ASCO 12 Annual Meeting, June 1-5, 2012, Chicago, Illinois, USA
Androgen deprivation therapy (Intermittent therapy, Safety, Pharmacoeconomics, LHRH conjugated)
Castration resistance and high-risk disease among nonmetastatic (M0) prostate cancer (PC) patients
on androgen deprivation therapy (ADT).
Abstract No:1581
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 1581)
Author(s): Melissa Pirolli, Rohini Khorana Hernandez, Karynsa Cetin, Jane Quigley, Yanina Grant-Huerta,
Scott Stryker, Paul Smith, John Adams, Alexander Liede; SDI Health, Plymouth Meeting, PA; Center for
Observational Research, Amgen Inc, Thousand Oaks, CA; Amgen Inc., Thousand Oaks, CA; RAND
Corporation, Santa Monica, CA
Abstract:
Background: Prostate-specific antigen (PSA) is a well-known PC biomarker. In the M0 setting, rising PSAs
despite ADT is an indication of the development of castration-resistant prostate cancer (CRPC). In this
disease state, men are at risk for developing bone metastasis (BM), which is associated with significant
morbidity and may negatively affect survival. Using real-world data, we explored PSA-based criteria to
identify patients who develop CRPC while on ADT and the subsets that may be at increased risk of BM.
Methods: We used the Oncology Services Comprehensive Electronic Records (OSCER) database, which
includes electronic medical record (EMR) data on cancer patients from 328 urology and oncology clinics in
the US. Eligible patients were adult men with M0 PC with ≥1 PSA recorded between 3/1/2010 and 2/28/2011
and currently receiving ADT (gonadotropin-releasing hormone agonists or bilateral orchiectomy) for ≥6
months (mos). We defined CRPC as two sequential PSA rises while on ADT and high risk for BM as any
PSA ≥8 ng/mL or PSA doubling time (DT) ≤10 mos, as described by Smith MR et al, Lancet 2012. We
explored subsets of CRPC patients who may be at even higher risk of BM using PSA thresholds (≥8 ng/mL
and ≥20 ng/mL) and DT (≤4, 6, 8, and 10 mos). Results: Of 1,818 men with M0 PC receiving ADT ≥6 mos,
36% (N=646) met the CRPC definition, of whom 80% (N=517) had PSA ≥8 ng/mL and/or PSA DT ≤10 mos
(high risk). PSA DT alone explained 63% (44% / 70%) to 93% (65% / 70%) of subgroup eligibility (Table),
and emerged as a main driver in defining increased risk of BM for CRPC subsets. Conclusions: In this
analysis of EMR data, over one-third of men with M0 PC on ADT met criteria for CRPC, and most CRPC
patients (80%) may be considered at high risk for BM. Requiring ≥3 PSAs to define CRPC may be a
limitation; however, because PSAs are closely monitored in patients on ADT, these definitions of CRPC and
high risk may be useful in practice. These data suggest that PSA DT may be a more clinically meaningful
measure of defining CRPC subsets than absolute PSA thresholds.
CRPC subsets PSA ≥8 ng/mL PSA ≥20 ng/mL No PSA threshold (PSA < 8 ng/mL)
DT ≤10 mos
80%
70%
65%
DT ≤8 mos
78%
67%
60%
DT ≤6 mos
75%
63%
54%
DT ≤4 mos
70%
56%
44%
Neoadjuvant androgen pathway suppression prior to prostatectomy.
Abstract No:4520
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4520)
Author(s): Elahe A. Mostaghel, Peter Nelson, Paul H. Lange, Daniel W. Lin, Mary-Ellen Taplin, Steven P.
Balk, William J Ellis, Trevor Penning, Brett Marck, Lawrence D. True, Robert Vessella, Robert B.
Montgomery; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington, Seattle,
WA; Dana-Farber Cancer Institute, Boston, MA; Beth Israel Deaconess Medical Center, Boston, MA;
University of Pennsylvania, Philadelphia, PA; Department of Urology, University of Washington, Seattle, WA
Abstract:
Background: Optimizing tissue androgen suppression may provide better local and systemic control of
prostate cancer (PCa). Standard androgen deprivation therapy (ADT) has limited effect on tissue androgens
which remain in a range which supports tumor survival. We determined whether targeting androgen
metabolism using CYP17 and 5a-reductase (SRD5A) inhibitors would more effectively suppress tissue
androgens and tumor volume. Methods: Open label, multicenter neoadjuvant study in men with localized
PCa treated for 3 months prior to prostatectomy with zoladex and 1) avodart 3.5 mg QD; 2) avodart and
casodex 50 mg QD; or 3) casodex, avodart and ketoconazole 200 mg TID. Serum and tissue androgens
were measured by LC/MS/MS. Data were compared to men treated with standard ADT (LHRH agonist plus
Casodex), and untreated prostatectomy tissue. The primary outcome measure was suppression of tissue
dihydrotestosterone (DHT). Results: 35 men with intermediate/high risk PCa were enrolled. Tissue DHT was
suppressed 30 fold (> 95%) in all groups vs. LHRH agonist/Casodex (0.92 ± 0.20 pg/mg vs. 0.03± 0.03 for all
groups combined, p<0.0001). Tissue testosterone was 3-4 fold higher (consistent with SRD5A inhibition) in
all treatment groups vs. LHRH agonist/Casodex (0.33 vs. 0.07 pg/mg, p < 0.05). Differences in DHT/T
between groups 1 through 3 were not statistically significant. There was no correlation between tissue and
serum androgens, or tissue androgen and tumor volume (p> 0.05). In subset analysis, total serum DHEA
declined significantly in group 3, with free DHEA unchanged, suggesting differential effect on free and total
DHEA. Pathologic complete response (CR) was seen in 2 men, and an additional 8 men had <0.2 cc of
tumor, with the largest number of CR or near CR in the cohort treated with ADT, CYP17 and SRD5A
inhibitor, 4 of 12 men (33%). Due to small cohort size, differences were not statistically significant.
Conclusions: Addition of high dose SRD5A inhibition (with and without CYP17 inhibition) achieves prostate
DHT levels 30 fold below standard ADT. In this relatively high risk population, CR or near CR was seen in 10
of 35 men receiving protocol therapy. Further suppressing the androgen receptor signaling axis may provide
better local and systemic control of PCa.
Degarelix as neoadjuvant hormone therapy in patients with prostate cancer: Results from a phase
IIIb randomized, comparative trial versus goserelin plus bicalutamide.
Abstract No:e15199^
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15199^)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Malcom Mason, Christopher P Steidle, Charalambos Deliveliotis, Stephane Guerif, Xavier
Maldonado, Vincent Khoo, Thomas Wiegel, Egbert van der Meulen, Peter Bergqvist; Cardiff University
School of Medicine, Cardiff, United Kingdom; Northeast Indiana Research, LLC, Fort Wayne, IN; University
of Athens, Athens, Greece; CHU La Miletrie, Poitiers, France; Vall d'Hebron University Hospital, Barcelona,
Spain; The Royal Marsden, London, United Kingdom; University of Ulm, Ulm, Germany; Ferring
Pharmaceuticals, Copenhagen, Denmark
Abstract:
Background: The current approach in patients with high-risk localised or locally advanced PCa is ADT prior
to radiotherapy, which improves disease-specific and overall survival vs radiotherapy alone. Whether
degarelix, a GnRH antagonist performs comparably with the use of GnRH agonist under flare protection in
neoadjuvant settings has not yet been investigated. Methods: Patients with intermediate to high risk PCa
were randomised (3:1) to receive either degarelix or goserelin plus bicalutamide (G+B) for 12 wks. The
primary endpoint was the percentage reduction from baseline in prostate volume at wk 12 as measured by
TRUS. The non-inferiority margin was -10%. Other endpoints included changes in the IPSS, testosterone
and PSA. Results: 177 in the degarelix and 62 patients in the G+B arm have completed the trial. 62% and
38% of the patients had localised and locally advanced PCa, respectively. The primary endpoint was
successfully met establishing noninferiority between the two treatments in terms of prostate volume reduction
at wk 12 (Table). Conclusions: Degarelix was equally effective as prostate shrinking neoadjuvant hormone
therapy in patients with intermediate to high risk PCa, but elicited more pronounced LUTS relief compared
with G+B after 12 wks of treatment. Possible explanations may involve more pronounced effects on the
tumour per se or differences in the action of these drugs on peripheral GnRH receptors expressed in the
prostate and the urinary bladder.
G+B
Degarelix (240/80mg)
G=(3.6mg) Treatment difference (95% CI)
(n=180)
(n=64)
Mean (SD) % change in
-36.0 (14.5)
-35.3 (16.7)
-0.30 (-4.74, 4.14)
prostate volume (FAS, OC)
Mean (SD) change in IPSSa -1.71 (5.54)
0.11 (5.13)
-1.42 (-2.81, -0.035)b
Median (range) level of
0.05 (0.02-1.14)
0.05 (0.04-0.53) –
testosterone (ng/mL)
Degarelix (240/80mg)
(n=180)
G+B
G=(3.6mg)
(n=64)
Treatment difference (95% CI)
Median (range) level of
1.15 (0.05-27.9)
0.70 (0.1-4.3) –
PSA (ng/mL)
a Mean IPSS at baseline was relatively low; 9.0 for degarelix and 8.5 for G+B patients. In patients with a
baseline IPSS of 8-19, IPSS changes induced by degarelix but not by G+B were of clinical significance (2.99, n=72 vs -0.48 n=23; p=0.065). bp=0.045.
Final analysis of intergroup randomized phase III study of androgen deprivation therapy (ADT) plus
radiation therapy (RT) in locally advanced prostate cancer (CaP) (NCIC-CTG, SWOG, MRC-UK, INT:
T94-0110).
Abstract No:4509
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4509)
Author(s): Malcolm David Mason, Wendy Parulekar, Matthew Robert Sydes, Mahesh Parmar, John
Anderson, Jim Barber, Michael Donald Brundage, Richard Cowan, Mary K. Gospodarowicz, Charles Hayter,
John Hetherington, Andrea Clare Hiltz, Peter Kirkbride, Edward Kostashuk, Karen Sanders, Jinka Sathya,
Gregory P. Swanson, Bingshu E Chen, Padraig Richard Warde, NCIC-CTG PR3/MRC UK PR07
Investigators; Cardiff University, Cardiff, United Kingdom; NCIC Clinical Trials Group, Queen's University,
Kingston, ON, Canada; Medical Research Council Clinical Trials Unit, London, United Kingdom; MRC
Clinical Trials Unit, London, United Kingdom; The Royal Hallamshire Hospital, Sheffield, United Kingdom;
Velindre Hospital, Cardiff, United Kingdom; NCIC Clinical Trials Group, Queen's Division of Cancer Care and
Epidemiology, Kingston, ON, Canada; The Christie NHS Foundation Trust, Manchester, United Kingdom;
Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada; Credit Valley Hospital,
Mississauga, ON, Canada; Castle Hill Hospital, Hull, United Kingdom; NCIC Clinical Trials Group, Kingston,
ON, Canada; Weston Park Hospital, Sheffield, United Kingdom; British Columbia Cancer Agency, Surrey,
BC, Canada; CancerCare Manitoba, Winnipeg, MB, Canada; University of Texas Health Science Center at
San Antonio, San Antonio, TX; Department of Radiation Oncology, Princess Margaret Hospital and
University of Toronto, Toronto, ON, Canada
Abstract:
Background: Data from the SPCG-7 study and interim analysis of this trial have demonstrated an overall
survival (OS) benefit for RT when added to ADT. We present the protocol specified final analysis of
PR3/PR07. Methods: Patients with locally advanced (T3/T4, N0/NX, n=1057) or organ-confined prostate
cancer (T2,N0/NX, with either PSA > 40 μg/l or PSA > 20 μg/l and Gleason > 8, n=144) were randomized to
lifelong ADT (bilateral orchiectomy or LHRH agonist) or ADT + RT (65-69 Gy to prostate + seminal vesicles
with or without 45Gy to pelvic nodes). The primary outcome measure was OS; secondary outcomes included
disease-specific survival (DSS), time to disease progression and quality of life. Final analysis was planned
after 421 deaths. Results: 1,205 patients were randomized from 1995-2005, 602 to ADT alone and 603 to
ADT+RT (well balanced with respect to baseline characteristics). The median follow-up is 8.0 years and 465
patients have died (260 ADT, 205 ADT+RT). Adding RT to ADT significantly reduced the risk of death
(Hazard Ratio 0.70, 95% CI 0.57-0.85, p=0.001). 199 patients died of disease and/or treatment (134 on ADT
alone and 65 on ADT+RT). Competing risk analysis demonstrated that patients on the ADT alone arm had a
significantly higher chance of dying of disease related causes than those treated with ADT+RT (10 year
cumulative disease specific death rates 15% with ADT+ RT, 26% with ADT alone, p<0.0001). The addition of
RT to ADT had a small detrimental effect on late gastrointestinal toxicity and health-related quality-of-life (>
grade II proctitis, 0.3% ADT alone, 1.0% ADT+RT; mean change EORTC Rectal symptoms -0.3 ADT vs 1.7
ADT + RT, p=0.54). Conclusions: Mature data indicate a sustained and substantial overall survival and
disease specific survival benefit for ADT+RT in the management of patients with locally advanced prostate
cancer with minimal increase in late treatment toxicity. The benefits of combined modality treatment should
be discussed with all patients. Supported by NCI-US Grant CA077202, CCSRI Grants #14469 and #
015469, UK Medical Research Council Grant G9805643, UK National Cancer Research Network.
Progression of castrate-resistant (CR) disease in nonmetastatic (M0) prostate cancer (PC) patients: A
retrospective cohort study using data from the Henry Ford Health System (HFHS).
Abstract No:e15147
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15147)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Jennifer Beebe-Dimmer, Karynsa Cetin, Cecilia Yee, Lois Lamerato, Scott Stryker, Alexander
Liede, Kendra L. Schwartz, Vahakn B. Shahinian; Karmanos Cancer Institute Division of Population Studies
and Disparities Research, Wayne State University Department of Oncology, Detroit, MI; Center for
Observational Research, Amgen Inc, Thousand Oaks, CA; Karmanos Cancer Institute Division of Population
Studies and Disparities Research, Detroit, MI; Henry Ford Health System Department of Public Health
Sciences, Detroit, MI; Karmanos Cancer Institute Division of Population Studies and Disparities Research,
Wayne State University Department of Family Medicine and Public Health Sciences, Detroit, MI; University of
Michigan Medical School, Ann Arbor, MI
Abstract:
Background: Androgen deprivation therapy (ADT) is the cornerstone treatment of advanced PC, but is
frequently used in the M0 setting. After a variable period of hormone-sensitivity, most patients develop CR
disease (rising prostate-specific antigen [PSA] despite ongoing ADT). These men are at increased risk of
developing bone metastases (BMT), particularly in those with higher serum PSA and shorter PSA doubling
time (DT). The epidemiology and natural history of M0 CRPC has not been well-studied in a populationbased setting. Methods: A retrospective cohort study was conducted using HFHS administrative data and
included 691 men diagnosed with M0 PC between 1996 and 2005, who received ADT, with serial PSA
measurements to determine CR. Patient records through 12/31/2008 were reviewed for outcomes of interest.
CRPC was defined as 2 consecutive PSA rises, with “high risk” defined as PSA ≥8 ng/mL or PSA DT ≤10
months (mos) after the development of CRPC (Smith MR et al. Lancet 379:39-46, 2012). The risk of BMT
was estimated for the entire cohort and for the CRPC and high-risk CRPC subsets. Results: Of the 691
patients included in the cohort (median age: 73 years, 48% African American), 98% received only GnRH
agonists and 2% had orchiectomy. Median follow-up for the entire cohort after ADT initiation was 49 mos
(IQR=45). 101 patients (15%) met criteria for CRPC during follow-up, with a median of 18 mos on active ADT
prior to CRPC development (IQR=14). Of CRPC patients, 85% met criteria for high-risk (of those, 16% had
PSA ≥8 ng/mL, 12% had PSA DT ≤10 mos, and 72% had both). Among all patients, 12% (n=82) developed
BMT during follow-up, with 42% (n=36) of the high-risk CRPC subset developing BMT. Median time from
high-risk CRPC to BMT was 9 mos (IQR=17). Conclusions: The HFHS resource allowed for our
investigation of PSA characteristics corresponding to disease progression in a racially diverse patient
population. A substantial proportion of M0 PC patients on ADT will eventually develop CR disease. Once a
patient has CRPC, the risk of BMT is relatively high.
Increased cardiovascular risks associated with primary androgen deprivation therapy versus radical
prostatectomy among patients with localized prostate cancer.
Abstract No:e15130
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15130)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Jinan Liu, Lizheng Shi, A. Oliver Sartor, Richard Culbertson; Tulane University, New Orleans, LA;
Tulane Cancer Center, New Orleans, LA
Abstract:
Background: We examined whether primary androgen deprivation therapy (PADT), as compared to radical
prostatectomy (RP), was associated with cardiovascular disease and death. Methods: Male patients with
localized prostate cancer were identified in the SEER-Medicare (01/1998-12/2007). PADT patients were
matched to the RP patients via propensity score. Cardiovascular risks ((i.e., ischemic heart disease (IHD),
congestive heart failure (CHF), or cerebrovascular disease) were examined by Cox (PH) model;
cardiovascular death by Fine & Gray competing risk. Important independent variables were controlled for.
Results: The baseline variables were comparable. For the sample without cardiovascular disease (CVD)
history, significantly increased risks for IHD, CHF, and aggregate risk of CVD were found in PADT group (all
p-values <0.05), and the risks for cerebrovascular disease and cardiovascular death were also increased but
not significantly (both p-values>0.05); for the sample with CVD history, all the risks aforementioned were
significantly increased in PADT group (all p-values <0.05). Conclusions: In this retrospective study, PADT
was associated with increased cardiovascular disease and death when compared with RP, especially in the
sample with history of CVD.
PADT (n=670)
Median
follow-up
in
years
Without CVD history
IHD
2.32
CHF
2.64
Cerebrovascular
2.64
disease
Any of the above 2.20
Cardiovascular
2.87
death
RP (n=670)
Median
follow-up
%
n
in
years
n
201 30.0 2.51
111 16.6 2.71
155 23.1 1.435
55 8.2 2.137
1.160
1.541
1.774
2.964
0.001
<0.001
148 22.1 2.61
133 19.9 1.257
0.990
1.597
0.061
305 45.5 2.26
237 35.4 1.425
1.200
1.693
<0.001
14 2.09 2.95
6
0.916
6.591
0.074
PADT (n=715)
Median
follow-up
in
years
With CVD history
IHD
0.71
CHF
2.12
Cerebrovascular
1.93
disease
Any of the
0.42
above
Cardiovascular
2.79
death
Hazard Lower limit of Upper limit of
p value
95% CI
95% CI
% ratio
n
0.9 2.457
RP (n=715)
%
Median
follow-up
in
years
n
Hazard
% ratio
Lower limit
of
95% CI
Upper limit
of
95% CI
p
value
510 71.3 1.00
258 36.1 2.49
476 66.6 1.187
177 24.8 1.887
1.047
1.546
1.346
2.302
0.008
<0.001
321 44.9 2.23
299 41.8 1.338
1.138
1.573
<0.001
597 83.5 0.74
557 77.9 1.296
1.152
1.457
<0.001
46 6.43 3.04
15 2.1 3.124
1.700
5.739
<0.001
The relations between age and androgen deprivation therapy use among men receiving radiation
therapy for prostate cancer in the Medicare population.
Abstract No:e15150
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15150)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Jennifer L. Quon, James B. Yu, Pamela R. Soulos, Cary P. Gross; Yale University School of
Medicine, New Haven, CT
Abstract:
Background: For older men with prostate cancer who are undergoing radiotherapy, the benefit of
neoadjuvant and concurrent androgen deprivation therapy (ncADT) varies according to tumor characteristics
and life expectancy (LE). National Comprehensive Cancer Network (NCCN) guidelines recommend ncADT
for men with high-risk cancer characteristics, but not for men with low-risk cancer, or for men with LE < 5
years. Although older patients with shorter LE have the lowest likelihood of benefit, it is unclear whether
ncADT is used less frequently in this group. Methods: We used the Surveillance, Epidemiology, and End
Results-Medicare database to assess patterns of ncADT use among men diagnosed with prostate cancer
during 2004 through 2007 who received external beam radiation. Men were stratified according to NCCN
guidelines into low- (T1-T2a/N0/M0 and Gleason 2-6 and PSA< 10 ng/mL), intermediate- (T2b-T2c or
Gleason 7 or PSA 10-20 ng/mL), and high- (Gleason >7 or PSA> 20 ng/mL) risk groups. Men were further
stratified according to LE, which was calculated based on age and comorbid illness. We used logistic
regression to identify patient and clinical factors associated with ncADT use within each risk group. Results:
There were 11,080 men in the sample (mean age= 74.2 years; 83.5% white). The use of ncADT was highest
in the high-risk group (80.7%). However, a considerable number of men in the intermediate- (54.1%) and
low-risk (27.8%) groups also received ncADT. Compared to men with longer LE, men with LE < 5 years had
higher rates of ncADT use in all risk groups. For instance, in the low-risk group 32.7% men with LE < 5 years
received ncADT compared to 26.5% men with LE ≥ 10 years. Similarly, within each risk group, advancing
age was associated with a higher likelihood of receiving ncADT (OR for men aged 80-84 compared to 67-69
= 1.93(95% CI 1.37-2.70); 1.51(95% CI 1.22-1.87); and 1.71, (95% CI 1.14-2.57) for high-, intermediate-,
and low-risk groups, respectively). Conclusions: The use of ncADT in actual practice is not consistent with
guideline recommendations and is used more frequently among men who are older, have a shorter LE, and
are less likely to benefit from therapy.
Retrospective mathematical analysis of serial prostate specific antigen (PSA) measurements for
patients with M0 prostate cancer treated with intermittent androgen suppression (IAS).
Abstract No:e15201
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15201)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Celestia S. Higano, Yoshito Hirata, Koichiro Akakura, Nicholas Bruchovsky, Kazuyuki Aihara;
University of Washington, Seattle, WA; Institute of Industrial Science, The University of Tokyo, Tokyo, Japan;
Department of Urology, Tokyo Kosei Nenkin Hospital, Tokyo, Japan; Vancouver Prostate Centre,
Vancouver, BC, Canada
Abstract:
Background: Recently a phase III trial demonstrated that IAS was non-inferior to continuous AS in men with
M0 disease after primary or salvage radiation and quality of life was better in the intermittent arm (Crook
ASCO 2011). In that trial, men were treated with 8 months of AS followed by a variable time off AS driven by
the absolute PSA value. The Hirata mathematical model describes the dynamics of prostate cancer treated
with IAS (Hirata et al, J of Theoretical Biol 2010). In the model, there are three classes of cancer cells: a
class of androgen dependent (AD) cells and two classes of androgen independent (AI:X1 and AI:X2) cells.
During AS, AD cells will change to the two AI classes, and during the off treatment period, AI:X1 cells will
revert to AD cells whereas AI:X2 cells cannot revert to either AD or AI:X1 cells. Methods: After IRB
approval, we applied the Hirata model using serial monthly PSAs from men with M0 disease treated with IAS
from Japan, Canada, and the United States. The proportions of men from each country who fell into the 3
categories of patients previously defined by the Hirata model were compared. Results: Serial PSAs from 26
men from Japan, 72 from Canada, and 79 from US were put into the model. The 3 categories of patients
from the model include: (i) those with disease that will remain androgen sensitive and will respond to IAS
without development of castration resistance (CRPC) (ii) those who will benefit from IAS but will develop
CRPC sooner than those in group (i), (iii) those for whom continuous AS is superior to IAS. The datasets
from each country show a similar distribution among the categories, and overall there were 42%, 51%, and
7% falling into groups i, ii, and iii respectively. Conclusions: This retrospective analysis shows that men with
M0 disease treated with IAS fall into the 3 categories predicted by the Hirata model in similar proportions,
regardless of country of origin. The ability to apply this model to the individual patient in the clinic is currently
under development. The model may ultimately be able to optimize both the on and off treatment durations of
IAS and to predict those patients who will most benefit from this approach.
A matched case control study in veteran patients with high cardiovascular risk (CVR) examining
cardiac medication (CMed) prescribing differences between prostate cancer (PC) patients on
androgen deprivation therapy (ADT) and men without PC.
Abstract No:e15179
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15179)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Yash R. Patel, Angela D. Reed, Marietta L. Moore, Angela C. Canfield, James A Kruer, Noah M.
Hahn; St. Mary's Mercy Livonia Hospital, Livonia, MI; Indiana University Melvin and Bren Simon Cancer
Center, Indianapolis, IN; Indiana University Simon Cancer Center/Richard L. Roudebush VAMC,
Indianapolis, IN
Abstract:
Background: Conflicting reports exist on associations between ADT and CVR in PC patients (pts). The
current study tests the hypothesis that underutilization of CMeds in PC pts with known CVR contributes to
their increased cardiac event rates. Methods: Veteran men without malignancy (no-PC, controls) and men
with PC on ADT (cases) were consented through the IUSCC IRB-approved biorepository protocol. All pts
had high CVR defined as the presence of > 2 of the following: age > 45, Body mass index (BMI) > 30 kg/m 2,
hypertension (HTN), hyperlipidemia (HL), diabetes (DM), and smoking history (SmHx). Prior coronary artery
disease (CAD) qualified pts as severe CVR. Each case was matched with 2 controls in the following order of
priority: prior CAD, HTN, DM, HL, SmHx, age, BMI, and race. CMeds prescriptions included in the table
below were verified via VAMC pharmacy records. CMeds prescription differences between cases and
controls were tested by one-sided chi-Squared testing for each medication and by logistic regression for
different classes of medications. Results: Between 1/2007 and 6/2011, 53 cases and 254 controls were
enrolled in the IUSCC VAMC clinics. After 2:1 matching, the final cohort included 53 cases and 106 controls.
Demographics included: prior CAD – 27%, HTN – 60%, DM – 31%, HL – 40%, SmHx – 63%, BMI – median
29.7 kg/m2, Age – median 66 yrs. Controls were younger than cases (71.4 yrs cases – 63.1 yrs controls,
p<0.0001). No statistically significant differences in CMed prescribing frequency were observed between the
two groups. Conclusions: Differences in CMed prescribing practices between PC pts and no-PC men with
high CVR is not a factor contributing to increased cardiac events in PC pts on ADT in our Veteran
population. The study size warrants confirmation in a larger dataset.
PC
no-PC
Medication
P value
(n=53) (n=106)
N (%)
N (%)
Aspirin
10 (18.9) 32 (31.4) 0.10
Clopidogrel
3 (5.7) 6 (5.9) 0.96
ACEIs/ARBs
16 (30.2) 40 (39.2) 0.27
β-blockers
17 (32.1) 34 (33.3) 0.87
Insulin
6 (11.3) 10 (9.8) 0.77
Oral hypoglycemics 10 (18.9) 16 (15.7) 0.62
Statins
Risk of adverse cardiovascular events (CVE) and incident diabetes mellitus (DM) in patients (pts)
with prostate cancer (PC) treated with androgen deprivation therapy (ADT): A meta-analysis of
adjusted observational results.
Abstract No:e15192
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15192)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Lorenzo D'Ambrosio, Federica Brusa, Fabrizio D'Ascenzo, Erica Cavallero, Giuseppe BiondiZoccai, Paola Boccone, Paolo Bironzo, Glenn N Levin, Robert H Eckel, Richard V Milani, Arthur I.
Sagalowsky, Mauro Gasparini, Giovanni Grignani, Fiorenzo Gaita, Libero Ciuffreda, Massimo Aglietta;
Medical Oncology, Institute for Cancer Research and Treatment, Candiolo, Italy; Oncologia Medica 1, Centro
Oncologico ed Ematologico Subalpino, Turin, Italy; Division of Cardiology, University of Turin, Torino, Italy;
Division of Cardiology, University of Modena and Reggio Emilia, Modena, Italy; Oncologia Medica 1, Centro
Oncologico ed Ematologico Subalpino, Torino, Italy; Cardiac Care Unit, Baylor College of Medicine and
Michael E. DeBakey Medical Center, Houston, TX; University of Colorado, Aurora, CO; Division of
Cardiology, Ochsner Medical Center, New Orleans, LA; University of Texas Southwestern Medical Center,
Dallas, TX; Department of Mathematics, Politecnico di Torino, Torino, Italy; Division of Cardiology, University
of Turin, Corso Dogliotti, Italy; Division of Oncology, AOU S.Giovanni Battista - Molinette, Turin, Italy;
Medical Oncology, Institute for Cancer Research and Treatment, Candiolo, Italy
Abstract:
Background: ADT is a mainstay treatment in pts with PC and is supposedly associated to an unfavorable
metabolic and cardiovascular profile. Recently, a meta-analysis of randomized controlled trials (RCT) found
no association between ADT and increased risk of CVE (JAMA 2011). However, no conclusive data were
available about ADT association with metabolic changes and adverse CVE or DM because of pts selection in
RCT. Therefore, we performed a meta-analysis of adjusted observational results in order to look for DM and
CVE onset in an ADT unselected population. Methods: Medline, Cochrane Library and Biomed Central were
searched for articles addressing adverse events related to ADT in patients with PC. Selection criteria were:
not RCT, pts assigned to ADT or not, adjusted risk of CVE and DM according to ADT. Exclusion criteria
were: duplicate publication, comparison of two different strategies of ADT (different drugs or duration).
Cardiovascular death was the primary endpoint; non-fatal myocardial infarction (MI), stroke/transient
ischemic attack (TIA) and new DM onset were secondary endpoints. Random effects model with generic
inverse variance weighting was used to estimate adjusted risks as odds ratios (OR) with 99% confidence
interval (CI). Results: We selected 12/2100 screened studies. We included 208643 pts of which 102177
received ADT. At a follow up of 5 years (4-7.5), ADT did not result as an independent risk factor for
cardiovascular death (OR= 1.04; 99% CI= 0.94-1.14). No increased risk of MI (OR= 1.13; CI= 0.86-1.48) or
of stroke/TIA (OR= 1.11; CI= 0.78-1.57) were detected. Incident DM was more frequent among ADT pts
(OR= 1.32; CI= 1.14-1-53). Even in 7205 pts with previous CVE (2450 received ADT), ADT was not
associated with an increased risk of overall death (OR= 1.23; CI= 0.87-1.75). Meta-regression analysis
showed no significant interactions between duration of ADT and cardiovascular death or incident DM.
Conclusions: In non-selected pts,ADT appears to increase the risk of incident DM, but not of CVE or
stroke/TIA. Moreover, overall mortality is not increased in pts with a history of CVE.
Assessment of the variability of and effect of hormone therapy on circulating tumor cell numbers and
androgen receptor expression in patients with prostate cancer.
Abstract No:e15141
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15141)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Noel W Clarke, Sarah E Marley, Andrew M. Hughes, Anthony F Nash, Michael D Malone, Jim W
Growcott, Darren R Hodgson, Robert Sloane, David J Moore, Tim H Ward, P. Anthony Elliott, Caroline Dive;
Department of Urology, The Christie NHS Foundation Trust, Manchester, United Kingdom; AstraZeneca,
Macclesfield, United Kingdom; AstraZeneca Pharmaceuticals, Macclesfield, United Kingdom; Paterson
Institute for Cancer Research, The University of Manchester, Manchester, United Kingdom; Paterson
Institute for Cancer Research, Manchester, United Kingdom; The Christie NHS Foundation Trust,
Manchester, United Kingdom
Abstract:
Background: In prostate cancer (PC) CTC number and character may offer a means of assessing disease
load and target engagement. However, capture platforms differ, presenting challenges to enumeration and
molecular characterisation. We report the findings of a pilot study assessing the intra- and inter-patient
variability of 2 different platforms, and the feasibility of measuring CTC-androgen receptor (AR) expression
by immunohistochemistry (IHC) in a single platform. Methods: Following ethical approval, 4 PC cohorts (n =
12, 12, 10, and 6 respectively) were recruited; #1 localised, no hormonal therapy; #2 and #3: castrateresistant, receiving LHRHa or LHRHa and bicalutamide, respectively; #4: newly diagnosed locally advanced,
no hormonal therapy. Blood (2 x 10 mL, 2 visits #1-3; 2 x 10 mL,1 visit #4) was taken and CTCs isolated
using either the Cell Search CTC Test (Veridex) or Isolation by Size of Epithelial Cells Technique (ISET) for
enumeration, and ISET for AR expression (H-score [(% 1*1+) + (% 2*2+) + (% 3*3+)]). Results: There was
no correlation between Veridex and ISET for detection of CTCs (Veridex enumeration:14%, 63%, 53% and
0% of samples in #1 - 4, respectively, vs ISET enumeration: 100% of samples across all cohorts) with the
latter platform detecting a significantly higher number of CTCs/4mls from patients in cohort #4 vs #1 (GLS
Means 119 vs 46, p=0.0135). For both platforms there was no evidence of a systematic change in the counts
at two separate visits 2 weeks apart. AR was detectable in approximately 25-35% CTCs from all cohorts and
there were no significant differences in the H-score between the cohorts, although the number of AR-positive
cells/4mls was significantly higher in #4 vs #1, and #2 (GLS Means 25 vs 14, 15, p= 0.0197, 0.0398,
respectively). Conclusions: Populations of CTCs detected by Veridex and ISET appear stable over short
durations (2 weeks) and AR was detected in a proportion of CTCs by ISET using IHC. Further work is
required to find alternative methodologies with greater specificity.
Secondary chemoprevention using short period (3 months) of LHRHa as an option for men with lowrisk localized prostate cancer (LRPC) before active surveillance (AS).
Abstract No:e15105
Citation:
J Clin Oncol 30, 2012 (suppl; abstr e15105)
Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with
the 2012 Annual Meeting but not presented at the Meeting, can be found online only.
The publication-only abstracts are not included in the print or USB versions of the ASCO Annual
Meeting Proceedings Part I, but they are citable to the Journal of Clinical Oncology as a
supplement (see citation on left).
Author(s): Olivier Cussenot, Sarah Drouin, Christophe Egrot, Jean-Nicolas Cornu, Philippe Sebe, Pierre
Mozer, Pierre Conort, Christophe Vaessen, Francois Haab, Marc-Olivier Bitker, Morgan Roupret;
Department of Urology, Hôpital Tenon, and the CeRePP National Group, Paris, France; Urology, Paris 6
University, Paris, France; Urology University Paris 6, Paris, France
Abstract:
Background: Definition of LRPC and candidates for AS remains problematic. Relevant markers that reflect
tumor aggressiveness are still to be determined. When AS is used it can be difficult to assess disease
progression despite surveillance with PSA and repeat biopsies. Moreover, 20-50% of patients on AS were
over the windows of curability when radical treatment was triggered. The current knowledge of PC suggests
that aggressiveness should be assessed not only in terms of clinical features but also in terms of response to
Androgen Deprivation Therapy (ADT). Methods: 83 men with LRPC (T1c or T2a PC; PSA ≤10ng/ml;
Gleason score ≤6) whom have chosen prostate cancer management without radical therapy were included.
They then underwent AS after receiving one injection of ELIGARD-22.5. AS consisted of PSA every 3
months (mo) and biopsies (≥12 cores) every 12mo. Patients were stratified at diagnosis according to age at
diagnosis, PSA, PSA density, PSA nadir, bio-testosterone, dynamic MRI staging, % positive cores and
length of tumor on the diagnosis biopsy. Predictive factors of recurrent PC observed on biopsy were tested
using a Cox regression and Markov models. Results: Mean age at diagnosis of LRPC was 64 years,
(standard deviation, 6.2 years). Median time to follow-up after diagnosis biopsy was 31mo. Surveillance
biopsies were positive for 37 men (44%) (7 with Gleason score>6). In the subgroup of insignificant PC
according EPSTEIN criteria surveillance biopsies were positives for 17/48 men (35%) (2 with Gleason
score>6). Expected results from literature on classical AS were 60-70% of positive biopsy and 10-21% of
upgraded biopsy at the first repeat biopsy. Predictive factors of prostate cancer observed on biopsy were:
PSA nadir at 3mo <0,1ng/ml (OR=1.8; 95%CI 1.0 to 3.3 p=0.04), positive core biopsy>1(OR=1.7; 95%CI 1.0
to 2.9; p=0,03), and >T1c detectable tumor on MRI (OR=2.9; 95%CI 1.4 to 5.9; p=0.003). Conclusions:
Results obtained with 3mo of LHRHa for LRPC suggest that ADT response can be used firstly to reduce
prevalence of primary PC lesions and secondly in order to identify PC able to castration resistance and
consequently which require radical treatment.
Osteoporosis screening among prostate cancer survivors treated with androgen deprivation therapy.
Abstract No:6045
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 6045)
Author(s): Alicia Katherine Morgans, Matthew Raymond Smith, A. James O'Malley, Nancy Lynn Keating;
Massachusetts General Hospital Cancer Center, Boston, MA; Harvard Medical School, Department of Health
Care Policy, Boston, MA; Harvard Medical School, Boston, MA
Abstract:
Background: Androgen deprivation therapy (ADT), the standard systemic treatment for prostate cancer, has
adverse effects including bone loss and fractures. Current national guidelines suggest that men receiving
ADT undergo dual energy x-ray absorptiometry (DXA) before and during ADT to better characterize fracture
risk. We assessed receipt of DXA testing in a population-based cohort of men treated continuously with ADT
for at least 1 year and identified factors associated with testing. Methods: Using Surveillance, Epidemiology,
and End Results-Medicare data, we identified men aged >65 with local or regional prostate cancer
diagnosed during 2001-2007 and followed through 2009 who received at least 1 year of continuous ADT. We
identified receipt of DXA testing in the 18-month period beginning 6 months before the first dose of ADT. We
used logistic regression to identify factors associated with DXA testing, including patient and tumor
characteristics and the physicians with whom they had outpatient visits. Results: Among 28,960 men treated
with ADT for ≥1 year, 6.5% had at least one DXA scan from 6 months before the first dose of ADT through 1
year after. DXA testing increased over time, with men initiating ADT in 2007-2009 more likely to be tested
than those treated in 2001-2002 (10.0% vs. 3.4%, OR 2.29, 95% CI 1.83-2.85). Men aged ≥85 were less
likely than men aged 66-69 to undergo testing (OR 0.76, 95% CI 0.65-0.89). Black men were less likely than
white men to undergo testing (OR 0.92, 95% CI 0.61-0.86), as were men living in areas with lower
educational attainment (P<.001). Compared with men seeing a urologist but no medical oncologist or primary
care provider (PCP), men seeing a medical oncologist and a urologist (OR 2.11, 95% CI 1.39-3.21) and
those seeing a medical oncologist, urologist and PCP (OR 2.59, 95% CI 2.01-3.34) had higher odds of
testing. Conclusions: Few men receiving ADT for prostate cancer undergo DXA testing, with particularly low
rates of testing among older men, black men, and those living in areas with low educational attainment.
Visits with a medical oncologist were associated with increased odds of testing. Interventions are needed to
increase bone density testing among men receiving long-term ADT.
EXCAP exercise to improve fatigue, cardiopulmonary function, and strength: A phase II RCT among
older prostate cancer patients receiving radiation and androgen deprivation therapy.
Abstract No:9010
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 9010)
Author(s): Karen Michelle Mustian, Lisa Sprod, Michelle Christine Janelsins, Luke Joseph Peppone, Supriya
Gupta Mohile, Lara Anne Trevino, Jennifer S. Gewandter, Kavita Dayal Chandwani, Charles E Heckler, Gary
R. Morrow; University of Rochester Medical Center, Rochester, NY
Abstract:
Background: Radiation therapy (RT) and androgen deprivation therapy (ADT) result in cancer-related
fatigue (CRF), decreased cardiopulmonary function (CPF) and decreased strength. Research suggests
exercise can improve CRF during RT and ADT, through physical conditioning responses that improve CPF
and strength. We explored the influence of an individually-tailored, home-based exercise intervention
(EXCAP), including progressive resistance and aerobic training, on CRF, CPF and strength. Methods: Older
prostate cancer patients (N=58; mean age=67), receiving RT (47%) or ADT (53%), were randomized to 6
wks of EXCAP (7 days/wk) or standard care (RT or ADT with no exercise). CPF (VO2 max) was assessed
via graded exercise testing (GXT) or a 6-minute walk test when GXT was contraindicated. Muscular strength
was assessed using multiple repetition maximum testing (chest press and leg extension). CRF was
assessed via valid self-report questionnaires (BFI, POMS-FI, MFSI). All assessments were pre- and postintervention. Results: ANCOVAs, controlling for baseline, revealed significant differences between groups in
mean levels of CRF on the BFI and POMS-FI (all p<0.05), and a trend toward differences on the MFSI
(p<0.10) with significant baseline interactions (all p<0.05) post-intervention: exercisers decreased CRF while
controls increased. ANCOVAs revealed a trend toward differences between groups in mean levels of CPF
(VO2 max) and strength (all p<0.10): exercisers improved while controls declined in performance. Pearson
correlations revealed significant inverse associations between changes in CRF (BFI) and CPF (p<0.05;r=0.0.36), and CRF and strength (p<0.05;r=-0.0.31). MANOVA revealed that changes in CPF and strength
significantly predicted changes in CRF (p<0.05, r=0.67) and accounted for 45% of the variance.
Conclusions: Exercise improves CRF and these improvements may be mediated, in part, by improvements
in CPF and strength. Future phase III RCTs with prostate cancer patients receiving RT and ADT are needed
to confirm these relationships. Funding: DOD W81XWH-07-1-0341, NCI K07CA120025, NCI
1R25CA102618.
Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic
prostate cancer (HSM1PC) patients (pts): Results of S9346 (INT-0162), an international phase III trial.
Abstract No:4
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4)
Author(s): Maha Hussain, Catherine M. Tangen, Celestia S. Higano, E. David Crawford, Glenn Liu, George
Wilding, Stephen Prescott, Atif Akdas, Eric Jay Small, Nancy Ann Dawson, Bryan J Donnelly, Peter Venner,
Ulka N. Vaishampayan, Paul F. Schellhammer, David I. Quinn, Derek Raghavan, Nicholas J. Vogelzang, Ian
Murchie Thompson; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; SWOG Statistical
Center, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Colorado Health
Science Center, Aurora, CO; University of Wisconsin Carbone Cancer Center, Madison, WI; St. James
University Hopsital, Leeds, United Kingdom; Marmara University, Istanbul, Turkey; University of California,
San Francisco, San Francisco, CA; Georgetown Lombardi Comprehensive Cancer Center, Washington, DC;
Prostate Cancer Institute, Calgary, AB, Canada; Cross Cancer Institute, Edmonton, AB, Canada; Karmanos
Cancer Institute, Wayne State University, Detroit, MI; Urology of Virginia, Norfolk, VA; University of Southern
California Norris Comprehensive Cancer Center, Los Angeles, CA; Carolinas Medical Center, Charlotte, NC;
US Oncology Research, LLC, McKesson Specialty Health, The Woodlands, TX, and Comprehensive Cancer
Centers of Nevada, Las Vegas, NV; University of Texas Health Science Center at San Antonio, San Antonio,
TX
No abstract text available
Guideline-discordant androgen deprivation therapy (ADT) use in localized prostate cancer (CaP) and
cost implications: A population-based study.
Abstract No:4647
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4647)
Author(s): Adam Rea Kuykendal, Laura H Hendrix, Ramzi George Salloum, Paul Alphonso Godley, Ronald
C. Chen; University of North Carolina at Chapel Hill, Chapel Hill, NC
Abstract:
Background: ADT use in localized CaP has increased overall survival and is recommended by National
Comprehensive Cancer Network (NCCN) guidelines in certain clinical situations. However, ADT may cause
harm and is without benefit in other situations. Prior studies showed a decline in “inappropriate” ADT use
coinciding with Medicare reimbursement changes in 2004-2005. This study examines recent trends in ADT
use and quantifies the cost of guideline-discordant ADT. Methods: Patients in the Surveillance Epidemiology
and End Results (SEER)-Medicare database diagnosed with non-metastatic CaP between 2004 and 2007,
ages 66-80 were included for analysis. PSA, Gleason score and clinical stage were used to define D’Amico
risk categories. Logistic regression was used to examine factors associated with guideline-discordant ADT
use. Annual direct cost was estimated using the current Medicare reimbursement amount for ADT. Results:
Of 24,280 men included, 13% received guideline-discordant ADT. Discordant use declined from 15% in 2004
to 11% in 2007. In low-risk patients, 15% received discordant ADT, mostly due to simultaneous ADT with
radiation. Discordant use was seen in 7% of intermediate and 16% of high-risk patients, mostly from ADT
monotherapy. African American (AA) (p<.001), older patients (p<.001) and those with more comorbidities
(p<.001) were more likely to receive discordant ADT (Table). The estimated annual direct cost to Medicare
from discordant ADT is $43,500,000. Conclusions: Approximately one in eight patients received ADT
discordant with published guidelines, with AA and elderly patients disproportionately affected. Elimination of
discordant use would result in substantial savings in healthcare costs.
Covariate
OR p value
AA (vs. Caucasian)
1.35 <.001
Age (vs. 65-69)
70-74
1.58 <.001
75-79
3.22 <.001
Modified Charlson comorbidity (vs. 0)
>0
1.34 <.001
Diagnosis (vs. 2004)
2005
.86 .008
2006
.78 <.001
2007
.71 <.001
Risk group (vs. low risk)
Intermediate
.40 <.001
High
.88 .003
Controls for SEER region, regional socioeconomic indicators, and marital status.
Prevalence of nonmetastatic (M0) prostate cancer (PC) patients on continuous androgen deprivation
therapy (ADT) in the United States.
Abstract No:4659
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4659)
Author(s): Karynsa Cetin, Shuling Li, Anne Hudson Blaes, Scott Stryker, Alexander Liede, Thomas J.
Arneson; Center for Observational Research, Amgen Inc, Thousand Oaks, CA; Chronic Disease Research
Group, Minneapolis, MN; University of Minnesota, Minneapolis, MN
Abstract:
Background: ADT is the cornerstone treatment of metastatic PC, but the nature and extent of its use in the
M0 setting is less well-described. We sought to estimate the current prevalence of M0 PC patients actively
receiving continuous ADT (≥6 months) in the US. Methods: Two point-prevalent cohorts on 12/31/2008 with
continuous insurance coverage in 2008 were assembled: men aged 45-64 years (yrs) enrolled in commercial
health plans (MarketScan) and men aged ≥67 yrs enrolled in fee-for-service (FFS) Medicare (Medicare 5%
sample). Among those with evidence of PC and no evidence of metastases, we selected men who had
continuous exposure to gonadotropin-releasing hormone agonists during at least the last 6 months of 2008
or received bilateral orchiectomy prior to 7/1/2008. The number of prevalent ADT users was extrapolated to
the entire national commercially insured population aged 45-64 yrs and to the entire Medicare FFS
population aged ≥65 yrs using person-level weights. Applying age-specific prevalence estimates to the US
Census population on 12/31/2008, we estimated the number of prevalent ADT users in the total US male
population aged ≥45 yrs. Results: An estimated 11,935 (95% confidence interval [CI]: 11,310-12,561)
commercially insured men aged 45-64 yrs and 115,468 (95% CI: 112,304-118,633) Medicare FFS men aged
≥65 yrs were M0 PC patients actively receiving continuous ADT for ≥6 months on 12/31/2008. Extrapolated
to the total US male population aged ≥45 yrs, this estimate was 188,916 (95% CI: 184,104-193,727). Agespecific prevalence (N [95% CI]) on 12/31/2008 is presented in the table. Conclusions: We projected nearly
190,000 US men with M0 PC were actively receiving continuous ADT for ≥6 months at the end of 2008, and
the vast majority (91%) of these men were aged ≥65 yrs. Additional work will address timing of initiation,
duration, and other aspects of ADT use in this large population of M0 PC patients.
Age, yrs Commercial and FFS Medicare males
US males
45-64
11,935 (11,310-12,561)
17,163 (16,264-18,062)
65-74
28,087 (26,272-29,902)
43,851 (41,017-46,686)
75-84
51,541 (49,549-53,532)
76,157 (73,214-79,100)
≥85
35,841 (34,195-37,487)
51,745 (49,368-54,121)
A randomized, open-label, phase II study of MDV3100 alone or in combination with leuprolide and
dutasteride as neoadjuvant therapy to prostatectomy in intermediate and high-risk prostate cancer.
Abstract No:TPS4695
Citation:
J Clin Oncol 30, 2012 (suppl; abstr TPS4695)
Author(s): Robert B. Montgomery, Anthony Joshua, Alison L. Hannah, Amy C. Peterson, Christian Lopez,
Martin Edwin Gleave, Mary-Ellen Taplin; University of Washington School of Medicine, Seattle, WA; Princess
Margaret Hospital, Toronto, ON, Canada; Medivation, Inc., San Francisco, CA; University of British
Columbia, Vancouver, BC, Canada; Dana-Farber Cancer Institute, Boston, MA
Abstract:
Background: MDV3100 is a potent androgen receptor (AR) signaling inhibitor (ARSI) that inhibits AR
signaling via three mechanisms: inhibition of androgen binding to AR, inhibition of AR nuclear translocation,
and inhibition of nuclear AR-DNA binding. In vivo, MDV3100 induces significant prostate cancer apoptosis,
an effect not seen with anti-androgens. To date, the use of neoadjuvant androgen deprivation therapy has
not led to an improvement in time to PSA progression (Soloway 2002; Aus 2002). While serum androgens
may be suppressed using luteinizing hormone-releasing hormone agonists, intratumoral levels of androgens
remain, driving continued AR signaling and prostate cancer survival. More effective inhibition of AR signaling
may improve local and systemic disease control. Methods: MDV3100-07 will assess the effect of 6 mos of
neoadjuvant AR blockade with AR inhibition alone (MDV3100) or in combination with maximal suppression
of androgens (MDV3100 +leuprolide [L] + dutasteride [D]). Eligible patients will have treatment-naive
localized prostate cancer and be candidates for radical prostatectomy. Patients must have either PSA > 10
ng/mL or Gleason score ≥ 7 (4 + 3) with ≥3 cores containing tumor. Patients with evidence of
metastatic/nodal disease are excluded. All patients receive MDV3100 (160 mg/d PO); those randomized to
MDV3100+L+D therapy also receive L (22.5mg IM q3m) and D (0.5 mg/day PO). Serum/tumor androgen
levels will be serially assessed. Tissue from the diagnostic and prostatectomy specimens will be evaluated
for androgen levels, AR signaling profiles, and selected markers of apoptosis and mitotic indices. The
primary efficacy endpoint is pathological complete response (pCR) rate at time of radical prostatectomy. For
each arm, the percent of patients who achieve a pCR will be compared to the percent pCR in patients
treated with neoadjuvant leuprolide, estimated to be 5% in a mixed low-to-intermediate risk population.
Target Accrual: 40 pts will be randomized 1:1 to MDV3100 or MDV3100+L+D therapy. Keywords:MDV3100,
prostate cancer, androgen receptor, anti-androgen, Phase 2, neoadjuvant.
Association of metabolic syndrome with poorer prostate cancer and overall survival in men receiving
androgen deprivation therapy (ADT) for biochemical relapse.
Abstract No:4555
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4555)
Author(s): Sarah Maria Rudman, Kathryn P. Gray, Julie Kasperzyk, Edward Giovannucci, Michael Pitt,
Massimo F. Loda, Lorelei Mucci, Christopher Sweeney; Division of Cancer Studies, King's College London,
Guy's Hospital, London, United Kingdom; Dana-Farber Cancer Institute, Boston, MA; Harvard School of
Public Health, Boston, MA; Channing Laboratory, Department of Medicine, Harvard Medical School, Boston,
MA; Department of Medical Oncology, Dana Farber Cancer Institute, Department of Pathology, Brigham and
Women's Hospital and Kings College, Boston, MA
Abstract:
Background: The metabolic syndrome (MS) has been implicated in the development of prostate cancer
(PC). In our previous study of a Veterans’ Administration (VA) cohort, MS was associated with a shorter
duration of PC control with ADT. We report the impact of MS on overall survival (OS) and PC specific death
for a cohort of patients with biochemical relapse. Methods: 273 pts (64 VA pts and 209 pts from Health
Professionals Follow up Study) treated with ADT for biochemical recurrence post radiation or prostatectomy
for PC were included. The modified Adult Treatment Panel III criteria for MS was used to identify patients
with MS status prior to the commencement of ADT. Cox models tested for association of MS status with OS
or time to PC specific death. With 42% overall death rate, 31% MS prevalence, there was 90% power to
detect HR= 1.81 (type I error rate =0.05). Results: 31% pts (84/273) had MS and 15% pts (40/273) died of
PC. Median follow-up was 9.5 years. The median OS with and without MS was 7.4 and 11.2 years
respectively. Patients with hypertension, being African American, having diabetes and age were associated
with increased risk of death from any causes, while hypertension and being African American were also
associated with increased risk of PC specific death. A multivariate Cox regression model adjusted for age at
diagnosis, race, definitive local therapy (RT vs. RP), PSA at diagnosis and Gleason score revealed MS was
associated with a significantly increased risk of death from any cause and PC specific death (Table).
Conclusions: In men receiving ADT for biochemically recurrent androgen dependent PC, the presence of
MS at the commencement of ADT is associated with an increased risk of death from any cause as well as
prostate cancer specifically.
Overall (N=273)
Comparison
Endpoint
(MS status) Median (years) Event Adjusted HR P value*
OS, (95%CI) (patient) (95% CI)
11.17
OS
No (ref)
74 (189) 1
(10-13.9)
2.12
Yes
7.42 (5.33-12.1) 40 (84)
<0.001
(1.42, 3.16)
PCa death No (ref)
25 (189) 1
2.03
Yes
0.036
15 (84)
(1.05, 3.94)
Cytoreduction and androgen signaling modulation by abiraterone acetate (AA) plus leuprolide
acetate (LHRHa) versus LHRHa in localized high-risk prostate cancer (PCa): Preliminary results of a
randomized preoperative study.
Abstract No:4556
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4556)
Author(s): Eleni Efstathiou, John W. Davis, Patricia Troncoso, Mark Anton Titus, Anh Hoang, Sijin Wen,
Amado J. Zurita, Namphuong Tran, Arturo Molina, Christopher Logothetis; University of Athens, Athens,
Greece; University of Texas M. D. Anderson Cancer Center, Houston, TX; University of Texas M. D.
Anderson Cancer Center, Houston, TX; Roswell Park Cancer Institute, Buffalo, NY; Janssen Research &
Development, Los Angeles, CA
Abstract:
Background: Endocrine to “intracrine” androgen signaling transition, a milestone in the lethal progression of
PCa, has not been characterized in localized high risk disease. Signaling heterogeneity under the selective
pressure of castration may account for response differences. Methods: A single institution preoperative
study of 12 weeks AA 1g/prednisone 5 mg + LHRHa compared to LHRHa (randomized 2:1) was conducted
in patients (pts) with high risk PCa (clinical stage ≥T1c and biopsy Gleason score ≥8, or ≥T2b, Gleason ≥ 7
and PSA > 10ng/ml). Primary aim: Assess difference in down staging (≤ ypT2) and safety. Secondary aims:
Assess difference in androgen biosynthesis, androgen signaling (AR, AR variants, NKX 3.1, ERG, PSA)
proliferation apoptosis and candidate treatment resistance pathways. Results: We report on 37 (50 enrolled)
pts who had prostatectomy. AA+LHRHa was given to 25pts, LHRHa to 12. Median age is 61 ys (46-74).
Preoperative PSA was <0.1ng/ml in 17/25 (68%) AA+LHRHa vs 0/12 LHRHa (p 0.0001). ypT2N0 occurred in
15/25 (60%) AA+LHRHa treated pts vs 4/12 (33%) LHRHa (p 0.17). Near complete cytoreduction (<6mm
scattered cells) occurred in 6/25 (24%) AA+LHRHa vs 1/12 (8%) LHRHa. Lymph node infiltration in 7/25
(28%) AA+LHRHa vs 6/12 (50%) LHRHa. Margin positivity in 2/25 (8%) AA+LHRHa vs 4/12 (33%) LHRHa (p
0.07). Grade 3 AA related AEs: elevated AST/ALT 4 (discontinued AA), hypertension 3. One AA+LHRHa pt
had postop pulmonary embolism. Androgen signaling and proliferation suppression is more profound in
AA+LHRHa treated remaining tumor cells (Table). Conclusions: Addition of AA to LHRHa results in greater
cytoreduction, suppression of PSA and androgen signaling compared to LHRHa in high risk PCa. Findings
support the hypothesis that intracrine androgen signaling is a therapy target in patients with untreated PCa
and form the foundation for a marker driven treatment strategy.
Mean tumor expression (involvement)% by IHC (standard deviation).
Marker
AA+LHRHa
LHRHa
P value Wilcoxon
AR
0.0001
27 (26)
69 (22.3)
Nkx3.1
0.002
50 (29.8)
83 (14.3)
CYP17
0.13
64 (22)
75 (14.4)
Ki67
0.003
3.4 (5)
8.6 (5.7)
Preliminary quality-of-life outcomes for SWOG-9346: Intermittent androgen deprivation in patients
with hormone-sensitive metastatic prostate cancer (HSM1PC)—Phase III.
Abstract No:4571
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 4571)
Author(s): Carol Moinpour, Donna Lynn Berry, Benjamin Ely, Catherine M. Tangen, Celestia S. Higano, Joel
Picus, Paul F. Schellhammer, Eila C. Skinner, Michael L. Cher, Ian Murchie Thompson, Maha Hussain; Fred
Hutchinson Cancer Research Center, Seattle, WA; Dana-Farber Cancer Institute, Boston, MA; SWOG
Statistical Center, Seattle, WA; Puget Sound Oncology Consortium/Seattle Cancer Care Alliance/University
of Washington, Seattle, WA; Siteman Cancer Center, Washington University School of Medicine, St. Louis,
MO; Eastern Virginia Medical School/Urology of Virginia, Norfolk, VA; USC Institute of Urology, University of
Southern California, Los Angeles, CA; Karmanos Cancer Institute, Wayne State University, Detroit, MI;
University of Texas Health Science Center at San Antonio, San Antonio, TX; University of Michigan
Comprehensive Cancer Center, Ann Arbor, MI
Abstract:
Background: The relative quality of life (QOL) for patients with newly diagnosed, metastatic prostate cancer,
treated with intermittent androgen deprivation (IAD) has been assumed and hypothesized, yet never
compared in a well-powered randomized trial (RT) to continuous androgen deprivation (CAD). SWOG-9346
provided such a RT in which to test QOL differences between CAD and IAD in men with metastatic prostate
cancer. Methods: Patients were randomized to CAD or IAD. Patients completed the SWOG QOL
Questionnaire (SF-20/SF-36, Symptom Distress Scale, treatment-specific symptoms, global QOL) at
randomization and months (mo) 3, 9, and 15 post-randomization. Five QOL change scores at one time point
(mo 3) were designated as primary for the QOL endpoint and are reported in this abstract: impotence, libido,
energy/vitality (E/V), physical function (PF), and emotional function (EF). Significance level was adjusted for
5 comparisons (used p=0.01). Results: 615 patients in the CAD arm and 633 in the IAD arm completed the
QOL questionnaire at baseline. Change between baseline and 3 months differed for the two arms with CAD
reporting statistically significantly more impotence and less libido than IAD. EF was also slightly better for the
IAD arm. Conclusions: These results indicate better sexual function in men receiving IAD versus CAD
through post-randomization month 3. Additional benefits for IAD may include better PF, E/V and EF.
Ongoing analyses will address the role of missing data, additional follow-up assessments, and resumption of
therapy in the IAD arm.
Descriptive results
Baseline treatment arm
3-mo
CAD IAD CAD IAD T-test p values*
Impotence %
.85 .82 .87 .73
< 0.01
(n)
(546) (585) (487) (494)
Libido %
.03 .04 .04 .11
< 0.01
(n)
(560) (580) (481) (486)
EF^ score
80.0 77.9 79.0 79.6
< 0.01
(n)
(568) (595) (491) (500)
PF^ score
70.2 70.7 69.3 71.3
0.08
(n)
(569) (591) 489) (500)
E/V^ score
59.8 59.7 58.9 60.0
0.23
(n)
(557) (586) (478) (489)
*T-test of arm difference in baseline to 3-month change for patients with both assessments; ^0-100 scale.
A phase I study of EP-100, a luteinizing hormone releasing hormone (LHRH) ligand conjugated to a
synthetic cytolytic peptide in patients with advanced refractory LHRH- receptor (R)-expressing
tumors.
Abstract No:3060
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 3060)
Author(s): Ramesh K. Ramanathan, Manpreet Chadha, John Sarantopoulos, Donald W. Northfelt, Glen J.
Weiss, Monica M. Mita, Kerry M. Barnhart, John Whisnant, Carola Leuschner, Hector Alila, Kelly Kevelin
Curtis; Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ; Institute for Drug
Development, Cancer Therapy and Research Center, University of Texas Health Science Center, San
Antonio, TX; Mayo Clinic, Scottsdale, AZ; Virginia G. Piper Cancer Center at Scottsdale Healthcare,
Scottsdale, AZ; Institute for Drug Development, University of Texas Health Science Center, San Antonio, TX;
Transmed Ventures, LLC, Cave Creek, AZ; Esperance Pharmaceuticals, Inc., Baton Rouge, LA; Mayo Clinic
Arizona, Scottsdale, AZ
Abstract:
Background: EP-100 is a synthetic 28 amino acid LHRH peptide conjugated to an 18 aa cytolytic peptide.
Selective targeting in LHRH-R expressing cells occurs via direct binding to the extracellular membrane
receptor followed by disruption of the membrane by the cytolytic peptide portion. A first in human, phase I
study was performed. Methods: Eligible pts had adequate organ function and LHRH-R tumor expression, as
determined by IHC. EP-100 was given IV (30-60 min) weekly x 3 for cohorts 1- 6 (n=20 at 0.6 - 5.2 mg/m2)
and then twice weekly x 3 for cohorts 7- 11 (n=18 at 7.8 - 40 mg/m2) with a week break. The
pharmacokinetic profile of EP-100 and antibody production against EP-100 was determined by a validated
HPLC/MS and ELISA respectively. Potential activity of EP-100 on the pituitary gonadotropes was determined
by plasma LH and FSH. Results: We screened 97 pts, archival tumor tissue obtained from 81 pts; 53 (65%)
were positive for LHRH-R, of which 37 were enrolled (female 76%) and treated. The LHRH-R expression
rate in breast was 81% (N=21) and in ovarian cancer 56% (n=18). Most pts had breast (n= 16, 42%) ovary
(n=7,18%), colon (n=4, 11%) or uterine (n=3, 8%) cancer. Pts were treated in a 3 + 3 standard dose
escalation scheme. Doses were escalated 100% in the absence of a grade 2 drug related toxicity. MTD was
not reached at the highest dose level of 40 mg/m 2. Only one DLT occurred, a grade 2 increase in ALT/AST.
The only other drug-related toxicity was a self limited infusion-related skin reaction (grade 1-2) in 10 pts. EP100 was rapidly cleared from circulation, mean half life ranged from 7.1 ± 3.8 min to 15.9 ± 3.6 min. Best
response was stable disease for >12 weeks in 5 pts. In 3 pts rapid, sustained decreases in LH/FSH levels
were noted. Antibody production against EP-100 was absent in all pts. Conclusions: The study has
completed accrual, the phase II dose is 30-40 mg/m2 twice a week x 3 weeks.EP-100is safe, well tolerated
and not antigenic/immunogenic. Preclinical studies indicated synergy with paclitaxel and doxorubicin. A
phase II study of EP-100 plus paclitaxel in ovarian cancer is planned.
Utilization of bone densitometry and administration of bisphosphonates to prevent osteoporosis in
patients with nonmetastatic prostate cancer receiving anti-androgen therapy.
Abstract No:6099
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 6099)
Author(s): Muhammad Atif Khan, Abby E Holt, Swetha Gujja, Rangaswamy Govindarajan; University of
Arkansas for Medical Sciences Hospital, Little Rock, AR; Arkansas Department of Health, Little Rock, AR;
University of Arkansas for Medical Sciences, Little Rock, AR
Abstract:
Background: Prostate cancer subjects with PSA relapse who are treated with androgen deprivation therapy
(ADT) are recommended to have baseline and serial bone densitometry (BD) and receive intravenous
bisphsphonates (BP). Utilization of BD and BP therapy was evaluated in a retrospective SEER Medicare
database analysis. Methods: A cohort study of men aged aged ≥ 65 years with a nonmetastatic incident
diagnosis of prostate cancer between 2004 and 2008 was conducted. Data were obtained from the
Surveillance, Epidemiology and End Results (SEER) linked Medicare claims. Medicare claims were used to
select prostate cancer cases who had ever received ADT and intravenous BP as part of their treatment. ADT
was defined as an orchiectomy, goserelin, leuprolide, leuprolide implant, or triptorelin. BD and treatment with
pamidronate or zoledronic acid were identified using Medicare HCPCS codes. One-sided exact binomial test
of proportion was used to determine if the physician compliance rate is consistent with 80%; meaning equal
to or higher than 80%. Results: 157,974 newly diagnosed prostate cancer cases were identified. Of those,
100,865 were age 65 and above and had no bone metastases. Subjects who did not have ADT claims were
excluded. 30,846 patients were eligible for analysis. Cases were further stratified by use of BD and BP
therapy. Results revealed 86.8% (N=26,774) on ADT did not receive either a BD or intravenous BP therapy.
Approximately 2.9% (N=885) of the cases on ADT received BP treatment without ever receiving a BD. 9.3%
(N=2,863) of the cases on ADT received a BD without receiving intravenous BP, while only 1.05% (N=324)
of the cases on ADT received both a BD and BP. A compliance rate of 1.05%, those patients receiving both
bone densitometries to screen for bone loss and preventive therapy, was well below the expected rate of
80%. Conclusions: Contrary to the recommendations, BD assessment and BP use is under utilized in men
receiving ADT for non metastatic prostate cancer. Education of practicing physicians regarding better
screening and preventative measures for osteoporosis in this population is warranted.