv

al (%

)

100

80

60

40

20

00 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



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


*Most frequent cardiac disorders were tachycardia and atrial fibrillation.

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)

RANDOMIZED

1:1

• Progressive chemo-

naïve mCRPC

patients

(Planned N = 1088)

• Asymptomatic or

mildly symptomatic

Patients

Ryan et al. ASCO 2012

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

Pro

gre

ss

ion

-Fre

e (

%)

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

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

Su

rviv

al (%

)

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

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

pressureHormone Therapy

adaptation

RECURRENT TUMOR DEVELOPMENTCRPC

RESTORED AR ACTIVITY

(rising PSA)

>30% CRPC

AR

DEREGULATION

•amplification•overexpression

Penning & Knudsen

2010

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



Scher HI, et al. ASCO GU 2012. Abstract LBA1.

Patients with progressive

CRPC who failed docetaxel

chemotherapy

(N = 1199)


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




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

Su

rviv

al (%

)

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




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)


Docetaxel CRPC: Secondary Outcomes




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.


Docetaxel CRPC: Toxicity


Change Folio Title on Master /Arial 15pt /Unbold Whiteclinicaloptions.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


Change Folio Title on Master /Arial 15pt /Unbold Whiteclinicaloptions.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

Therapies With Survival Benefit for mCRPC

Agent IndicationRoute

Schedule

Cortico-

steroidsSymptoms

Contra-

indications

PSA

Response

Median OS

Benefit,

Mos

Sipuleucel-Tpre/post

docetaxel

IV every 2

wk x 3no

asymptomatic,

minimally sx

narcotics for

pain, liver

mets

no 4.1

Abiraterone pre/post

docetaxel

oral, empty

stomachyes* not specified

severe liver

dysfx, low K,

heart failure

yes

Post-doc:

4.6

Pre-doc: 4.4

Enzalutamide pre/post

docetaxeloral no not specified seizures yes

Post-doc:

4.8

Pre-doc: 4.0

Docetaxel mCRPCIV every 3

wkyes* not specified

moderate

liver dysfx,

cytopenias

yes 2.4

Cabazitaxelpost

docetaxel

IV every 3

wkyes* 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

metsNR 3.6

* In clinical trials and on FDA label.

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

2014

Survival in Metastatic Prostate Cancer in Present Era

ADT plus docetaxel greater tumor regression

AR independent clones

AR dependent clones

ADT + Docetaxel



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

Median Follow up : 50 m

ADT plus docetaxel: 58·9 m

ADT: 54·2 m

(HR1·01, 95% CI 0·75–1·36)

CHAARTED Trial

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)

Median follow up : 28.9 months

Survival in Metastatic Prostate Cancer

in Present Era

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


STAMPEDE: Docetaxel Significantly Improves Survival in Prostate Cancer

STAMPEDE: Study Design

Randomized, controlled, multiarm, multistage trial


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


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

Pro

babili

ty o

f O

S

Median OS (95% CI)

SOC 67 mos (60-91)

SOC + Doc 77 mos (70-NR)

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.


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.

Docetaxel in Hormone sensitive

prostate cancerStudy 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


cycles

790 0.61 (0.47-0.80)

[44.0 vs 57.6]

STAMPEDE 2005-

2013

• ADT


cycles + Pred 10mg daily


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.

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

STOpCaP: Meta-analysis of OS

Vale CL, et al. Lancet Oncol. 2016;17:243-256.

Summary

The value of docetaxel added to ADT for mHSPC is clearly established

– …but patient selection for appropriateness of chemotherapy is imperative.

Conclusions

• 1940 – 2003

• “Era of ADT”

• 2015-2016

• “Era of sequencing”

• 2004 – 2014

• “Era of Discovery”

Thank You

Dr Alok Gupta MD, DM,

Consultant Medical Oncologist

Max Super Speciality Hospital, Saket

Phone No. 9167164364

Email: [email protected]

changing landscape in the treatment of advanced prostate cancer

Health & Medicine