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AUA NEWS
| THE OFFICIAL NEWSMAGAZINE OF THE AMERICAN UROLOGICAL ASSOCIATION |
2014 ANNUAL
MEETING HIGHLIGHTS
Castration Resistant Prostate
Cancer
Course #011IC
Establishing an Advanced Prostate Cancer
Clinic: A Guide for the Community Urologist
Course #023IC
AUA Guideline: Castration Resistant Prostate
Cancer Update
Course #051IC
Managing Metastatic Prostate Cancer in Your
Urology Practice: Coding and Science
Course #078IC
Sequencing Novel Agents in Advanced
Prostate Cancer 2014: Case Based Key
Knowledge for Urologists
Abstract Highlight
HIGHLIGHTS
AUANews Editor
Gopal H. Badlani, MD
Castration Resistant
Publisher
Prostate Cancer
American Urological Association
1000 Corporate Boulevard
Linthicum, MD 21090
Cr
information and comparison with the recommenda-
tions of the authorities.
E
CM
AUA 2014 ORLANDO, FL ANNUAL MEETING HIGHLIGHTS 1
CMEINFORMATION
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AUA 2014 ORLANDO, FL ANNUAL MEETING HIGHLIGHTS 3
CMEInformation
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P. George Febbo, MD ity may contain reference(s) to off-label
Course #078IC: Sequencing Novel Chief Medical Officer or unapproved uses of drugs or devices.
Agents in Advanced Prostate Can- Genomic Health, Inc Please consult the product prescrib-
cer 2014: Case Based Key Knowl- San Francisco, CA ing information for full disclosure of
edge for Urologists Disclosures: Nothing to disclose approved uses.
COURSE #011IC
Establishing an Advanced Prostate Cancer Clinic: A
Guide for the Community Urologist
Basir U. Tareen, MD, Course Director; Gregory R. Hanson, MD and Raoul S. Concepcion, MD, Faculty
Introduction sipuleucel-T, which is infused back into nurse champion who will be in charge
the patient during a series of 3 infusions of scheduling and coordinating the leu-
Advanced prostate cancer treatment has (each 2 weeks apart), and uses the bodys kapheresis visits at the American Red
seen a dramatic shift in its treatment T cells to proliferate and fight disease. In Cross, the office infusions, and assisting
paradigm during the last 3 years. The with all the paperwork, prior authoriza-
the landmark IMPACT (Identification
advent of several new drugs has revo- tions and insurance issues.
of Men with a genetic predisposition
lutionized the urologists ability to treat
to ProstAte Cancer) trial 512 patients
this disease and prolong life. With these Oral Agents in Community Practice
were randomized to placebo vs treat-
new therapeutic modalities the commu-
ment.1 Patients treated with sipuleucel-T Oral therapies have been used in
nity urologist has the opportunity to be
had a 4.1-month survival advantage vs advanced prostate cancer for many
the primary physician in a disease that
placebo with a 22% relative risk reduc- years, albeit with limited success and
has historically been managed by our
tion in death. often with significant side effects. Recent-
field.
Establishing a clinic in your office ly 2 newer agents were approved for use
The Changing Landscape is not as complicated as one would in metastatic CRPC. These agents have
expect. The greatest task at the outset is seen rapid acceptance into the com-
Before 2010 the mainstay of advanced identifying appropriate patients, namely munity urologists arsenal due to their
prostate cancer treatment was hormon- those with asymptomatic or minimally efficacy in the pre-chemotherapy setting
al therapy and later cytotoxic chemo- symptomatic metastatic CRPC. When as well as their tolerability profiles.
therapy. In 2010 the U.S. Food and preparing to start an infusion clinic we Abiraterone is an oral therapy that
Drug Administration (FDA) approved recommend identifying several of these inhibits the CYP17A1 enzyme in the ste-
sipuleucel-T for use in patients with patients by flagging them in the months roid biosynthesis pathway. Abiraterone
metastatic castration resistant prostate before opening the infusion clinic or was first approved in April 2011 for
cancer (CRPC). This was soon followed doing a more formal data dive with your post-chemotherapy CRPC followed by
by the approval of abiraterone and electronic medical record (EMR) soft- approval for pre-chemotherapy use in
enzalutamide, 2 oral agents that have ware. December 2012. The use of abiraterone
both been shown to extend survival The simple setup includes a room you requires coadministration of prednisone
significantly. can make available in your office for 2 and metabolic monitoring, typically
In 2012 we saw the approval of radi- hours, a comfortable chair, an IV pole every 4 weeks.
um-223, the most recent therapy spe- and a nurse who can start an 18 gauge Enzalutamide is a second oral therapy
cifically for bone metastatic disease in IV. Most infusion clinics will consider that functions as an androgen receptor
prostate cancer. The addition of these having Demerol 15 mg on hand as antagonist. Current indications are for
new therapies has given urologists a well in case of a significant reaction. patients with metastatic CRPC with
newfound ability to continue point of From a financial standpoint sipuleucel- progression after chemotherapy, but it
care from diagnosis to the latest stages T can be a great benefit to the prac- has been used in the off-label setting in
of advanced disease. tice. Billing is done via an infusion patients who are not candidates for che-
code (96413 $500 per infusion) and motherapy. Approval of enzalutamide in
Establishing a Sipuleucel-T
the medication cost of $30,508 with the pre-chemotherapy setting is thought
Infusion Clinic
reimbursement of $32,070. Overall the to be imminent based on recent data pre-
Sipuleucel-T is a first of its kind drug net profit per infusion is approximately sented at AUA2014. Enzalutamide does
therapy that uses the bodys own den- $1,700 3 infusions or $5,100 per not require the concomitant use of ste-
dritic cells to target prostate cancer. patient treated. roids and the side effect profile is mild,
Leukapheresis is done and the patients We have found the key to a successful with seizures being the most concerning
own antigen presenting cells are exposed infusion clinic is identifying a physician (in fewer than 1% of patients).
to prostatic acid phosphatase. This com- champion whose role is to see all the Incorporating abiraterone and enzalu-
bination of prostatic acid phosphatase initial consults and to make sure the tamide into an advanced prostate cancer
and granulocyte-macrophage colony- patients are appropriately screened and clinic requires some initial setup. We
stimulating factor is the active agent in selected. Perhaps more important is a
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AUA 2014 ORLANDO, FL ANNUAL MEETING HIGHLIGHTS 5
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found that limiting the use of these Ultimately studies such as the PRE- Radium-223 in Community Practice
medications to 2 to 3 physicians who DICT trial will allow us to define the
manage advanced prostate cancer was ideal frequency of imaging in men with In 2013 the FDA approved radium-223
an important element. In addition, we M0 CRPC. In the meantime, all patients for use in men with prostate cancer
presented our other partners with cheat with M0 CRPC should have baseline bone metastases. With this novel agent
sheets on these medications to deal with imaging done, and repeat imaging based the radium mimics calcium and tar-
any on call concerns. We also designed on a change in symptoms, PSA doubling gets osteoblastic bone metastases. The
followup order sets through an EMR time, or at a reasonable frequency rang- ALSYMPCA trial showed an overall
system to ensure that patients received ing from every 3 months to every year, survival of more than 3 months in men
appropriate laboratory followup and depending on the patient and clinical treated with radium-223 vs placebo.3
clinic appointments. suspicion. Currently this therapy is delivered by
These medications can be expensive, radiation oncologists or nuclear medi-
typically costing $6,000 to $7,000 a Establishing a Bone Health Clinic cine radiologists. Use of this therapy is
month. We have worked closely with again dependent on urologists having
A well-known result of long-term andro- appropriate imaging on patients with
patient support options through phar- gen deprivation is its effect on bone
maceutical companies to help patients CRPC so that when they convert from
health and subsequent osteoporosis. A M0 to M1 they can be appropriately
with co-pay assistance. Our initial expe- decrease in circulating levels of testoster-
rience also necessitated finding specialty considered for radium-223 when symp-
one leads to decreased levels of estrogen, tomatic bone metastases develop.
pharmacies that could consistently sup- increased osteoclasts, decreased osteo-
ply these medications for our patients. blasts and increased RANK Ligand pro- Summary
duction.2
Role of Imaging in Advanced As urologists we are the experts in pros-
All patients starting long-term andro-
Disease tate cancer, the providers who see this
gen deprivation therapy should have a
The role of imaging in detecting meta- baseline DEXA scan. In addition, it is disease beginning with the increased
static disease has become increasingly ideal to have an extended care provider PSA, to biopsy, and to all stages of
important as the newer therapies (abi- focus on educating patients regarding treatment. It naturally holds that even
raterone, enzalutamide, sipuleucel-T diet (calcium) and exercise, and also once the disease progresses to advanced
and radium-223) require the presence to discuss pharmacological options for stages, urologists should continue to pro-
of documented metastatic disease for maintenance of bone health. vide high quality continuity of care.
approved use. Historical models which Bisphosphonates are a well-known 1. Kantoff PW, Higano CS, Shore ND et al: Sipu-
suggested only those with a prostate spe- class of drugs which have been used leucel-T immunotherapy for castration-resistant
prostate cancer. N Engl J Med 2010; 363: 411.
cific antigen (PSA) greater than 20 ng/ for this indication, although not FDA 2. Lipton A, Uzzo R, Amato RJ et al: The science
ml would have metastatic disease have approved for cancer treatment induced and practice of bone health in oncology: manag-
been changing with the use of sodium bone loss. More recently urologists have ing bone loss and metastasis in patients with solid
tumors. J Natl Compr Canc Netw, suppl., 2009; 7:
fluoride positron emission tomography successfully used denosumab/Prolia/ S1.
(PET) computerized tomography (CT) XGEVA, which is a human monoclo- 3. Parker C, Nilsson S, Heinrich D et al: Alpha emit-
ter radium-223 and survival in metastatic prostate
and C-11 acetate choline PET CT, as nal antibody that binds RANK Ligand cancer. N Engl J Med 2013; 369: 213.
these are significantly more sensitive and reduces osteoclast activity.
than a standard technetium-99m bone
scan.
6 AUA 2014 ORLANDO, FL ANNUAL MEETING HIGHLIGHTS
COURSE #023IC
COURSE #051IC
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AUA 2014 ORLANDO, FL ANNUAL MEETING HIGHLIGHTS 9
Course #051IC
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Clin Oncol (R Coll Radiol) 2013; 25: 406. denosumab on bone mineral density in men
Lupron Cost Reim- Annual 2. Kantoff PW, Higano CS, Shore ND et al: Sipu- receiving androgen deprivation therapy for pros-
Dose (US $) burse- Net leucel-T immunotherapy for castration-resistant tate cancer. J Urol 2009; 182: 2670.
prostate cancer. N Engl J Med 2010; 363: 411. 11. Michaelson MD, Kaufman DS, Lee H et al:
(mg) ment Profit 3. Ryan CJ, Smith MR, de Bono JS et al: Abiraterone Randomized controlled trial of annual zoledronic
(US $) (US $) in metastatic prostate cancer without previous che- acid to prevent gonadotropin-releasing hormone
motherapy. N Engl J Med 2013; 368: 138. agonist-induced bone loss in men with prostate
7.5 130 273.37 1,720.44 4. de Bono JS, Logothetis CJ, Molina A et al: Abi- cancer. J Clin Oncol 2007; 25: 1038.
22.5 390 679.03 1,156.12 raterone and increased survival in metastatic pros- 12. Rosen LS, Gordon D, Tchekmedyian S et al:
tate cancer. N Engl J Med 2011; 364: 1995. Zoledronic acid versus placebo in the treatment
30 520 881.86 1,085.58 5. Tran C, Ouk S, Clegg NJ et al: Development of a of skeletal metastases in patients with lung cancer
45 780 1,287.52 1,015.04 second-generation antiandrogen for treatment of and other solid tumors: a phase III, double-blind,
advanced prostate cancer. Science 2009; 324: 787. randomized trialthe Zoledronic Acid Lung Can-
This course highlighted the need 6. Scher HI, Fizazi K, Saad F et al: Increased survival cer and Other Solid Tumors Study Group. J Clin
with enzalutamide in prostate cancer after chemo- Oncol 2003; 21: 3150.
and the methods for urologists to con- therapy. N Engl J Med 2012; 367: 1187. 13. Smith MR, Saad F, Coleman R et al: Denosumab
tinue providing multidisciplinary care 7. Beer TM, Armstrong AJ, Rathkopf DE et al: and bone-metastasis-free survival in men with cas-
Enzalutamide in metastatic prostate cancer before tration-resistant prostate cancer: results of a phase
for patients with CRPC. The business chemotherapy. N Engl J Med 2014; 371: 424. 3, randomised, placebo-controlled trial. Lancet
aspects also showcased opportunities 8. Parker C, Nilsson S, Heinrich D et al: Alpha emit- 2012; 379: 39.
ter radium-223 and survival in metastatic prostate 14. Fizazi K, Carducci M, Smith M et al: Denosumab
and challenges in the field. cancer. N Engl J Med 2013; 369: 213. versus zoledronic acid for treatment of bone
9. Datta M and Schwartz GG: Calcium and vitamin metastases in men with castration-resistant prostate
1. Loblaw DA, Walker-Dilks C, Winquist E et al: D supplementation during androgen deprivation cancer: a randomised, double-blind study. Lancet
Systemic therapy in men with metastatic castra- therapy for prostate cancer: a critical review. 2011; 377: 813.
tion-resistant prostate cancer: a systematic review. Oncologist 2012; 17: 1171.
10. Smith MR, Saad F, Egerdie B et al: Effects of
COURSE #078IC
Sequencing Novel Agents in Advanced Prostate Can-
cer 2014: Case Based Key Knowledge for Urologists
Judd W. Moul, MD, FACS, Course Director; J. Kellogg Parsons, MD and P. George Febbo, MD, Faculty
It is an exciting time for physicians who tant drivers of the disease.3, 4 Although oncologists, as well as nurses and other
care for men with advanced prostate ADT has long been known to improve allied health professionals.
cancer and more importantly, it is a survival and offers an excellent progno- We have built our field on the prem-
more optimistic time for patients and sis, a significant number of patients lose ise that urology is a surgical and a
their families. Since 2010, 6 new agents responsiveness to surgical or medical medical specialty, and this blending of
have been approved by the Food and castration (ie castration resistant prostate disciplines is what has drawn many of
Drug Administration (FDA) for castra- cancer) with time. As a result, CRPC us to the specialty since its inception. As
tion resistant prostate cancer (CRPC), is associated with significant morbid- more consolidation takes place in the
including sipuleucel-T (Provenge), ity and mortality, and painful bone academic and private sectors, more large
cabazitaxel (Jevtana), abiraterone ace- metastases develop in more than 85% groups are designating subspecialty care.
tate (Zytiga), denosumab (XGEVA), of patients. It is critical for at least one partner to
enzalutamide (Xtandi) and radium-223 While the treatment goals of CRPC remain at the forefront of advanced
(Xofigo).1 With the exception of caba- include improving survival and miti- prostate cancer and to offer or assist in
zitaxel, these agents are commonly gating disease progression, these aims the offering of these new agents.
available for urologists and oncologists must be balanced with patient quality Of the 6 new medications 5
to prescribe. The new oral hormonal of life.5 CRPC is a heterogeneous dis- (sipuleucel-T, abiraterone, enzalutamide,
agents are particularly appealing for ease in which patients generally present denosumab, radium-223) are squarely
urological use since urologists have been with increasing prostate specific antigen in the realm of urology, being oral
at the forefront of androgen deprivation (PSA). These patients may have non- agents or parenteral agents under our
therapy (ADT) for more than 75 years.2 metastatic disease, asymptomatic meta- prescribing purview. Furthermore, many
Prostate cancer growth is initially static disease or symptomatic metastatic of us also embrace the multidisciplinary
highly dependent on circulating andro- disease. Therefore, current treatment management of prostate cancer and need
gens. However, in patients with dis- options for CRPC require a multidis- to be familiar with these agents to help
ease progression, androgen independent ciplinary approach that involves urolo- cement our expertise and relationship
pathways become increasingly impor- gists, radiation oncologists and medical with our medical oncology colleagues
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10 AUA 2014 ORLANDO, FL ANNUAL MEETING HIGHLIGHTS
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and partners. It is critical for us to know the jaw, while others believe that high course of CRPC when their immune
these agents to be able to contribute to risk men with new M1 bony disease system is the most robust. It is important
our patients best interest and care. deserve consideration for denosumab. to select patients for sipuleucel-T who
In this 2014 course we used a case Since denosumab is given as a subcu- have a 3 to 6-month window or longer
based and audience response system to taneous injection, does not affect renal before they will need chemotherapy or
create an interactive educational session function and does not require dose other treatment that might interfere with
on these new agents that urologists may adjustment for renal insufficiency, it is the immune system.
use in patients with CRPC in 2014. becoming more popular for urologists Most recently, Schellhammer et al
to administer. Since the drug can cause examined the response to sipuleucel-T
Degarelix hypocalcemia, urologists must check the by patient PSA at the start of this novel
Many contemporary patients with high serum calcium level before ordering treatment.7 In men who had a PSA in
risk M1 disease are initiated on ADT denosumab, and must ask patients to the lowest quartile of the IMPACT trial
with the pure gonadotropin-releasing take vitamin D and calcium supplements (less than 22 ng/ml), there was a more
hormone antagonist degarelix (FIRMA- while on denosumab. robust overall survival (OS) advantage
GON). This drug was approved by Finally, XGEVA is not approved to for sipuleucel-T. Specifically the esti-
the FDA in December 2008 and has treat men who do not have bone metas- mated 3-year survival for patients on
the advantage of lacking the testos- tases. However, there is a lower dose sipuleucel-T was 62.6% vs 41.6% for
terone surge or flare. We discussed of denosumab that is FDA approved to men randomized to the control arm
this agent and the latest clinical trial prevent bone loss (osteopenia and osteo- of the study. Since most patients with
results.6 Degarelix is commonly used as porosis) in men without bone metastases CRPC who have these lower PSA val-
a starter ADT agent because of the rapid who are taking LHRH for prostate can- ues are in the care of urologists, these lat-
response, lack of testosterone surge and cer. This 60 mg denosumab formulation est data place sipuleucel-T use squarely
lack of clinical flare. is called Prolia and it is given subcuta- with urology practices if they choose to
In the setting of suboptimal testos- neously twice yearly or every 6 months. administer this therapy to their patients.
terone suppression when using a lutein-
Sipuleucel-T Abiraterone and Enzalutamide
izing hormone-releasing hormone
(LHRH) agonist, it is also now common Sipuleucel-T is a novel immunotherapy Abiraterone is a 17-lyase and 17-hydro-
to switch a patient to degarelix to see if that is FDA approved for asymptomatic lase inhibitor, and blocks key pathways
it will decrease testosterone more effec- or minimally symptomatic M1 CRPC. in the steroid synthesis pathways lead-
tively. Sometimes a patient will not have This patient specific agent involves 3 ing to androgen production. Low dose
true CRPC because testosterone is not plasmapheresis procedures followed by prednisone (7.5 to 10 mg daily is a
completely suppressed with the LHRH sipuleucel-T administration a few days physiological dose) is recommended to
agonist, and switching to degarelix will later. The course of treatment is gener- be administered with abiraterone to help
more effectively suppress testosterone ally conducted during approximately limit overproduction of aldosterone, and
and delay the onset of CRPC. 4 weeks. This is an ideal treatment for the side effects of hypertension, hypoka-
urologists and staff to administer since lemia and fluid retention.
Denosumab patients are typically under the care The current FDA approved indica-
Denosumab is prescribed at a dose of urologists during this course of the tion for abiraterone is either before
of 120 mg (XGEVA), subcutaneous- disease and the treatment has few side or after the patient has experienced
ly, monthly, to prevent skeletal related effects. progression on docetaxel based sys-
events common in the later course of The ideal patient for sipuleucel-T will temic chemotherapy. For most patients
advanced metastatic prostate cancer. have documented clinical metastases and treated in 2014 the popular sequencing
Denosumab can be prescribed at the ini- will have an increasing PSA while on of novel agents would place the use of
tial diagnosis of bone metastatic prostate continuous hormonal therapy. He will abiraterone before systemic chemothera-
cancer or it can be withheld until the not have bone or cancer pain requiring py. The dose for abiraterone is 1,000 mg
patient experiences CRPC. In clinical narcotic pain medications. He must have orally given once daily along with a low
trials the patients all had CRPC, but a castrate testosterone level (less than 50 dose steroid (prednisone 5 mg orally,
the FDA approved a broadened indica- ng/dl) and meet the other on-label indi- twice daily).
tion requiring bony metastases but not cations. It is now estimated that more Enzalutamide is another novel oral
requiring the patient to have CRPC. than 99% of insured patients in the U.S. hormonal therapy agent that was FDA
Some clinicians believe we should will be covered for this treatment. Since approved in 2012 to treat men with
only use this agent in CRPC due to this is an active immunotherapy, ideally progression after docetaxel based che-
the cumulative risk of osteonecrosis of patients should be treated early in the motherapy. The drug is taken orally
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AUA 2014 ORLANDO, FL ANNUAL MEETING HIGHLIGHTS 11
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at a dose of 160 mg daily. Enzalu- FDA approved in the pre-chemother- ANSWER: Currently we do not
tamide is a novel oral antiandrogen that apy setting, although a 2013 company know. However, several large tri-
is more potent than prior generation press release reported a radiographic als should answer this question. The
agents such as flutamide, nilutamide and overall survival benefit, prompting PLATO trial is a phase 4, randomized
and bicalutamide. As of August 2014 the data safety monitoring committee to placebo controlled trial with 500 patients
it was only FDA approved in the post- recommend an un-blinding of trial par- planned comparing enzalutamide + abi-
chemotherapy clinical setting. However, ticipants with crossover to active drug in raterone + prednisone to abiraterone +
it also has activity in earlier stage disease the placebo arm. prednisone with progression-free sur-
and will likely soon be approved for use At the 2014 Genitourinary Cancers vival as the primary end point. In addi-
before chemotherapy. At that time it will Symposium the PREVAIL data were tion, the ALLIANCE trial will enroll
be more commonly prescribed by urolo- presented, showing a 2.2-month over- 1,224 chemotherapy nave patients to
gists. all survival benefit of enzalutamide vs enzalutamide alone vs enzalutamide +
Unlike abiraterone, enzalutamide placebo (32.4 vs 30.2 months) with a abiraterone + prednisone. The primary
does not have to be given with low dose median followup of 22.3 months and end point is overall survival with an esti-
prednisone. However, enzalutamide with 516 deaths (30% of the study popu- mated completion in 2019.
does have an approximate 1% risk of lation). This OS difference was statisti- 3. Once one drug is used, will there
seizures associated with its use. While cally significant.9 The table summarizes be a response to the other drug?
both novel oral hormonal agents are the drugs for CRPC and their overall ANSWER: We are starting to get
active in advanced prostate cancer, their survival benefit. some preliminary data that the response
benefit is not necessarily synergistic or There are many unanswered ques- to the second drug (whether abiraterone
cumulative. Patients will likely have an tions that we discussed during the or enzalutamide) is much shorter/less
initial robust response to either agent, course, primarily regarding the use and robust. PSA responses range from 8%
but switching to the other agent will like- sequencing of these novel oral hormonal to 45% and time to progression ranges
ly not result in a sustained response and agents. from 2.7 to 4.9 months.
the response to the second used agent 1. For early pre-chemotherapy meta- 4. In the era of health care reform and
may be more short-lived. Once both static CRPC how should the novel oral potentially fixed reimbursement for epi-
agents (abiraterone and enzalutamide) hormonal agents be sequenced? Putting sodes of care, how will these novel (and
are FDA approved in the pre-chemo- this another way, once enzalutamide expensive) therapies fare?
therapy CRPC setting, urologists will is (likely) FDA approved in the pre- ANSWER: This is a great question.
have an important sequencing choice in chemotherapy space, should we use We do not know, but worry about this
determining which of these 2 agents to abiraterone or enzalutamide first? as taxpayers and citizens. We remember
use first. ANSWER: The correct academic in 1989 when urologists were concerned
In the post-docetaxel setting the clini- answer is that we do not know. There about the then new concept of com-
cal and survival benefits of abiraterone are some patients who may be better bined hormonal therapy with flutamide
and enzalutamide are comparable, and suited for one vs the other. For example, and the $500 to $800 a month price
crossover resistance limits the efficacy of the diabetic patient may be better suited tag. Now we are in a whole new era of
each agent when the other is used first. for enzalutamide to avoid low dose costs. However, for our patients we are
In the pre-chemotherapy setting abi- steroids as opposed to the patient with also excited to have more effective treat-
raterone was FDA approved based on a seizure disorder who would be better ments to offer.
an approximate 8-month radiographic suited for abiraterone. It is unclear how 5. How will use of these new oral
progression-free survival benefit and a to use the overall survival difference (5.2 agents impact the use and efficacy of sys-
5.2-month increase in median OS (35.3 vs 2.2 months), if at all, to make initial temic chemotherapy such as docetaxel
months with abiraterone + prednisone treatment decisions. The PREVAIL trial and/or cabazitaxel?
vs 30.1 months with placebo + predni- had about 12% of patients with visceral ANSWER: Data from PREVAIL
sone). This translated to a 20% reduc- metastases vs none in COU-AA-302, show that chemotherapy can be delayed
tion in the risk of death (HR 0.792; 95% and PREVAIL occurred later, when from 10.8 months with placebo to 28
CI 0.655, 0.956; p=0.0151). more men received post-trial novel sur- months with enzalutamide (17.2 month
Interestingly this 5.2-month OS bene- vival enhancing agents. difference). In COU-AA-302 the delay
fit was not technically statistically signifi- 2. Are these 2 novel oral hormonal to chemotherapy in the prednisone +
cant based on the trial design of examin- agents synergistic? In other words, will placebo arm was 16.8 vs 26.5 months
ing the survival data multiple times.8 As we see a day when both are used with abiraterone + prednisone. Thus,
previously noted enzalutamide is not yet together? we know that chemotherapy will be
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12 AUA 2014 ORLANDO, FL ANNUAL MEETING HIGHLIGHTS
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delayed. However, it remains unclear 50 kBq (1.35 microcurie) per kg body 3. Cookson MS, Roth BJ, Dahm P et al: Castration-
resistant prostate cancer: AUA Guideline. J Urol
if chemotherapy will be less effective weight, given at 4-week intervals for 6 2013; 190: 429.
if used after the first line of novel oral injections. 4. Heidenreich A, Bastian PJ, Bellmunt J et al: EAU
guidelines on prostate cancer. Part II: Treatment
therapy. One concern is that urologists Urologists may be familiar with earli- of advanced, relapsing, and castration-resistant
may wait too long and miss a window of er generation radiopharmaceuticals such prostate cancer. Eur Urol 2014; 65: 467.
5. Moul JW and Dawson N: Quality of life associ-
opportunity for the effective use of che- as strontium but radium-223 is different. ated with treatment of castration-resistant prostate
motherapy. While we strongly believe It is alpha particle based and does not cancer: a review of the literature. Cancer Invest
that urologists can and should use the affect the bone marrow to the degree 2012; 30: 1.
6. Crawford ED, Shore ND, Moul JW et al: Long-
new agents, we also believe in a multi- of older agents. Thus, radium-223 is term tolerability and efficacy of degarelix: 5-year
disciplinary approach, and encourage much less likely to cause serious bone results from a phase III extension trial with a
1-arm crossover from leuprolide to degarelix.
urologists to work with oncologists to marrow toxicity with low white blood Urology 2014; 83: 1122.
avoid missed opportunities for optimal cell counts. In addition, the use of radi- 7. Schellhammer PF, Chodak G, Whitmore JB et al:
Lower baseline prostate-specific antigen is associ-
sequencing. um-223 was associated with an overall ated with a greater overall survival benefit from
survival benefit,10 whereas the older sipuleucel-T in the Immunotherapy for Prostate
Radium-223 radiopharmaceuticals were never prov- Adenocarcinoma Treatment (IMPACT) trial.
Urology 2013; 81: 1297.
The latest novel agent covered in the en to extend survival. Since radium-223 8. Rathkopf DE, Smith MR, de Bono JS et al: Updat-
has a unique mechanism of action, there ed interim efficacy analysis and long-term safety of
course was radium-223. This new agent abiraterone acetate in metastatic castration-resistant
is a parenteral radiopharmaceutical that might be a cumulative or synergistic prostate cancer patients without prior chemothera-
can be ordered by urologists and pro- effect when combined with other novel py (COU-AA-302). Eur Urol 2014; Epub ahead of
print.
vided in a nuclear medicine or radiation agents such as abiraterone or enzalu- 9. Beer TM, Armstrong AJ, Rathkopf DE et al:
oncology department setting. It is an tamide. However, this phenomenon has Enzalutamide in metastatic prostate cancer before
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and it received FDA approval in May ter radium-223 and survival in metastatic prostate
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PLENARY SESSIONS
ABSTRACT HIGHLIGHT
Introduction and Objectives Scott then performed bilateral adrenalec- However, in the last five years, seven
tomy and hypophysectomy to eliminate new agents have been developed includ-
The therapeutic landscape for the man-
adrenal androgen production. Larger ing degarelix, sipuleucel-T, denosumab,
agement of advanced prostate cancer
studies were then undertaken to bet- abiraterone, cabazitaxel, enzalutamide,
is rapidly evolving. In the last five
ter assess systemic ADT on prostate and radium-223. The optimal timing
years seven new treatments have been
cancer. The VA Cooperative Urologic and use in combination has yet to be
brought to market. Current controversy
Research Group found that treating discovered.
exists regarding the optimal therapy for
patients with DES was as effective as
patients with metastatic prostate cancer. Conclusions
orchiectomy; however, side effects lim-
A thorough understanding of the his-
ited its use. It wasnt until 40 years later We are now in the golden age of drug
tory and evolution of androgen depriva-
that the first tolerated medical systemic development for metastatic prostate can-
tion therapy is essential for Urologists
therapy, leuprolide acetate, was FDA cer. We challenge Urologists to learn
using these agents.
approved for castrate resistant pros- about the history of these medications
Methods tate cancer. This pivotal therapy was and how they have shaped the current
based on the Nobel Prize winning work treatment landscape. New studies are
The literature was reviewed for seminal of Andrew Schally, who discovered pushing the use of these therapies earlier
articles in androgen deprivation therapy the structure of gonadotropin releas- in the treatment algorithm. Understand-
for prostate cancer. ing hormone. From that time up until ing the path to our current environment
2008, five notable therapies have been lends perspective for the evolution and
Results
brought to market including flutamide, future of androgen deprivation therapy
In 1941, Charles Huggins discovered strontium, mitoxantrone, zolendronic for prostate cancer.
that eliminating testosterone through acid and docetaxel. Of these, only one
castration could delay advanced pros- modern chemotherapy agent (docetaxel)
tate cancer. Huggins along with W.W. demonstrates a clear survival benefit.
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