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PRESENTED AT 1 PRESENTED AT 1

Interim Analysis (IA) Results of COU-AA-302, a Randomized, Phase 3 Study of Abiraterone Acetate

(AA) in Chemotherapy-Naïve Patients (pts) With Metastatic Castration-Resistant

Prostate Cancer (mCRPC)

CJ Ryan,1 MR Smith,2 JS de Bono,3 A Molina,4 C Logothetis,5 P De Souza,6 K Fizazi,7 P Mainwaring,8 JR Piulats,9 S Ng,10 J Carles,11

PFA Mulders,12 T Kheoh4, T Griffin4, EJ Small,1 HI Scher,13 D Rathkopf,13 on behalf of the COU-AA-302 investigators

1Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA; 2Massachusetts General Hospital Cancer Center, Boston, MA;

3Royal Marsden Hospital, Sutton, UK; 4Janssen Research & Development, Los Angeles, CA; 5MD Anderson Cancer Center, Houston, TX; 6St. George Private

Hospital, Kogarah, Australia; 7Institut Gustave Roussy, University of Paris Sud, Villejuif, France; 8Haematology and Oncology Clinics of Australia, Brisbane, Australia;

9Institut Català d'Oncologia de l'Hospitalet, Barcelona, Spain; 10St. John of God Hospital, Subiaco, Australia; 11Hospital Universitari Vall d´Hebron, Barcelona, Spain;

12Radboud University Medical Centre, Nijmegen, Netherlands; 13Memorial Sloan-Kettering Cancer Center, New York, NY

x

Ryan et al, Proc ASCO 2012, LBA4518

PRESENTED AT 2 PRESENTED AT 2 PRESENTED AT 2 PRESENTED AT 2

Disclosures• Charles Ryan, Paul Mainwaring, Jose Piulats Rodriguez, Siobhan Ng, Joan Carles, Peter

Mulders, Eric Small, and Dana Rathkopf have no disclosures to report

• Matthew Smith has served as a paid consultant and received research funding from Cougar Biotechnology and Johnson & Johnson

• Johann de Bono has served as a paid consultant for Johnson & Johnson

• Arturo Molina, Thomas Griffin, and Thian Kheoh are employees of Janssen Research & Development, and own stock in Johnson & Johnson

• Christopher Logothetis has served as a consultant for Johnson & Johnson and Janssen Pharmaceuticals, Inc., and has received honoraria and research funding from Johnson & Johnson

• Paul De Souza has served as a paid consultant for Janssen Pharmaceuticals, Inc.

• Karim Fizazi has served as a paid consultant for Janssen Pharmaceuticals, Inc. and Cougar Biotechnology, and has received honoraria from Janssen Pharmaceuticals, Inc.

• Howard Scher has owned stock in Johnson & Johnson, has served as an abiraterone consultant/advisory board member, and has received consulting fees/grants/travel support fees from Cougar Biotechnology

This study was sponsored by Ortho Biotech Oncology Research & Development (unit of Cougar Biotechnology). Writing assistance was provided by I. Mills, PhD,

of PAREXEL, and was funded by Janssen Global Services, LLC.



Persistent Unmet Need in mCRPC

Current Therapies Have Limitations:

1. Restricted to Post-Chemotherapy Setting

2. OS Benefit in Chemo-Naïve Setting Without Objective Response or Impact on How a Patient Feels or Functions

3. Limited Penetrance of Chemotherapy

1. NCCN prostate cancer guidelines Version 3.2012. 2. Kantoff P, N Engl J Med. 2011; 363:411-422. Ryan et al, Proc ASCO 2012, LBA4518


Abiraterone Acetate:Androgen Biosynthesis Inhibitor

Pregnenolone

DHEA Androstenedione Testosterone DHT

17OH-Pregnenolone

Cortisol

Aldosterone

Androgens

Cholesterol

Abiraterone

Abiraterone



Abiraterone Acetate:

OS Benefit Shown in Post-Chemotherapy mCRPC Patients

Median Survival was 14.8 monthsImprovement of 3.9 months over Prednisone

control arm

1. de Bono J, N Engl J Med. 2011; 364:1995-2005.



Landmarks of Disease Progression in mCRPC

Baseline PSA

ProgressionTumor/Bone Progression

Pain

Death

Adapted from Halabi S. J Clin Oncol. 2009;27: 2766-2771.

Chemotherapy

ECOG PS Decline

Primary Endpoints: rPFS and OS

Secondary Endpoints

ECOG PS= Eastern Cooperative Oncology Group Performance Status.

24-48 months



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 dailyPrednisone 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 dailyPrednisone 5 mg BID

(Actual n = 542)

RANDOMIZED

1:1

• Progressive chemo-naïve mCRPC patients(Planned N = 1088)

• Asymptomatic or mildly symptomatic

Patients



COU-AA-302: rPFS Definition• Progressive disease (PD) by bone scan: Adapted from

Consensus Criteria1

– Blinded central radiologist review

– < 12 weeks after randomization

• ≥ 2 new bone lesions plus 2 additional at confirmation (“2+2”)

– ≥ 12 weeks after randomization

• ≥ 2 new bone lesions with subsequent confirmation

• PD (soft tissue lesions) by CT or MRI by modified RECIST criteria

• Death from any cause1. Scher H, J Clin Oncol. 2008;26:1148-1159.



COU-AA-302 Statistical Plan

IA = interim analysis. Ho, HR=1.0.

Overall Assumption rPFS OS

α 0.01 0.04

Power 91% 85%

HR 0.67 0.80

Expected events 378 773

IA3 (55% OS events)

425 Events = 0.0034

IA2 (40% OS Events)

311 Events = 0.0005

Planned OS Analysis

IA1 (~15% OS Events)

116 Events < 0.0001

1Q10 2Q10 3Q10 4Q10 1Q11 2Q11 3Q11 4Q11 1Q12 2Q12 3Q12 4Q12



Treatment Arms Evenly MatchedAA + P

(n = 546)Placebo + P

(n = 542)

Median age, years (range) 71 (44-95) 70 (44-90)

Median time from initial diagnosis to first dose (years) 5.5 5.1

Median PSA (ng/mL) 42.0 37.7

Median testosterone (ng/dL) 4.0 4.0

Median alkaline phosphatase (IU/L) 93.0 90.0

Median hemoglobin (g/dL) 13.0 13.1

Median lactate dehydrogenase (IU/L) 187.0 184.0

Gleason score (≥8) at initial diagnosis 53.9% 50.0%

Extent of disease

Bone Metastases >10 bone lesions

Soft tissue or node

83%

48%

49.1%

80%

47%

50%

Pain (BPI Short Form)

0-1

2-3

66%

32%

64%

33%


Youngren, Ken

Arturo added line for >+ 10 bone lesions; data not available in CSR; data will need to be added

PRESENTED AT 11 PRESENTED AT 11 PRESENTED AT PRESENTED AT 11

Treatment Duration and Discontinuation

AA + P(n = 542)

Placebo + P(n = 540)

Median duration of follow-up 22.3 mos.

Median no. of cycles of therapy, range 15 (1-33) 9 (1-31)

Treatment discontinued 69% 84%

Reasons for Discontinuation

Radiographic progression only 21% 30%

Unequivocal clinical progression* only 21% 25%

Radiographic and unequivocal clinical progression 11% 10%

Adverse event 7% 5%

Withdrew consent 6% 9%

Other 4% 5%

*Unequivocal clinical progression is one or more of the following: pain requiring opiates, chemotherapy, palliative radiation therapy, decline in ECOG PS, surgical intervention.

Data from safety population.Ryan et al, Proc ASCO 2012, LBA4518


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

ssio

n-F

ree

(%)

3 6 9 15 1812

546542

489400

340204

16490

123

00

AAPL

4630

Time to Progression or Death (Months)

AA + PPL + 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



rPFS Benefit Demonstrated Across Full Spectrum of Patient Subgroups

0.2 0.75 1 1.5

8.3

8.3

7.4

8.4

8.2

13.7

5.6

5.6

9.7

11.0

8.0

8.5

5.6

9.0

8.2

8.3

8.2

8.4

Variable Subgroup

Median (months)

AA Placebo HR 95% CI

FavorsAA

FavorsPlacebo

NE

13.7

NE

NE

11.1

NE

11.3

13.7

NE

NE

11.9

NE

NE

NE

11.5

NE

NE

11.5

ALL

0

1

0-1

2-3

YES

NO

< 65

≥ 65

≥ 75

YES

NO

YES

NO

YES

NO

N.A.

Other

All subjects

Baseline ECOG

Baseline BPI

Bone metastasis only at entry

Age

Baseline PSA above median

Baseline LDH above median

Baseline ALK-P above median

Region

0.43

0.45

0.35

0.42

0.51

0.48

0.38

0.36

0.45

0.57

0.44

0.40

0.37

0.48

0.50

0.34

0.36

0.52

(0.35-0.52)

(0.36-0.57)

(0.23-0.54)

(0.32-0.54)

(0.35-0.75)

(0.34-0.69)

(0.30-0.49)

(0.25-0.53)

(0.35-0.58)

0.39-0.83)

(0.33-0.58)

(0.29-0.54)

(0.28-0.49)

(0.36-0.65)

(0.38-0.66)

(0.25-0.47)

(0.27-0.48)

(0.39-0.69)


PRESENTED AT 14 PRESENTED AT 14 PRESENTED AT PRESENTED AT 14

Strong Trend in OS Primary End Point

Pre-specified significance level by O’Brien-Fleming Boundary = 0.0008.

546542

538534

482465

452437

2725

00

524509

503493

02

120106

258237

412387

100

80

60

40

20

0

0

Su

rviv

al (

%)

3 12 15 27

Time to Death (Months)

33

AA + PPL + P

6 9 30242118

AAPL

AA + P (median, mos): NR

PL + P (median, mos): 27.2

HR (95% CI): 0.75 (0.61-0.93)

P value: 0.0097

Data cutoff 12/20/2011.



Point Estimates for OS Favor AA in All Patient Subgroups

Variable Subgroup

Median (months)

AA Placebo HR 95% CI

FavorsAA

FavorsPlacebo

NE

NE

NE

NE

25.5

NE

NE

NE

NE

NE

26.9

NE

NE

NE

NE

NE

NE

NE

All subjects

Baseline ECOG

Baseline BPI

Bone metastasis only at entry

Age

Baseline PSA above median

Baseline LDH above median

Baseline ALK-P above median

Region

0.75

0.71

0.86

0.71

0.87

0.68

0.81

0.80

0.73

0.71

0.72

0.77

0.69

0.79

0.79

0.66

0.66

0.89

(0.60-0.93)

(0.55-0.92)

(0.58-1.28)

(0.54-0.94)

(0.59-1.29)

(0.48-0.96)

(0.61-1.06)

(0.51-1.24)

(0.57-0.94)

(0.51-1.00)

(0.55-0.94)

(0.54-1.09)

(0.53-0.91)

(0.55-1.12)

(0.60-1.04)

(0.46-0.94)

(0.49-0.88)

(0.65-1.22)

0.2 0.75 1 1.5

27.2

27.2

26.4

27.2

NE

27.2

27.5

NE

26.4

23.8

23.8

NE

23.6

27.5

23.6

27.5

27.2

NE

ALL

0

1

0-1

2-3

YES

NO

< 65

≥ 65

≥ 75

YES

NO

YES

NO

YES

NO

N.A.

Other



Subsequent Therapy Was Common

AA + P(n = 546)

n (%)


n (%)

No. with selected subsequent therapy for mCRPC 242 (44.3) 327 (60.3)

Docetaxel 207 (37.9) 287 (53.0)

Cabazitaxel 45 (8.2) 52 (9.6)

Ketoconazole 39 (7.1) 63 (11.6)

Sipuleucel-T 27 (4.9) 24 (4.4)

Abiraterone acetate* 26 (4.8) 54 (10.0)

*Prior to unblinding (e.g. not per protocol)Ryan et al, Proc ASCO 2012, LBA4518


Serologic and Clinical Responses

AA + P(n = 546)

Placebo + P(n = 542) RR (95% CI) P Value

PSA decline ≥50% 62% 24% NA <0.0001

N=220 N=218

RECIST: Defined objective response

Complete response

Partial response

Stable disease

Progressive disease

36%

11%

25%

61%

2%

16%

4%

12%

69%

15%

2.273 (1.591, 3.247)

<0.0001



Statistically Significant Improvement in All Secondary End Points

AA + P Placebo + P

Median (months)

Median (months) HR (95% CI) P Value

Time to opiate use (cancer related pain) NR 23.7 0.69 (0.57, 0.83) 0.0001

Time to chemotherapy initiation 25.2 16.8 0.58 (0.49, 0.69) <0.0001

Time to ECOG PS deterioration 12.3 10.9 0.82 (0.71, 0.94) 0.0053

Time to PSA progression 11.1 5.6 0.49 (0.42, 0.57) <0.0001

Data cut off 12/20/2011.

Patient Reported Outcomes favored AA +P vs Placebo +P Full data to be reported

Note: All secondary end points remain significant after adjusting for multiplicity testing



No New Safety Concerns Identified with Longer AA Treatment than in 301 Study

AA + P(n = 542)

%


%

All Grades Grades 3/4 All Grades Grades 3/4

Fatigue 39 2 34 2

Fluid retention 28 0.7 24 1.7

Hypokalemia 17 2 13 2

Hypertension 22 4 13 3

Cardiac disorders 19 6 16 3

Atrial fibrillation 4 1.3 5 0.9

ALT increased 12 5.4 5 0.8

AST increased 11 3.0 5 0.9

Most ALT and AST increases occurred during the first 3 months of treatmentRyan et al, Proc ASCO 2012, LBA4518


IDMC Unblinds Study at 2nd Interim Analysis

• February 2012

– Investigators and sponsors remained blinded

– Concluded that OS, rPFS, and secondary end points all favored AA

– Recommended unblinding study and that patients in placebo arm be offered treatment with AA



Time to All Landmarks Favored Abiraterone

Baseline PSA

ProgressionTumor/Bone Progression

Pain

Death

Adapted from Halabi S, J Clin Oncol 2009;27: 2766-2771.

Chemotherapy

ECOG PS Decline

Primary Endpoints: rPFS and OS

Secondary Endpoints

ECOG PS = Eastern Cooperative Oncology Group Performance Status.

24-48 months

p = 0.001p < 0.0001 p = 0.0053p < 0.0001

p < 0.0001 p = 0.0097



Summary

• In patients with asymptomatic and mildly symptomatic, chemotherapy-naïve mCRPC, treatment with abiraterone acetate plus prednisone:

– Delays disease progression

– Increases survival

– Extends time with minimal or no symptoms

– No new important safety signals



AustraliaA. BoyceA. Costello I. DavisP. de SouzaV. GanjuL. HorvathR. LynchP. Mainwaring G. MarxS. Ng F. ParnisJ. ShapiroN. Singhal M. Slancar G. Van HazelS. WongS. D. Yip

BelgiumP. Carpentier D. LuytenS. RotteyD. Schrijvers F. Van Aelst H. Van Poppel

CanadaT. Cheng J. ChinS. Ellard Y. FradetM. Gleave A. Joshua L. KlotzH. MartinsS. MukherjeeS. North S. Pautler F. Saad E. Winquist

FranceS. Abdel-Hamid M. Colombel K. FizaziB. Fléchon O. Haillot F. JolyS. Oudard F. Priou E. Raymond

GermanyP. AlbersM. Boegemann J. Gleissner J. Gschwend P. Hammerer A. Heidenreich M. KuczykK. MillerR. OetzelJ. Roigas T. Steuber M. Stöckle H. Suttmann M. Wirth

Greece E. EfstathiouC. Papandreou

ItalyS. Bracarda T. Marcello C. Sternberg

NetherlandsC. Bangma T. de Reijke W. Gerritsen P. Mulders

SpainJ. Arranz Arija J. Bellmunt J. Carles R. Lopez M. Lopez-Brea J. Piulats-Rodriguez

Sweden A. Bjartell J. Damber M. Haggman M. Hellstrom M. Seke

United KingdomJ. Brown S. Chowdhury J. de-Bono

T. ElliottS. Harland H. InnesN. James R. JonesD. MazharE. PaezA. Protheroe J. Staffurth

United States F. AhmannG. AndrioleE. Arrowsmith V. Assikis B. Baron W. BerryG. BubleyJ. CarneyL. ChuT. Cosgriff S. Denmeade H. Deshpande D. DucheneC. FerrariT. Flaig L. Fong

C. FormakerE. Frenkel N. GabrailJ. Garcia D. Georgel L. Gomella O. Goodman I. Gore J. Gullo J. Hainsworth O. Hamid A. HarzstarkT. Hutson D. King H. Koh A. Koletsky F. KudrikA. Lin P. Lara C. LogothetisR. LyonsJ. Maranchie M. ModianoJ. NievaL. Nordquist

J. PinskiA. Pantuck B. Polesz J. Polikoff D. Rathkopf D. QuinnC. Redfern S. RiggsC. RyanT. RodveltM. SalehB. SartorM. ScholzN. ShoreE. SmallM. SmithS. SrinivasM. Taplin U.Vaishampaya J. Vieweg M. Vira N. Vogelzang G. Wilding Y. WongE. Yu

AcknowledgmentsThe Patients, Their Caregivers and Families


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