VOLUME 28 䡠 NUMBER 9 䡠 MARCH 20 2010

JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T

Phase II Multicenter Study of Abiraterone Acetate Plus

Prednisone Therapy in Patients With Docetaxel-Treated
From the Department of Medicine, Joan
Castration-Resistant Prostate Cancer
and Sanford E. Weill College of Medicine
Daniel C. Danila, Michael J. Morris, Johann S. de Bono, Charles J. Ryan, Samuel R. Denmeade,
of Cornell University, Ithaca; Clinical
Matthew R. Smith, Mary-Ellen Taplin, Glenn J. Bubley, Thian Kheoh, Christopher Haqq, Arturo Molina,
Laboratories, Department of Radiology,
and Sidney Kimmel Center for Prostate
Aseem Anand, Michael Koscuiszka, Steve M. Larson, Lawrence H. Schwartz, Martin Fleisher,
and Urologic Cancers, Memorial Sloan- and Howard I. Scher
Kettering Cancer Center, New York, NY;
See accompanying editorial on page 1447 and articles on pages 1481 and 1489
Cancer Research United Kingdom Centre
for Cancer Therapeutics, Institute of
Cancer Research, Royal Marsden Hospi- A B S T R A C T
tal, London, United Kingdom; University
of California-San Francisco Comprehen- Purpose
sive Cancer Center, San Francisco; Persistence of ligand-mediated androgen receptor signaling has been documented in castration-
Department of Clinical Research and resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of
Development, Cougar Biotechnology, Los CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate
Angeles, CA; Chemical Therapeutics
tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce
Program, The Sidney Kimmel Compre-
hensive Cancer Center, The Johns
the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy.
Hopkins University School of Medicine,
Patients and Methods
Baltimore, MD; Division of Hematology-
Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with
Oncology, Massachusetts General Hospi-
tal; Dana-Farber Cancer Institute, Harvard
docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice
Medical School, and Beth Israel Deacon- daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome
ess Medical Center, Boston, MA. was ⱖ 50% prostate-specific antigen (PSA) decline, with objective response by Response
Submitted August 31, 2009; accepted
Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology
November 16, 2009; published online Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was
ahead of print at www.jco.org on also evaluated.
February 16, 2010.
Results
Supported by Cougar Biotechnology,
A ⱖ 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31
the Memorial Sloan-Kettering Cancer
Center Specialized Program of
ketoconazole-naïve and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses
Research Excellence (SPORE) Grant in were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS
Prostate Cancer (P50 CA92629), the was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200
Department of Defense Prostate days). CTC conversions with treatment from ⱖ 5 to ⬍ 5 were noted in 10 (34%) of 29 patients.
Cancer Research Program (PC051382) The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events
and the Prostate Cancer Foundation.
were seen.
Presented in part at the 45th Annual
Meeting of the American Society of Clini- Conclusion
cal Oncology (ASCO), May 29-June 2, AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated
2009, Orlando, FL, and the 44th Annual CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia)
Meeting of ASCO, May 30-June 3, 2008, was reduced by adding low-dose prednisone. The combination of AA plus prednisone is
Chicago, IL. recommended for phase III investigations.
Authors’ disclosures of potential con-
flicts of interest and author contribu- J Clin Oncol 28:1496-1501. © 2010 by American Society of Clinical Oncology
tions are found at the end of this
article.

Corresponding author: Howard I. Scher,

that are oncogenic for growth, of which AR over-
INTRODUCTION
MD, Genitourinary Oncology Service, expression is the most common.1 Tumor levels of
Department of Medicine, Sidney Kimmel Prostate cancer progression despite castrate levels ligand have received less attention. In 1984, Geller
Center for Prostate and Urologic Cancers,
Memorial Sloan-Kettering Cancer Center,
of testosterone is associated with a rising prostate- et al2 documented elevated levels of androgens in
1275 York Ave, New York, NY 10065; specific antigen (PSA) level and represents a tran- tissue homogenates of the prostates of men who
e-mail: Scherh@mskcc.org. sition to the lethal phenotype of the disease to were progressing on medical or surgical castra-
© 2010 by American Society of Clinical which most patients eventually succumb. The rise tion. Adrenal androgen synthesis was the postu-
Oncology in PSA, an indication that androgen receptor lated source, although a failure to completely
0732-183X/10/2809-1496/$20.00 (AR) signaling has been reactivated, is the result of suppress intratumoral androgens could not be
DOI: 10.1200/JCO.2009.25.9259 selective and/or adaptive changes in the AR itself excluded. The finding of increased intratumoral

1496 © 2010 by American Society of Clinical Oncology

 Phase II Study of Abiraterone Acetate in CRPC

androgens was subsequently confirmed in microdissected lo-

PATIENTS AND METHODS
cally recurrent and castration-resistant primary and metastatic
lesions.3-6 In 2004, Holzbeierlein et al7 first reported a microarray
Patients
analysis of newly diagnosed primary and metastatic and separately Castrate men (serum testosterone ⬍ 50 ng/dL [⬍ 2.0 nmol/L]) with
posthormone-treated primary and progressive castration-resistant metastatic prostate cancer who had experienced treatment failure with andro-
prostate cancers (CRPCs) that showed an up to five-fold induction gen deprivation therapy and docetaxel-based chemotherapy were eligible.
of several enzymes involved in steroid hormone production. The Disease progression was defined as documented PSA progression according to
finding, subsequently confirmed by others,8,9 suggested the pos- Prostate Specific Antigen Working Group 1 criteria25 and a PSA ⬎ 5 ng/mL, or
objective progression by Response Evaluation Criteria in Solid Tumors
sibility of intracrine signaling as an additional mechanism of
(RECIST) criteria26 for patients with measurable disease. Patients had to
AR reactivation. have received prior chemotherapy with docetaxel, and treatment with up
Abiraterone (CB7630, Cougar Biotechnology, Los Angeles, CA) to two prior chemotherapy regimens was permitted. Prior treatment with
is a novel, selective, irreversible, and potent inhibitor of 17-[alpha]- ketoconazole was allowed and was recorded separately. Eligibility criteria
hydroxylase/17,20-lyase (CYP17) enzymatic activity that has re- also included Eastern Cooperative Oncology Group (ECOG) performance
status (PS) of ⱕ 2, (Karnofsky PS ⱖ 50%), normal serum potassium, and
cently been demonstrated to further reduce testosterone levels in the
adequate hematologic, hepatic, and renal function. With the exception of
blood to undetectable range (⬍ 1 ng/dL),10,11 and is suggested to luteinizing hormone-releasing hormone agonists, a minimum of 4 weeks
reduce de novo intratumor androgen synthesis.12 Significant antitu- must have elapsed from discontinuation of prior prostate cancer therapies and
mor effects were seen in patients with progressive CRPC who had not a minimum of 6 weeks for antiandrogen therapy. Patients were excluded if
received prior chemotherapy, where secondary hormonal therapies they had brain metastases or spinal cord compression, active autoimmune
are traditionally used.11,13 Ketoconazole, a weak inhibitor of adrenal disease requiring corticosteroid therapy, uncontrolled hypertension, a de-
pressed cardiac ejection fraction or history of cardiac failure (New York Heart
steroid synthesis that suppresses many cytochrome P450 enzymes and Association class III or IV), or a serious concurrent medical illness. The trial
other enzymes involved in the conversion of cholesterol to preg- protocol was approved by the institutional review board at each site and
nenolone, has also shown activity in the same clinical context14,15 but was conducted in accordance with the Declaration of Helsinki, current US
is associated with significant toxicities.16-18
Recognizing that PSA levels also rise in patients who are
progressing after treatment with cytotoxic agents, we postulated Table 1. Patient Baseline Demographics and Clinical Characteristics
that these tumors might also be sensitive to a potent AR signaling No. of
inhibitor. In a separate trial, we showed significant antitumor Characteristic Patients %
effects of abiraterone acetate (AA) monotherapy in this patient Age, years
group, emphasizing further how considering these tumors as Median 69.5
Range 44-86
hormone-refractory can deny patients effective therapies.19 The
ECOG performance status
adverse events seen with AA monotherapy were largely those asso- 0 24 41
ciated with secondary hyperaldosteronism, including hypokale- 1 31 53
mia, fluid retention, and hypertension that required treatment 2 2 3
with the selective aldosterone inhibitor eplerenone or low-dose Unknown 1 2
Gleason score
steroids to suppress the hypothalamic-pituitary-adrenal axis,
Median 7
blunting the feedback rise in adrenocorticotropic hormone to re- Range 5-10
duce production of adrenal steroids with mineralocorticoid activ- Baseline PSA, ng/mL
ity.11,20 Anticipating phase III development, we designed this study Median 189.6
to confirm the antitumor activity of AA in patients with CRPC after Range 10.1-3,846
failure of docetaxel-based chemotherapy using the proposed reg- Involved metastatic sites
Visceral (with or without bone or soft tissue) 13 22
istration regimen of AA at 1,000 mg daily in combination with Bone only 11 19
prednisone at 5 mg twice daily, and separately, to begin to address Soft tissue only 8 14
the influence on outcome of the number and type of prior hor- Bone and soft tissue only 26 45
mone treatments, particularly ketoconazole.21 Importantly, the Prior hormonal therapies
evaluation of this steroid combination was further supported by LHRH agonists 57 98
Orchiectomy 3 5
our work indicating that low-dose steroids can reverse clinical AA
Antiandrogens 53 91
resistance and decrease steroid precursors upstream of CYP17 that Diethylstilbestrol 8 14
can activate AR signaling. Recognizing that PSA changes may not Steroids 21 36
be a reliable indicator of the antitumor effects of an AR signaling– Dexamethasone 5 9
directed therapy and that more informative indicators of clinical Other 20 34
Ketoconazole 27 47
benefit represent a critical unmet need for the management of
Prior lines of chemotherapy
CRPC, we also evaluated pre- and post-therapy circulating tumor 1 44 76
cell (CTC) number using an analytically valid assay that is cleared ⬎1 14 24
by the US Food and Drug Administration for use as an aid to Abbreviations: ECOG, Eastern Cooperative Oncology Group; PSA, prostate-
monitoring treatment and prognosis in patients with breast,22 specific antigen; LHRH, luteinizing hormone–releasing hormone.
colorectal,23 and prostate cancer.24

www.jco.org © 2010 by American Society of Clinical Oncology 1497

 Danila et al

Food and Drug Administration Good Clinical Practices, and local ethical ated separately using the CellTracks system (Veridex, Raritan, NJ), as
and legal requirements. described previously.27,28
Study Design Statistical Analysis
After written informed consent was obtained, eligible patients in this The primary end point of the trial was the proportion of patients who
multicenter phase II clinical trial received AA at 1,000 mg (four 250-mg tablets achieved a PSA decline of ⱖ 50% from baseline that was confirmed by a second
daily in the morning after an overnight fast) concurrently with prednisone at 5 value following treatment with AA plus prednisone. The combination would
mg twice daily. Treatment was administered in 28-day cycles, and up to 12 be considered worthy of further study if ⱖ 30% of patients met the end point
cycles of therapy were permitted; continuation beyond 12 cycles was allowed and not worthy of further study if fewer than 15% achieved the end point.
on approval by the investigators and sponsor. With a population of 50 patients, the null hypothesis would be rejected and
Patient Evaluation further study of the combination would be warranted if ⬎ 25% of eligible and
Patients were seen and examined at the beginning of every cycle while treated patients had a ⱖ 50% decline in PSA (alpha of 6% with 86% power).
receiving treatment, and adverse events were recorded using the National
Cancer Institute Common Toxicity Criteria, version 3.0. Potential attributions
to AA and prednisone were recorded separately. A CBC, chemistry panel, PSA, RESULTS
and androgen levels were evaluated monthly.
Antitumor Outcomes Patients
The primary study objective was determination of the proportion of Between June 2007 and November 2007, 58 men with CRPC
patients achieving a decline in PSA ⱖ 50% according to Prostate Specific were enrolled across seven study centers: six in the United States and
Antigen Working Group 1 criteria (PSA response). The maximal and 12-week one in the United Kingdom. Patient demographics and baseline char-
post-therapy declines in PSA were recorded using waterfall plots. The maximal
acteristics are listed in Table 1. All were heavily pretreated with a
decline had to be confirmed by a second value obtained ⱖ 4 weeks later.25
Patients who had metastatic disease evident on baseline imaging (computed number of hormonal therapies that included a median of four (range,
tomography scan, magnetic resonance imaging, or bone scan) had follow-up one to eight) prior antiandrogens in 52 (91%) and estrogens in nine
studies at 3-month intervals. Measurable disease response rate was reported (16%), while 27 (47%) had prior ketoconazole. While all had been
using the RECIST criteria, while post-treatment changes on radionuclide bone treated with prior docetaxel, 24% had also received a second chemo-
scan were reported as stable or progression per investigator’s assessment. therapy regimen. Consistent with the advanced state of the popula-
Time to PSA progression was calculated for patients with PSA decline tion, only 11 (19%) had disease limited to bone, while 13 (22%) had
ⱖ 50% from baseline at the time the PSA increased to 50% above the nadir and
was ⬎ 5 ng/mL. For those not meeting the PSA decline criteria, time to PSA
visceral spread, and 34 patients (59%) had soft tissue disease with or
progression was the time when PSA increased by 25% from baseline. without osseous spread. The median PSA level at baseline was 190
Other end points recorded were changes in ECOG PS, and pre-and ng/mL (range, 10 to 3,846 ng/mL). The median testosterone level was
post-therapy CTC counts (number of cells/7.5 mL of blood) were enumer- 4.8 ng/dL (range, below limit of detection [0.05] to 30.5 ng/dL).

A
Maximum PSA Change %

100

50

-50

-100
Fig 1. Changes in prostate-specific anti-
50% PSA decline, 8/27 (29.6%) 50% PSA decline, 7/31 (54.8%) gen (PSA) levels with abiraterone acetate
B plus prednisone. Waterfall plots of (A)
Week 12 PSA Change %

maximum PSA change and (B) change at

100 week 12. Patients with prior ketoconazole
exposure appear on the left side of the
50 panel in blue and those without prior ke-
toconazole exposure appear on the right
0 side of the panel in gold.

-50

-100

50% PSA decline, 7/27 (25.9%) 50% PSA decline, 14/31 (45.1%)

Prior ketoconazole exposure (n = 27) Reference Lines: -90%

No prior ketoconazole exposure (n = 31) -50%
PSA value clipped -30%

1498 © 2010 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

 Phase II Study of Abiraterone Acetate in CRPC

Soft tissue. Twenty-two of 28 patients with baseline scans had

Table 2. ECOG Performance Score Change From Baseline (N ⫽ 58)
target lesions assessed by computed tomography imaging; of these 22
Postbaseline ECOG Performance Score patients, partial responses were seen in four (18%), stable disease
0 1 2 lasting more than 3 months in 13 (59%), and disease progression in
Baseline ECOG
Performance No. of No. of No. of No. of five (23%).
Score Patients Patients % Patients % Patients % Osseous disease. Bone scans provided objective radiologic re-
0 24 22 2 — sponse information for 27 evaluable patients of the 34 patients with
1 31 14 15 2 baseline scans. By investigator assessment, 16 (59%) patients had
2 2 1 1 — stable disease and 11 (41%) patients experienced disease progression.
Totalⴱ 37 64 18 31 2 3
Clinical benefit and PS. Changes in ECOG PS from baseline were
Abbreviation: ECOG, Eastern Cooperative Oncology Group.
ⴱ
evaluated as an indication of clinical benefit (Table 2). Overall, 16
One patient did not have baseline ECOG recorded.
patients (28%) had an improvement in ECOG PS, with 14 patients
improving from PS 1 to PS 0, and one patient each improving from PS
2 to PS 1 or PS 0. Four patients (7%) had a worsening PS, with two
patients each changing from baseline PS 0 to PS 1 or PS 1 to PS 2. PS
Antitumor Effects remained stable among the remaining 37 (64%) patients.
PSA. A waterfall plot of the maximal PSA decline and 12-week Time to progression. The overall median time to PSA progres-
post-therapy PSA changes is shown in Figure 1. Overall, the propor- sion was 169 days (95% CI, 86 to 200 days); based on prior exposure to
tion of patients achieving a 50% or greater maximal decline in PSA was ketoconazole, the median time to PSA progression was 198 days (95%
43% (25 of 58; 95% CI, 30% to 55%), including 30% (8 of 27; 95% CI, CI, 82 to 393 days) among ketoconazole-naïve patients and 99 days
13% to 47%) of those who had received previous ketoconazole and (95% CI, 57 to 169 days) among ketoconazole-treated patients (Fig 2).
55% (17 of 31; 95% CI, 37% to 73%) of those who were ketoconazole- CTCs. Cell counts were available for all 38 patients treated at the
naïve. At the 12-week assessment, the overall proportion of patients Memorial Sloan-Kettering Cancer Center and four patients treated at
achieving a ⱖ 50% decline in PSA was 36% (21 of 58; 95% CI, 24% to the Royal Marsden Hospital. Overall, 29 (69%) patients had unfavor-
48%), including 26% (7 of 27; 95% CI, 9% to 435%) of those who had able baseline counts (ⱖ 5 cells/7.5 mL blood), of which 10 (34%)
received previous ketoconazole and 45% (14 of 31; 95% CI, 27% to converted to a favorable count after treatment (Table 3).
63%) of those who were ketoconazole-naive. The differences in the
proportion showing declines in PSA were not statistically significant. Safety and Tolerability
Overall, confirmed PSA responses of ⱖ 30%, ⱖ 50%, and ⱖ 90% The combination of AA and prednisone was well tolerated in this
decline were observed in 47%, 36%, and 16% of patients, respectively. heavily pretreated population. Grade 3 or 4 adverse events occurred
In the prior ketoconazole versus ketoconazole-naïve patients, the con- infrequently (Table 4). No significant hypertension or hypokalemia
firmed PSA decline of ⱖ 30%, ⱖ 50%, and ⱖ 90% were, respectively, were noted as clinical signs of mineralocorticoid excess with the pro-
nine (33%) versus 18 (58%), seven (26%) versus 14 (45%), and zero spective addition of prednisone. No patients required treatment with
(0%) versus nine (29%) patients. the mineralocorticoid antagonist eplerenone on this trial. Spinal cord

1.00 Keto: median, 99 days (95% CI, 57 to 169 days)

| No Keto: median, 198 days (95% CI, 82 to 393 days)
| Censored
||
|
0.75
| |
| |
| ||
Probability

|
Fig 2. Time to prostate-specific antigen
0.50 (PSA) progression with abiraterone acetate
| and prednisone in patients with and without
prior ketoconazole (Keto) exposure.
| |

0.25 | |
|

0 40 80 120 160 200 240 280 320 360 400 440 480 520 560

Study Day

www.jco.org © 2010 by American Society of Clinical Oncology 1499

 Danila et al

alocorticoid antagonist (eplerenone) or low-dose glucocorticoids.

Table 3. Patients With High CTC Counts at Baseline Stayed on Treatment
for a Shorter Time, Unless Counts Dropped With Treatment
These data, coupled with the high frequency of comorbid conditions
in this group and the risk of adrenal insufficiency in patients receiving
Time on Protocol (weeks)
glucocorticoids with prior docetaxel treatments, provided strong sup-
CTC/7.5 mL of Blood ⱕ 12 12-24 ⬎ 24 port for the combination of AA plus prednisone as the preferred
Baseline ⬍ 5 CTC (n ⫽ 13) regimen for further development.
Post-treatment CTC ⱖ 5 (n ⫽ 4) 1 1 2 This trial is, to the best of our knowledge, the first to address the
Post-treatment CTC ⬍ 5 (n ⫽ 9) 1 4 4
effect of prior ketoconazole exposure on outcome, although the time
Baseline ⱖ 5 CTC (n ⫽ 29)
Post-treatment CTC ⱖ 5 (n ⫽ 19) 9 7 3
interval between prior ketoconazole therapy and protocol entry was
Post-treatment CTC ⬍ 5 (n ⫽ 10) 1 3 6 highly variable, given that all of the patients were treated with chem-
otherapy in this interval. Patients with prior exposure to treatment
Abbreviation: CTC, circulating tumor cell.
and possible therapy-related selection pressure with ketoconazole had
an inferior percentage of PSA decline by ⱖ 50% compared with
patients without prior ketoconazole exposure. The time to PSA pro-
compressions were seen in two (3%) patients, which were deemed
gression tended to be shorter in patients with prior ketoconazole
related to disease progression.
exposure compared with ketoconazole-naïve patients. Although this
difference did not reach statistical significance, these findings were
DISCUSSION considered in the design of the exclusion criteria for this phase III trial
of AA and prednisone in patients with castrate metastatic prostate
This study is the second trial showing the activity of AA in patients
cancer postdocetaxel treatment failure. Unfortunately, the response to
with castration-resistant prostate cancer who have progressed on
prior treatment with ketoconazole was not known, so the question of
chemotherapy, and the first to explore the registration regimen
cross-resistance could not be fully addressed. These important find-
currently under evaluation in two prospective randomized, phase
ings will be addressed in the future in a dedicated trial.13
III, placebo-controlled registration trials with primary end points
Given the modest association with changes in PSA and the limi-
of survival and progression-free survival (www.clinicaltrials.gov,
tations of imaging distant metastases, there is an unmet medical need
NCT00638690, and NCT00887198).29,30 Antitumor activity was
to develop tumor-specific markers to aid the selection of targeted
demonstrated on the basis of post-therapy PSA declines, changes in
therapies and to assess clinical outcome. Using a US Food and Drug
soft tissue disease by RECIST, the lack of progression in bone, and
Administration-cleared, analytically valid assay for CTC enumeration
unfavorable to favorable changes in CTCs assessed with an analyt-
run in a Clinical Laboratory Improvement Amendments– certified
ically valid assay cleared by the US Food and Drug Administration
laboratory, we have shown that CTC counts are prognostic pretherapy
for monitoring treatment effects in CRPC. The results show that the
and the change in CTC number post-therapy is predictive of survival.31-33
decision to treat a patient with progressive castration-resistant disease
The CTC conversion rate after treatment with AA was also asso-
with chemotherapy does not necessarily mean that the tumor is resis-
ciated with an extended time on treatment. The number of patients
tant to further hormone treatments.
treated in this study was too small to further explore associations with
Noteworthy in this trial was the lower incidence of hypokalemia,
clinical outcome.
hypertension, and fluid retention (5%, ⬍ 5%, and ⬍ 10%, respec-
In conclusion, this study showed biochemical, CTC, and radio-
tively) compared with 55%, 17%, and 15%, respectively, relative to
logic evidence to support the evaluation of this AA and prednisone
our separate study of AA without prednisone.19 The hyperaldoste-
schedule in patients with progressive CRPC in a randomized study in
ronism syndrome developed in the absence of concomitant use of
the postchemotherapy setting with the primary end point of overall
low-dose steroids frequently required treatment with either a miner-
survival. Importantly, the trial also includes an evaluation of CTC num-
ber as an efficacy response biomarker in the phase III trial of AA plus
prednisone versus placebo. Moreover, these data indicate that the discov-
Table 4. Incidence of Most Frequent (ⱖ 5%) Treatment-Related Adverse ery and development of drugs targeting steroid receptor signaling
Events (N ⫽ 58) remain critically important for improving outcomes of this disease.
Grade 1 Grade 2 Grade 3
Grade 4
Adverse Event No. % No. % No. % No.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS
Nausea 8 14 0 0 0 OF INTEREST
Vomiting 5 9 2 3 0 0
Diarrhea 5 9 0 0 0
Although all authors completed the disclosure declaration, the following
Constipation 3 5 0 0 0
author(s) indicated a financial or other interest that is relevant to the subject
Fatigue 9 16 9 16 1 2 0
matter under consideration in this article. Certain relationships marked
Edema peripheral 4 7 1 2 0 0
with a “U” are those for which no compensation was received; those
AST 3 5 3 5 0 0
relationships marked with a “C” were compensated. For a detailed
ALT 2 3 1 2 0 0
description of the disclosure categories, or for more information about
Hypokalemia 3 5 0 0 0
ASCO’s conflict of interest policy, please refer to the Author Disclosure
Dyspnea 2 3 4 7 0 0
Declaration and the Disclosures of Potential Conflicts of Interest section in
NOTE: Two patients experienced hypertension, one each of grade 1 and Information for Contributors.
grade 2. Employment or Leadership Position: Thian Kheoh, Cougar Biotechnology
(C); Christopher Haqq, Cougar Biotechnology (C); Arturo Molina, Ortho

1500 © 2010 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

 Phase II Study of Abiraterone Acetate in CRPC

Biotech/Cougar Biotechnology (C) Consultant or Advisory Role: Daniel Provision of study materials or patients: Daniel C. Danila, Michael J.
C. Danila, Cougar Biotechnology (U); Johann S. de Bono, Cougar Morris, Johann S. de Bono, Charles J. Ryan, Matthew R. Smith,
Biotechnology (U); Matthew R. Smith, Cougar Biotechnology (U); Steve M. Mary-Ellen Taplin, Glenn J. Bubley, Christopher Haqq, Howard I. Scher
Larson, Cougar Biotechnology (C); Howard I. Scher, Cougar Biotechnology Collection and assembly of data: Daniel C. Danila, Johann S. de Bono,
(C), Veridex (U) Stock Ownership: Thian Kheoh, Cougar Biotechnology Charles J. Ryan, Mary-Ellen Taplin, Thian Kheoh, Christopher Haqq,
Honoraria: None Research Funding: Mary-Ellen Taplin, Cougar Arturo Molina, Aseem Anand, Michael Koscuiszka, Howard I. Scher
Biotechnology; Howard I. Scher, Cougar Biotechnology, Veridex Expert Data analysis and interpretation: Daniel C. Danila, Michael J. Morris,
Testimony: None Other Remuneration: None Samuel R. Denmeade, Mary-Ellen Taplin, Glenn J. Bubley, Thian Kheoh,
Christopher Haqq, Arturo Molina, Aseem Anand, Michael Koscuiszka, Steve
M. Larson, Lawrence H. Schwartz, Martin Fleisher, Howard I. Scher
Manuscript writing: Daniel C. Danila, Johann S. de Bono, Samuel R.
AUTHOR CONTRIBUTIONS
Denmeade, Mary-Ellen Taplin, Glenn J. Bubley, Thian Kheoh,
Christopher Haqq, Arturo Molina, Howard I. Scher
Conception and design: Daniel C. Danila, Johann S. de Bono, Final approval of manuscript: Daniel C. Danila, Michael J. Morris,
Christopher Haqq, Howard I. Scher Johann S. de Bono, Charles J. Ryan, Samuel R. Denmeade, Matthew R.
Financial support: Christopher Haqq, Arturo Molina Smith, Mary-Ellen Taplin, Glenn J. Bubley, Thian Kheoh, Christopher
Administrative support: Christopher Haqq, Arturo Molina, Haqq, Arturo Molina, Aseem Anand, Michael Koscuiszka, Steve M.
Howard I. Scher Larson, Lawrence H. Schwartz, Martin Fleisher, Howard I. Scher

12. Montgomery B, Mostaghel E, Nelson P, et al: 23. Cohen SJ, Punt CJ, Iannotti N, et al: Relation-
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