Prostate cancer: COU-AA-301 trial

Abbreviations

No EU-CTR

Investigated (inv)
Comparator (comp)

ABI+pred+ADT

PLB+pred+ADT

797

398

Phase:

3

Randomisation:

Double blind

Primary tumour:

Prostate

Subtype (biomarker):

mCRPC

Stage:

meta

Line of therapy:

L2

Primary
ABI+pred+ADT
PLB+pred+ADT
HR
p
OS
14.8 mo
10.9 mo
0.65 (0.54-0.77)
<0.001
Secondaries
ABI+pred+ADT
PLB+pred+ADT
HR
p
PSA response rate
29.1 %
5.5 %
<0.001
time to PSA progression
10.2 mo
6.6 mo
0.58 (0.46–0.73)
<0.001
rPFS
5.6 mo
3.6 mo
0.67 (0.58-0.78)
<0.001
ORR
14 %
2.8 %
-
<0.001
(all grades, %)
ABI+pred+ADT
PLB+pred+ADT
p
Fatigue
44
43
NA
Back pain
30
33
NA
Nausea
30
32
NA
Fluid retention/oedema
31
22
NA
Arthralgia
27
23
NA
Constipation
26
31
NA
Bone pain
25
28
NA
Hypokalemia
17
8
NA
Cardiac disorder
13
11
NA
Hypertension
10
8
NA
Hematuria
8
8
NA
Pyrexia
9
9
NA
Thrombocytopenia
4
3
NA
Neutropenia
1
<1
NA
  • Inclusion
  • Exclusion

- Metastatic Castration-Resistant Prostate Cancer Progression after one or two prior cytotoxic chemotherapies - At least one chemotherapy must have contained docetaxel - Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 - Medical or surgical castration with testosterone < 50 ng/dL - Adequate bone marrow, hepatic and renal function - Potassium ≥ 3.5 mmol/L - Able to swallow the study drug whole as a tablet - Informed Consent

- More than two prior cytotoxic chemotherapy regimens - Prior Ketoconazole for prostate cancer - Prior abiraterone acetate or other CYP17 inhibitor or investigational agents targeting the androgen receptor for prostate cancer - Uncontrolled hypertension - Active or symptomatic viral hepatitis or chronic liver disease - History of pituitary or adrenal dysfunction - Clinically significant heart disease - Other malignancy - Known brain metastasis - GI disorder affecting absorption - Not willing to use contraception

Characteristics
ABI+pred+ADT
PLB+pred+ADT
Age
Median (range)dc-comma yr
69 (42–95)
69 (39–90)
≥75 yrdc-comma no. of patients/total no (%)
220/797 (28)
111/397 (28)
Disease location - no. of patients/total no. (%)
Bone
709/797 (89%)
357/397 (90%)
Node
361/797 (45%)
164/397 (41%)
Liver
90/797 (11%)
30/397 (8%)
Lung
103 (13%)
45 (11%)
BPI-SF score for pain
No. of patients
792
394
Median score (range)
3.0 (0–10)
3.0 (0–10)
No. of previous cytotoxic chemotherapy regimens
1
558/797 (70%)
275/398 (69%)
2
239/797 (30%)
123/398 (31%)
ECOG PS
0 or 1
715/797 (90%)
353/398 (89%)
2
82/797 (10%)
45/398 (11%)
PSA
No. of patients
788
393
Median (range) — ng/ml
128.8 (0.4–9253.0)
137.7 (0.6–10114.0)
~
Gleason score at initial diagnosis
No. of patients
697
350
≤7
341 (48.9%)
161 (46.0%)
≥8
356 (51.1%)
189 (54.0%)
Extent of disease
Lungs
103 (13%)
45 (11%)
Prostate mass
60 (8%)
23 (6%)
Other viscera
46 (6%)
21 (5%)
Other tissue
40 (5%)
20 (5%)
Hemoglobin (g/dL)
No. of patients
779
389
Median
11.8
11.8
Range
7.3-16.1
7.2-16.5
LDH
N
783
386
Median
223.0
237.5
Range
84-3373
123-5125
Previous cancer therapy
Surgery
429 (54%)
193 (49%)
Radiotherapy
570 (72%)
285 (72%)
Hormonal
796 (100%)
396 (100%)
Other (incl. chemo.)
797 (100%)
398 (100%)
Ad-hoc:
no.pts inv.
no.pts comp.
ABI+pred+ADT
PLB+pred+ADT
HR
p
time to 25% of the patients having a skeletal event
9.9 mo
4.9 mo
rate of pain palliation in pts with a baseline pain score of >4
44%
27%
0.002
  • OS
analisys of OS
ABI+pred+ADT
PLB+pred+ADT
HR (95% CI)
Baseline ECOG
0 or 1
15.3
11.7
0.64 (0.56-0.79)
2
7.3
7.0
0.81 (0.53-1.24)
Baseline BPI level
<4
16.2
13
0.64 (0.50–0.82)
≥4
12.6
8.9
0.68 (0.53–0.85)
Disease progression according to
PSA concentration only
0
12.3
0.59 (0.42–0.82)
radiographic findings
14.2
10.4
0.69 (0.56–0.84)
Age
<65
14.4
11.2
0.66 (0.48–0.91)
≥65
14.8
10.7
0.67 (0.55–0.82)
Visceral disease at entry
Yes
12.6
8.4
0.70 (0.52–0.94)
No
15.4
11.2
0.62 (0.50–0.76)
Baseline PSA level above median
Yes
12.8
8.8
0.65 (0.52–0.81)
No
16.2
13.2
0.69 (0.53–0.90)
Baseline LDH level above median
Yes
10.4
8
0.71 (0.58–0.88)
No
0
16.4
0.64 (0.47–0.87)
No. of previous chemotherapy regimens
1
15.4
11.5
0.63 (0.51–0.78)
2
14.0
10.3
0.74 (0.55–0.99)
Baseline ALP level above median
Yes
11.6
8.1
0.60 (0.48–0.74)
No
-
16.4
0.73 (0.54–0.97)
Geographic region
North America
15.1
10.7
0.64 (0.51–0.80)
Other
14.8
11.5
0.69 (0.54–0.90)
analisys of
ABI+pred+ADT
PLB+pred+ADT
HR (95% CI)