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Summary
Background Enzalutamide is an oral androgen-receptor inhibitor that has been shown to improve survival in
two placebo-controlled phase 3 trials, and is approved for patients with metastatic castration-resistant prostate cancer.
The objective of the TERRAIN study was to compare the ecacy and safety of enzalutamide with bicalutamide in
patients with metastatic castration-resistant prostate cancer.
Methods TERRAIN was a double-blind, randomised phase 2 study, that recruited asymptomatic or minimally
symptomatic men with prostate cancer progression on androgen-deprivation therapy (ADT) from academic,
community, and private health-care provision sites across North America and Europe. Eligible patients were randomly
assigned (1:1) via an interactive voice response system to receive enzalutamide 160 mg/day or bicalutamide 50 mg/day,
both taken orally, in addition to ADT, until disease progression. Patients were stratied by a permutated block method
(block size of four), by whether bilateral orchiectomy or receipt of luteinising hormone-releasing hormone agonist or
antagonist therapy started before or after the diagnosis of metastases, and by study site. Participants, investigators,
and those assessing outcomes were masked to group assignment. The primary endpoint was progression-free
survival, analysed in all randomised patients. Safety outcomes were analysed in all patients who received at least one
dose of study drug. The open-label period of the trial is in progress, wherein patients still on treatment at the end of
the double-blind treatment period were oered open-label enzalutamide at the discretion of the patient and study
investigator. This trial is registered with ClinicalTrials.gov, number NCT01288911.
Findings Between March 22, 2011, and July 11, 2013, 375 patients were randomly assigned, 184 to enzalutamide and
191 to bicalutamide. 126 (68%) and 168 (88%) patients, respectively, discontinued their assigned treatment before
study end, mainly due to progressive disease. Median follow-up time was 200 months (IQR 150256) in the
enzalutamide group and 167 months (102219) in the bicalutamide group. Patients in the enzalutamide group had
signicantly improved median progression-free survival (157 months [95% CI 115194]) compared with patients
in the bicalutamide group (58 months [4881]; hazard ratio 044 [95% CI 034057]; p<00001). Of the most
common adverse events, those occurring more frequently with enzalutamide than with bicalutamide were fatigue
(51 [28%] of 183 patients in the enzalutamide group vs 38 [20%] of 189 in the bicalutamide group), back pain (35 [19%]
vs 34 [18%]), and hot ush (27 [15%] vs 21 [11%]); those occurring more frequently with bicalutamide were nausea
(26 [14%] vs 33 [17%]), constipation (23 [13%] vs 25 [13%]), and arthralgia (18 [10%] vs 30 [16%]). The most common
grade 3 or worse adverse events in the enzalutamide or bicalutamide treatment groups, respectively, were hypertension
(13 [7%] vs eight [4%]), hydronephrosis (three [2%] vs seven [4%]), back pain (ve [3%] vs three [2%]), pathological
fracture (ve [3%] vs two [1%]), dyspnoea (four [2%] vs one [1%]), bone pain (one [1%] vs four [2%]), congestive cardiac
failure (four [2%] vs two [1%]), myocardial infarction (ve [3%] vs none), and anaemia (four [2%] vs none]). Serious
adverse events were reported by 57 (31%) of 183 patients and 44 (23%) of 189 patients in the enzalutamide and
bicalutamide groups, respectively. One of the nine deaths in the enzalutamide group was thought to be possibly
related to treatment (due to systemic inammatory response syndrome) compared with none of the three deaths in
the bicalutamide group.
Interpretation The data from the TERRAIN trial support the use of enzalutamide rather than bicalutamide in patients
with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer.
Funding Astellas Pharma, Inc and Medivation, Inc.
Introduction
Prostate cancer is predominantly driven by androgen
receptor signalling. The initial treatment of metastatic
prostate cancer is to reduce circulating testosterone
with luteinising hormone-releasing hormone (LHRH)
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Articles
Research in context
Evidence before the study
We reviewed the preclinical and clinical literature for evidence
suggesting that androgen receptor signalling continues to play
a part in the progression of castration-resistant prostate cancer,
even in patients who have disease progression while on
androgen-deprivation therapy including luteinising
hormone-releasing hormone analogues and antiandrogen
therapy. We searched PubMed between January, 2000, and
April, 2015, using the terms prostate cancer, metastatic, and
androgen receptor signalling. Articles published in languages
other than English were excluded. Preclinical data in models of
castration-resistant prostate cancer and phase 1 clinical data of
androgen signalling inhibitors in patients with metastatic
castration-resistant prostate cancer suggested that the disease
was still driven by the androgen receptor and that more potent
inhibitors of androgen signalling might benet patients with
castration-resistant prostate cancer. At the time the study was
initiated, no controlled clinical trial data assessing the benet of
more potent androgen receptor inhibition had been published;
however, phase 3 clinical trials were in progress. Data from both
the AFFIRM and PREVAIL trials of enzalutamide, published in
2012 and 2014, respectively, have subsequently shown that
enzalutamide has a signicant benet over placebo in terms of
overall survival and radiographic progression-free survival, as
well as objective tumour response in patients with measurable
soft tissue disease.
Added value of this study
TERRAIN is, to our knowledge, the rst randomised
head-to-head trial of enzalutamide versus bicalutamide in
death of about 30 months.2,3 Despite continued androgendeprivation therapy (ADT), disease progression most
often occurs because of further androgen receptor
signalling from both paracrine and autocrine sources of
androgenic ligands4 and, in most cases, the androgen
receptor is overexpressed.58
Bicalutamide, a non-steroidal oral antiandrogen, is
approved for use in conjunction with LHRH analogues in
men with hormone-treatment-naive prostate cancer, and
is often used in clinical practice. In the castration-resistant
setting, bicalutamide has been recommended as
second-line therapy by clinical guidelines, although this
recommendation is based on low levels of evidence.1,9,10
Controlled clinical trial data to support bicalutamide use
in patients with castration-resistant prostate cancer are
sparse, with little clinical benet shown when
bicalutamide was added to ongoing ADT.1113 Furthermore,
non-steroidal antiandrogens, such as bicalutamide, might
function as androgen receptor agonists in the setting
of androgen receptor overexpression or mutation, as
manifested by the antiandrogen withdrawal syndrome, a
reduction in serum PSA, and clinical improvement
observed upon antiandrogen discontinuation.14
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Articles
Methods
Study design and participants
TERRAIN was a multinational, randomised, double-blind,
phase 2 trial of enzalutamide versus bicalutamide in
patients with metastatic castration-resistant prostate
cancer recruited from academic, community, and private
health-care provision sites in North America and Europe
(appendix, p 1). Patients were eligible if they had
histologically conrmed adenocarcinoma of the prostate
with documented metastases, testosterone concentration
of 17 nmol/L (50 ng/dL) or lower, and disease
progression on ADT. Patients were regarded as having
metastatic disease at screening if they had at least one of
the following criteria: at least two bone lesions on bone
scans; soft tissue disease documented by CT or MRI; or
unequivocal pelvic lymphadenopathy with the short axis
greater than 20 cm in diameter, documented by CT or
MRI. We dened disease progression at study entry by
the presence of one or more of the following three criteria:
PSA progression (ie, three or more measurements of
rising PSA concentrations with an interval of at least
1 week between determinations); soft tissue disease
progression dened by Response Evaluation Criteria for
Solid Tumors (RECIST), version 11;21 or bone disease
progression dened by at least two new lesions on
bone scan. Eligible patients had asymptomatic or
mildly symptomatic prostate cancer (ie, Brief Pain
InventoryShort Form [BPI-SF], question 3, score <4),
were not using opiate analgesics for prostate
cancer-related pain, had an Eastern Cooperative Oncology
Group performance status of 01, and had a life
expectancy of at least 12 months. Key exclusion criteria
included previous progression on antiandrogen
therapy, previous chemotherapy, brain metastasis, and a
history of seizure. Patients were also excluded for
severe concurrent disease, active epidural disease, other
malignancy, clinically signicant cardiovascular disease,
and gastrointestinal disease aecting absorption.
Previous antiandrogen use was permitted, provided that
previous treatment was not administered within 6 weeks
before randomisation. We did not apply any age
restrictions for study inclusion. Full details of all
inclusion and exclusion criteria can be found in the
trial protocol.
The review boards of participating institutions approved
the study protocol, and the trial was done in accordance
with the Declaration of Helsinki. A data monitoring
committee was charged with reviewing the safety data
www.thelancet.com/oncology Vol 17 February 2016
184 excluded
165 met exclusion criteria or did not meet
inclusion criteria
8 withdrew consent
2 had pretreatment adverse events
9 other
0 lost to follow-up
126 discontinued intervention
75 progressive disease
14 adverse event
10 withdrawal by patient
6 protocol violation
6 death
15 other*
2 lost to follow-up
168 discontinued intervention
105 progressive disease
12 adverse event
20 withdrawal by patient
2 protocol violation
1 death
28 other*
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Articles
Enzalutamide (n=184)
Age, years
Bicalutamide (n=191)
71 (5096)
71 (4891)
54 (29%)
64 (34%)
172 (93%)
176 (92%)
8 (4%)
10 (5%)
Asian
3 (2%)
2 (1%)
1 (1%)
1 (1%)
Other
2 (1%)
>75 years
Race
White
Procedures
Ethnic origin
Not Hispanic or Latino
Hispanic or Latino
184 (100%)
187 (98%)
4 (2%)
Geographical region
Europe
North America
109 (59%)
112 (59%)
75 (41%)
79 (41%)
Weight, kg
8815 (5701841)
868 (5601435)
28 (1851)
28 (1844)
130 (71%)
146 (76%)
Grade 1
54 (29%)
45 (24%)
101 (55%)
117 (61%)
23
69 (38%)
67 (35%)
>3
10 (5%)
3 (2%)
4 (2%)
4 (2%)
Missing
Quality-of-life scores
Physical wellbeing
236 (41)
239 (44)
Functional wellbeing
200 (52)
203 (60)
Emotional wellbeing
183 (39)
188 (36)
Social wellbeing
222 (51)
224 (43)
324 (70)
330 (69)
PCSP
113 (41)
116 (42)
FAPSI
239 (52)
243 (51)
760 (141)
771 (153)
FACT-G
840 (133)
852 (134)
FACT-P
1168 (183)
1183 (188)
Disease localisation
Bone only
83 (45%)
92 (48%)
36 (20%)
29 (15%)
64 (35%)
69 (36%)
1 (1%)
1 (1%)
Yes
99 (54%)
98 (51%)
No
85 (46%)
93 (49%)
Missing
Previous antiandrogen use
87 (47%)
76 (40%)
After metastasis
97 (53%)
115 (60%)
Haemoglobin, g/L
Alkaline phosphatase, U/L
Lactate dehydrogenase, U/L
131 (86169)
132 (87169)
91 (341349)
95 (331163)
183 (891480)
185 (120506)
44 (3549)
21 (065000)
22 (014681)
Creatinine, mol/L
94 (65207)
86 (57187)
43 (3551)
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Outcomes
The primary endpoint was progression-free survival,
dened as the time from randomisation to the rst
progression event (ie, the earliest incidence of
centrally determined radiographic disease progression, a
skeletal-related event, or initiation of a new antineoplastic
therapy) or death from any cause, whichever occurred rst.
If the patient had more than one progression event on
the date of the rst progression event, the rst event
was selected from among those events according to
the following order: radiographic disease progression,
skeletal-related event, the initiation of a new antineoplastic
therapy, and death. Secondary endpoints included safety,
investigator-review-based progression-free survival (where
a progression event was dened as objective evidence
of radiographic disease progression based on the
assessments made by the investigators and not by
independent central review, a skeletal-related event,
initiation of new antineoplastic therapy, or death by any
cause, whichever occurred rst), time to PSA progression,
PSA response by week 13, and best PSA response.
We dened PSA progression as a 25% or greater increase
and an absolute increase of at least 2 g/L above the nadir
(or above the baseline value for patients with no decline in
PSA after baseline), which was conrmed by a second
consecutive PSA assessment at least 3 weeks later.
We dened PSA response as the percentage change in
PSA from baseline to the smallest PSA value after baseline,
on or before day 99 (ie, the upper boundary of the week 13
visit window). For patients with no decrease in PSA
between baseline and week 13, the PSA response by
week 13 was the smallest increase in PSA up to day 99. For
patients with no post-baseline PSA values up to day 99, we
set the PSA response by week 13 to missing. Exploratory
and other endpoints included assessments of Functional
Assessment of Cancer TherapyProstate (FACT-P) and
objective response. Denitions and associated analyses for
all endpoints are detailed in the appendix (p 5).
Enzalutamide (n=184)
The data analysis cuto date was Oct 19, 2014. Analysis
of the primary endpoint was a between-group
comparison of progression-free survival in the full
analysis set (all randomly assigned patients), with the
null hypothesis that progression-free survival would be
the same for patients in the enzalutamide group and
those in the bicalutamide group (ie, a hazard ratio [HR]
equal to 1).
We planned to do the nal analysis when a minimum
of 220 progression-free survival events were reported,
which would provide at least 85% power to detect an HR
of 067 for disease progression or death based on a
two-sided log-rank test, an overall signicance level of
005, and an expected median progression-free survival
of 6 months for the bicalutamide group. We aimed for a
study duration of 2 years (18 months of enrolment and
6 additional months of follow-up) to observe the required
www.thelancet.com/oncology Vol 17 February 2016
29 (04228)
33 (03230)
71 (39%)
73 (38%)
102 (55%)
110 (58%)
11 (6%)
8 (4%)
M0
67 (36%)
64 (34%)
M1
64 (35%)
74 (39%)
MX or unknown
53 (29%)
53 (28%)
Missing
Distant metastasis at initial diagnosis
382 (108243)
411 (177901)
1 (1%)
15
69 (38%)
76 (40%)
37 (19%)
610
29 (16%)
1115
10 (5%)
11 (6%)
>15
12 (7%)
12 (6%)
26 (14%)
22 (12%)
1 (1%)
2 (1%)
No
105 (57%)
109 (57%)
Yes
79 (43%)
82 (43%)
Missing
Previous radiation therapy
53 (29%)
63 (33%)
22 (12%)
17 (9%)
3 (2%)
1 (1%)
1 (1%)
1 (1%)
53 (29%)
52 (27%)
Metastatic disease
21 (11%)
19 (10%)
9 (5%)
9 (5%)
47 (25%)
Other
Previous surgeries or procedures of interest
Prostatectomy
43 (23%)
Orchiectomy
13 (7%)
11 (6%)
TURP
18 (10%)
22 (12%)
Cryoablation
Statistical analysis
Bicalutamide (n=191)
6 (3%)
4 (2%)
10 (5%)
9 (5%)
HIFU
2 (1%)
Other
13 (7%)
10 (5%)
10 (5%)
17 (9%)
15 (8%)
9 (5%)
Myocardial infarction
9 (5%)
13 (7%)
4 (2%)
4 (2%)
Data are median (range), number (%), and mean (SD). ECOG=Eastern Cooperative Oncology Group. PCSP=prostate
cancer subscale pain-related score. FAPSI=Functional Assessment of Cancer Therapy Advanced Prostate Symptom
Index. FACT-G=Functional Assessment of Cancer TherapyGeneral. FACT-P=Functional Assessment of Cancer
TherapyProstate. LHRH=luteinising hormone-releasing hormone. TURP=transurethral resection of the prostate.
HIFU=high-intensity focused ultrasound. *Out of 180 patients in the enzalutamide group and 190 patients in the
bicalutamide group. Brief Pain Inventory-Short Form, question 3; higher scores indicate a higher degree of pain.
In patients with bone metastases (147 and 161 patients in the enzalutamide and bicalutamide groups, respectively).
Patients could have had more than one reason for radiation therapy, more than one surgery or procedure, or more
than one previous cardiac disorder. Includes acute myocardial infarction.
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Articles
Enzalutamide
Bicalutamide
100
90
80
HR 044 (95% CI 034057); p<00001
70
60
50
40
30
20
10
0
0
Number at risk
Enzalutamide 184
Bicalutamide 191
12
15
18
21
24
27
30
33
33
7
21
4
13
2
8
2
5
1
Time (months)
159
133
131
85
107
61
86
44
71
30
52
13
B
100
Enzalutamide
Bicalutamide
90
80
74%
70
60
54%
50
40
33%
30
28%
25%
20
11%
10
10%
14%
4%
2%
0
Total number
of events
Radiographic
disease
progression
Skeletal-related
event
New
antineoplastic
therapy
Deaths
Enzalutamide
Bicalutamide
100
90
80
HR 051 (95% CI 036074); p=00002
70
60
50
40
30
20
10
0
0
Number at risk
Enzalutamide 184
Bicalutamide 191
158
12
15
18
21
24
27
30
33
33
7
20
3
13
2
8
2
5
1
Time (months)
147
104
120
73
99
51
82
38
65
30
49
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Number
Enzalutamide Bicalutamide
Enzalutamide
Bicalutamide
HR (95% CI)
Age (years)
<65
45
47
165 (113NR)
54 (3686)
033 (019057)
6575
85
80
044 (030066)
>75
54
64
118 (82171)
51 (36105)
055 (035087)
75
79
045 (030067)
109
112
044 (031061)
130
146
043 (032059)
54
45
153 (82207)
53 (3374)
042 (025071)
Geographical region
North America
Europe
ECOG performance status at BL
71
73
045 (029068)
102
110
046 (032065)
Bone only
83
92
053 (036078)
36
29
256 (108NR)
56 (28111)
032 (016063)
64
69
149 (82180)
48 (3264)
038 (025059)
At or below median*
92
95
195 (145NR)
82 (62127)
041 (028060)
Above median*
91
96
111 (84165)
41 (3356)
045 (032065)
038 (026058)
047 (034067)
Disease locations at BL
PSA BL value
LHRHa or orchiectomy
Before metastasis
83
77
After metastasis
101
114
Yes
99
98
187 (138NR)
64 (44103)
035 (024052)
No
85
93
118 (96157)
56 (3881)
055 (038079)
184
191
All patients
044 (034057)
05
Favours enzalutamide
10
15
20
Favours bicalutamide
Results
From March 22, 2011, to July 11, 2013, 375 patients were
randomly assigned from 84 sites in eight countries in
North America and Europe (184 to enzalutamide and
191 to bicalutamide; gure 1; appendix p 1), and were
included in the full analysis set. 372 (99%) patients
received at least one dose of the study treatment
(183 [99%] of 184 in the enzalutamide group and
189 [99%] of 191 in the bicalutamide group) and were
included in the safety analyses. The reasons for
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Articles
Enzalutamide
Bicalutamide
100
Patients without PSA progression event (%)
90
80
70
60
50
40
30
20
10
0
0
Number at risk
Enzalutamide 184
Bicalutamide 191
12
15
18
21
24
27
30
33
26
3
15
2
9
2
6
2
3
1
Time (months)
154
103
109
50
89
26
74
16
58
9
39
6
B
Enzalutamide
Bicalutamide
100
80
Change in PSA from baseline (%)
60
40
20
0
20
40
60
80
100
Observation
Enzalutamide
Bicalutamide
100
90
80
70
60
50
40
30
20
10
0
0
Number at risk
Enzalutamide 184
Bicalutamide 191
160
12
15
18
21
24
2
14
1
7
0
5
0
2
Time (months)
40
107
13
59
7
37
5
23
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100
Enzalutamide
Bicalutamide
80
60 p=00039 p=01502 p=00102 p=00575 p=00676 p=00011 p=00055 p=00428 p=00264 p=00260
51
42
40
34
27
43
41
37
34
28
25
25
21
20
36
26
23
33
25
22
FACT-G
FACT-P
17
9
0
PWB
SWB
EWB
FWB
PCS
PCSP
FAPSI
TOI
QoL domain
Figure 5: Patients with FACT-P improvement at any time during the study
The FACT-P instrument consists of 27 core items for assessing patient function, and the subscales reported in this
gure are all derived from these items (appendix p 6). Data are the proportion of patients with FACT-P improvement
at any time during the study. Improvement was dened as equal to or greater than the minimum clinically important
dierence from baseline (3 points for FACT-P subscales PWB, FWB, EWB, SWB, and PCS; 9 points for TOI; 7 points for
FACT-G; and 10 points for FACT-P; appendix p 6). EWB=emotional wellbeing. FACT-G=Functional Assessment of
Cancer TherapyGeneral. FACT-P=Functional Assessment of Cancer TherapyProstate. FAPSI=Functional Assessment
of Cancer Therapy Advanced Prostate Symptom Index. FWB=functional wellbeing. PCS=prostate cancer subscale.
PCSP=PCS pain-related score. PWB=physical wellbeing. QoL=quality-of-life. SWB=social wellbeing. TOI=Trial
Outcome Index.
Treatment-related adverse
events
Enzalutamide
(n=183)
Bicalutamide
(n=189)
Enzalutamide
(n=183)
Bicalutamide
(n=189)
52 (28%)
44 (23%)
14 (8%)
10 (5%)
9 (5%)*
3 (2%)
57 (31%)
44 (23%)
12 (7%)
1 (1%)
6 (3%)
73 (40%)
72 (38%)
17 (9%)
15 (8%)
10 (5%)
4 (2%)
1 (1%)
0
0
Myocardial infarction||
5 (3%)
1 (1%)
4 (2%)
2 (1%)
Atrial brillation
2 (1%)
1 (1%)
2 (1%)
1 (1%)
1 (1%)
1 (1%)
Seizure
Data are number of patients with at least one event (% of all patients). *Due to anaemia (n=1), renal failure (n=1),
paraplegia/spinal cord compression (n=1), systemic inammatory response syndrome (n=1), aspiration pneumonia
(n=1), paraneoplastic syndrome (n=1), and fatal cardiac events (n=3). Due to aspiration pneumonia (n=1), gastric
cancer (n=1), and disease progression (n=1). Due to systemic inammatory response syndrome. Patients could have
more than one cardiac event (not mutually exclusive). One patient had mitral valve incompetence and one had
supraventricular tachycardia (neither of these events occurred in patients in the enzalutamide group), and two had
congestive heart failure. ||Includes acute myocardial infarction.
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Enzalutamide (n=183)
Bicalutamide (n=189)
Grade 12
Grade 12
Grade 3
2 (1%)
Grade 3
Fatigue
49 (27%)
2 (1%)
36 (19%)
Back pain
30 (16%)
5 (3%)
31 (16%)
3 (2%)
Hot ush
27 (15%)
21 (11%)
Nausea
26 (14%)
33 (17%)
Hypertension
13 (7%)
Constipation
Diarrhoea
13 (7%)
6 (3%)
8 (4%)
21 (11%)
2 (1%)
24 (13%)
1 (1%)
21 (11%)
15 (8%)
2 (1%)
1 (1%)
Weight decrease
19 (10%)
1 (1%)
14 (7%)
Pain in extremity
18 (10%)
2 (1%)
9 (5%)
1 (1%)
Arthralgia
16 (9%)
2 (1%)
28 (15%)
2 (1%)
Data are number of patients with at least one event (% of all patients). Only adverse events that occurred in at least 10% of
patients in either group are presented. No grade 45 of the adverse events presented in this table were reported.
Discussion
In patients with metastatic castration-resistant prostate
cancer, enzalutamide signicantly improved progressionfree survival compared with bicalutamide. The superior
ecacy of enzalutamide over bicalutamide with respect
to progression-free survival was noted across all
prespecied subgroups, including age, geographical
location, baseline performance status, baseline PSA,
whether ADT was initiated before or after the diagnosis
of metastatic disease, and previous use of antiandrogens.
The denition of progression-free survival in this study
also included skeletal-related events or change of
antineoplastic therapy, and so it might be a more
clinically meaningful outcome than radiographic disease
progression and death alone.
Despite the widespread use of bicalutamide, evidence
of its clinical benets is scarce in the context of metastatic
castration-resistant prostate cancer. Data from the
TERRAIN trial show that enzalutamide is a more
eective treatment than bicalutamide for patients with
metastatic prostate cancer who progress on ADT, and are
consistent with the superior activity of enzalutamide
versus bicalutamide in preclinical models of metastatic
castration-resistant prostate cancer,15,18 thereby continuing
to show the importance of inhibiting androgen receptor
signalling in patients with castration-resistant prostate
cancer.58 The results of the TERRAIN trial conrm and
extend the results of enzalutamide activity in the phase 3
PREVAIL trial in chemotherapy-naive patients and in the
AFFIRM trial in patients who had received docetaxel.2,20
These data support the role of enzalutamide use in
patients with asymptomatic or minimally symptomatic
metastatic castration-resistant prostate cancer who had
disease progression while on ADT with an LHRH agonist
or antagonist, or after bilateral orchiectomy.
To our knowledge, the TERRAIN trial is the rst study
in men with metastatic castration-resistant prostate
cancer who had not had disease progression while on
previous antiandrogen treatment, with results that show
a consistent benet of enzalutamide over bicalutamide
on all prespecied, exploratory, and post-hoc endpoints.
Furthermore, results from the recently completed
STRIVE trial (NCT01664923), in which patients with
non-metastatic castration-resistant prostate cancer (M0)
were included in addition to patients with metastatic
cancer, suggest that patients assigned to enzalutamide
either early in their disease or after development of
metastatic disease derived more clinical benet than did
those assigned to bicalutamide.23
Enzalutamide had a favourable safety prole. Common
adverse events that occurred more frequently in the
enzalutamide group are consistent with the known safety
prole of enzalutamide reported in the phase 3 AFFIRM
and PREVAIL trials.2,20 Individual adverse events of
grade 3 or worse largely occurred at a similar frequency
(<1% dierence) between treatment groups, with the
exception of hypertension and back pain, which occurred
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