Details of data from Prostate cancer clinical trials

Investigated (inv)

Comparator (comp)

ABI+pred+ADT

PLB+PLB+ADT

597

602

Phase:

3

Randomisation:

Double blind

Primary tumour:

Prostate

Subtype (biomarker):

mHSPC

Stage:

Line of therapy:

L1

Primary

ABI+pred+ADT

PLB+PLB+ADT

HR

p

rPFS

33.0 mo

14.8 mo

0.47 (0.39-0.55)

<0.001

OS

NR

34.7 mo

0.62 (0.51-0.76)

<0.001

Secondaries

ABI+pred+ADT

PLB+PLB+ADT

HR

p

time to the next skeletal-related event

NR

0.70 (0.54–0.92)

0.009 time to PSA progression

33.2 mo

7.4 mo

0.30 (0.26–0.35)

<0.001

time to subsequent prostate cancer therapy

NR

21.6 mo

0.42 (0.35–0.50)

<0.001

time to pain progression

NR

16.6 mo

0.70 (0.58–0.83)

<0.001

(all grades, %)

ABI+pred+ADT

PLB+PLB+ADT

p

Hypertension (gr.3)

20

10 NA

Hypokalemia (gr.3)

10

1 NA

ALT increased (gr.3)

5

1 NA

Hyperglycemia

13

11 NA

AST increased

15

11 NA

Bone pain

12

15 NA

Any cardiac disorder

12

8 NA

Back pain

18

20 NA

Fatigue

13

14 NA

Anemia

9

14 NA

ANy AE leading to treatment discontinuation

12

10 NA

AE leading to death

5

4 NA

—

Inclusion
Exclusion

- Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology - Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan - At least 2 of the following high-risk prognostic factors: Gleason score of greater than or equal to (≥8); presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis on CT or MRI Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 scan - ECOG performance status grade of 0, 1 or 2 - Adequate hematologic, hepatic, and renal function - Agrees to protocol-defined use of effective contraception.

- Active infection or other medical condition that would make prednisone use contraindicated - Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day - Pathological finding consistent with small cell carcinoma of the prostate - Known brain metastasis - Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer (the following exception are permitted): up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or antagonists or orchiectomy with or without concurrent anti-androgens prior Cycle 1 Day 1; participants may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 28 days prior to Cycle 1 Day 1)

Characteristics

ABI+pred+ADT

PLB+PLB+ADT

Age

<65 yr

221 (37%)

233 (39%)

65-74 yr

253 (42%)

249 (41%)

>74 yr

123 (21%)

120 (20%)

Median (range) yr

68 (38-89)

67 (33-92)

Gleason score at initial diagnosis

<7

4 (0.7%)

1 (0.2%)

7 9 (2%)

15 (2%)

≥8

584 (98%)

586 (97%)

—

Baseline pain score (BPI-SF Item 3) - no(%)

0 - 1

284 (50%)

288 (50%)

2 - 3

123 (22%)

137 (24%)

≥4

163 (29%)

154 (27%)

—

Patients with high risk at screening - no(%)

Gleason ≥8 + ≥3 bone lesions

573 (96%)

569 (95%)

Gleason ≥8 + MDV

82 (14%)

87 (14%)

≥3 bone lesions + MVD

84 (14%)

85 (14%)

Gleason ≥8 + ≥3 bone lesions + MVD

71 (12%)

70 (12%)

Extent of disease - no(%)

Bone

580 (97%)

585 (98%)

Liver

32 (5%)

30 (5%)

Lungs

73 (12%)

72 (12%)

Node

283 (47%)

287 (48%)

Extent of disease - no(%)

Prostate mass

151 (25%)

154 (26%)

Viscera

18 (3%)

13 (2%)

Soft tissue

9 (2%)

15 (3%)

Patients with ≥3 bone metastases at screening

586/597 (98.2%)

585/602 (97.2%)

Patients with previous prostate cancer therapy - no(%)

Radiotherapy

19 (3%)

26 (4%)

Hormonal

501 (84%)

501 (83%)

GnRH agonists/antagonists

449 (75%)

450 (75%)

Orchiectomy

73 (12%)

71 (12%)

Patients with previous prostate cancer therapy - no(%)

First-generation androgen receptor agonists

373 (62%)

371 (62%)

Other

7 (1%)

10 (2%)

—

Time from GnRH agonist/antagonist to first dose

Median (range) - mo

1.08 (0.1-3.0)

1.08 (0.1-3.5)

—

Ad-hoc:

no.pts inv.

no.pts comp.

ABI+pred+ADT

PLB+PLB+ADT

HR

p

OS (@3yr)

—

66%

49%

0.62

0.001 PSA response

—

91%

67%

1.36 <0.001

time to chemotherapy

—

NR

38.9 mo

0.44 (0.35–0.56)

<0.001

rPFS
OS

analisys of rPFS

ABI+pred+ADT

PLB+PLB+ADT

HR (95% CI)

Age

< 65 yr

30.7

14.6 0.44 (0.34-0.58)

≥ 65yr

34.5

18.2 0.49 (0.39-0.60)

ECOG

0

36.6

18.1 0.40 (0.32-0.50)

1 - 2

29.5

14.8 0.55 (0.44-0.70)

Visceral disease

Yes

30.7

18.3 0.53 (0.37-0.76)

No

34.5

14.8 0.45 (0.38-0.55)

Gleason score

< 8

NR

19.4 0.47 (0.15-1.46)

≥ 8

33

14.8 0.47 (0.40-0.55)

Bone lesions

≤ 10

NR

21.9 0.44 (0.32-0.59)

> 10

29.6

14.7 0.47 (0.38-0.57)

Above median PSA

Yes

30.7

18.1 0.52 (0.41-0.66)

No

33.1

14.8 0.43 (0.34-0.55)

Above median LDH

Yes

29.6

15.0 0.58 (0.46-0.73)

No

NR

14.9 0.36 (0.28-0.47)

Region

Asia

NR

22.1 0.32 (0.20-0.50)

East Europe

29.2

12.9 0.43 (0.33-0.56)

Region

West Europe

27.0

14.6 0.49 (0.36-0.68)

Rest of world

27.9

21.9 0.73 (0.49-1.08)

—

analisys of OS

ABI+pred+ADT

PLB+PLB+ADT

HR (95% CI)

Age

<65 yr

NR

33.7 0.62 (0.45-0.84)

≥65 yr

NR

35.1 0.64 (0.49-0.82)

ECOG

0 NR

38.2 0.64 (0.48-0.86)

1-2

NR

31.3 0.61 (0.46-0.79)

Visceral disease

Yes

NR

32.3 0.51 (0.33-0.79)

No

NR

35.1 0.66 (0.53-0.83)

Gleason score

<8

NR

0.62 (0.18-2.11)

≥8

NR

34.7 0.63 (0.51-0.77)

Bone lesions

≤10

NR

0.65 (0.45-0.96)

>10

NR

31.3 0.60 (0.47-0.75)

Above median PSA

Yes

NR

36.0 0.68 (0.51-0.89)

No

NR

33.9 0.58 (0.44-0.77)

Above median LDH

Yes

NR

33.9 0.68 (0.51-0.89)

No

NR

36.7 0.58 (0.44-0.77)

Region

Asia

NR

0.73 (0.42-1.27)

East Europe

NR

30.5 0.50 (0.36-0.69)

Region

West Europe

NR

38.1 0.75 (0.51-1.09)

Rest of world

NR

31.0 0.70 (0.45-1.09)

—

Prostate cancer: LATITUDE trial

EMA SPC links

2017-07-27

Karim Fizazi

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer

Investigated (inv)

Comparator (comp)

Randomisation:

Primary tumour:

Subtype (biomarker):

Stage:

Line of therapy:

Primary

ABI+pred+ADT

PLB+PLB+ADT

HR

p

rPFS

33.0 mo

14.8 mo

0.47 (0.39-0.55)

<0.001

OS

NR

34.7 mo

0.62 (0.51-0.76)

<0.001

Secondaries

ABI+pred+ADT

PLB+PLB+ADT

HR

p

time to the next skeletal-related event

NR

NR

0.70 (0.54–0.92)

0.009

time to PSA progression

33.2 mo

7.4 mo

0.30 (0.26–0.35)

<0.001

time to subsequent prostate cancer therapy

NR

21.6 mo

0.42 (0.35–0.50)

<0.001

time to pain progression

NR

16.6 mo

0.70 (0.58–0.83)

<0.001

(all grades, %)

ABI+pred+ADT

PLB+PLB+ADT

p

Hypertension (gr.3)

20

10

NA

Hypokalemia (gr.3)

10

1

NA

ALT increased (gr.3)

5

1

NA

Hyperglycemia

13

11

NA

AST increased

15

11

NA

Bone pain

12

15

NA