Chair, Matthew R. Smith, MD, PhD, Neeraj Agarwal, MD, and Tanya Dorff, MD, prepared useful Practice Aids pertaining to prostate cancer for this CME/MOC activity titled “Expanding Use of Hormonal Therapeutic Strategies in Prostate Cancer: Clinical Evidence and Practical Considerations for Individualized, Patient-Centered Care.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/3XfyDnA. CME/MOC credit will be available until March 17, 2024.

1. Patient-Centered Education:
Understanding Prostate Cancer Treatment Options
Full abbreviations, accreditation, and disclosure information available at PeerView.com/PNF40
Patient-centered education and support is key in prostate cancer care, as receiving
a cancer diagnosis can be overwhelming for patients and their caregivers.
The printable resource on the following page is designed to help patients and
their caregivers understand prostate cancer, navigate treatment options, and find
support through online groups and resources.
Printable Resource

2. Understanding Advanced Prostate Cancer:
A Quick Reference for Patients and Caregivers
If you or someone you love has been diagnosed with advanced prostate cancer,
you may have a lot of questions about treatment options and where you can turn for help.
What Are the Different Types of Advanced Prostate Cancer?
Non-metastatic castration-resistant prostate cancer (nmCRPC) is found only in the prostate and no
longer responds to hormonal therapy.
Metastatic castration-sensitive prostate cancer (mCSPC) has spread to the other parts of the body
such as bones, adrenal glands, liver, and lungs and still responds to testosterone-lowering treatments.
Metastatic castration-resistant prostate cancer (mCRPC) has spread to the other parts of the body,
including bones and lymph nodes, and no longer responds to testosterone-lowering treatments.
What Are the Different Treatment Options for Advanced Prostate Cancer?
Androgen deprivation therapy (ADT)
Hormonal therapy
PARP inhibition
Chemotherapy
Radiation
Radioligand
Combination therapies
What Is the Role of Genetic Testing in Prostate Cancer?
Genetic testing helps to identify who is at risk for prostate cancer or at risk for more aggressive
disease, and it aids in determining the most effective therapy options.
It is important to test family members if certain gene mutations are found in a patient with
prostate cancer.
Somatic and germline testing are recommended for all patients with metastatic prostate cancer
and some with locally advanced or high-risk localized prostate cancer.
Where Can You Get More Support?
Online and in-person advocacy foundations for patients and their caregivers provide
a variety of services, including support groups, information on treatments, genetic testing, clinical
trials, and educational workshops.
Visit the links below to learn more about the resources each organization offers.
Determining which treatment is right for you depends on your age
and what type of prostate cancer you have. Your cancer care team will help you make
a decision that takes into account your goals and preferences.
What Are the Different Side Effects Associated With
Prostate Cancer Treatments?
Hot flashes
Loss of libido/decreased sexual function
Fatigue
Hypertension
Loss of bone density
Falls and fractures
Fever/chills
Gastrointestinal effects
Cardiovascular/cardiometabolic effects
Anemia
Prostate cancer treatment can result in a number of side effects depending on the regimen chosen.
Talk to your doctor about how your treatment may affect your quality of life.
Spotlight on Clinical Trials
Your cancer care team may offer you the option of enrolling in a clinical trial. These studies provide
important information on whether a treatment is safe and effective and give you access to new
strategies that could be better than the options currently used.
Clinical trial enrollment is voluntary. Each trial has specific enrollment criteria, such as
age, type of cancer, stage, and prior treatments. Talk to your patient care team
about whether clinical trial enrollment is right for you.
ZERO - The End of Prostate Cancer
zerocancer.org/learn/resources
Online and Printable Information Guides
Peer-to-Peer Support
Online Support Communities
Webinars and Videos
Podcasts
Clinical Trial Information
Prostate Cancer Foundation
pcf.org/patient-resources
CANCERcare
cancercare.org/diagnosis/prostate_cancer
PCEC: Prostate Conditions Education Council
prostateconditions.org/

3. Hormonal Combination Approaches Under Study
in Advanced Prostate Cancer
Full abbreviations, accreditation, and disclosure information available at PeerView.com/PNF40
1. Wu C et al. Mol Cancer Ther. 2021;20:1680-1691. 2. Goel S et al. Trends Cell Biol. 2018;28:911-925. 3. Asim M et al. Nat Commun. 2017;8:374. 4. https://clinicaltrials.gov.
• Analogous to the estrogen receptor signaling
pathway in breast cancer, there is evidence that
the androgen receptor axis activates CDK4/6 to
sustain prostate cancer cell proliferation, and
upregulation of cyclin D1 is a potential mechanism
of resistance to next-generation hormonal therapy
– Inhibition of CDK4/6 may represent an
effective strategy to delay or overcome
primary androgen resistance in prostate cancer
• Abemaciclib, a selective and potent oral inhibitor
of CDK4/6 approved for certain breast cancers, has
been shown to induce cell cycle arrest and prostate
tumor growth inhibition in preclinical models
 Phase 3 CYCLONE 3 (NCT05288166):
abiraterone + prednisone ± abemaciclib in
high-risk mHSPC
 Phase 2/3 CYCLONE 2 (NCT03706365):
abiraterone + prednisone ± abemaciclib in mCRPC
 Phase 3 AMPLITUDE (NCT04497844):
abiraterone + prednisone ± niraparib in
HRR-mutated mHSPC
 Phase 3 TALAPRO-3 (NCT04821622):
enzalutamide ± talazoparib in DDR-mutated
mHSPC
 Phase 3 PROpel (NCT03732820): abiraterone +
prednisone ± olaparib in mCRPC
 Phase 3 MAGNITUDE (NCT03748641):
abiraterone + prednisone ± niraparib in mCRPC
 Phase 3 TALAPRO-2 (NCT03395197):
enzalutamide ± talazoparib in mCRPC
• Based on the high degree of HRR mutations in prostate cancer, the use of PARP inhibitors is effective.
Two PARP inhibitors are indicated as monotherapy in patients with mCRPC
– Olaparib is approved for HRR-mutated mCRPC based on the PROfound trial
– Rucaparib is approved for BRCA1/2-mutated mCRPC based on the TRITON2 trial
• Co-inhibition of AR and PARP promotes synthetic lethality with interdependency between both pathways and
enhanced activity, supporting the rationale for a co-targeting approach. There is a critical unmet need for
developing novel treatment options after resistance occurs with frontline next-generation hormonal agent
regimens, supporting the rationale for combining AR-targeting agents with PARP inhibition for the treatment
of patients with advanced prostate cancer
CDK4/6 Inhibition1,2
PARP Inhibition3
Selected Trials in Prostate Cancer4
Cyclin D
CDK4/6
inhibitors
G1
S
CDK4/6
Rb
P
E2F
T

4. Advanced Prostate Cancer: Bridging the Gap
Between Clinical Trials and Real-World Practice1-3
Full abbreviations, accreditation, and disclosure information available at PeerView.com/PNF40
1. Hotte SJ et al. Can Urol Assoc J. 2021;15:e90-e96. 2. Shayegan B et al. Urol Oncol. 2022;40:192.e1-192.e9. 3.clinicaltrials.gov.
Current Shortcomings in Real-World Management
• Given the potential to cure patients with localized disease,
effective treatment strategies are crucial to improving
long-term outcomes
• Many eligible patients are not receiving next-generation
androgen receptor (AR) inhibitors
• There are high rates of AE-related treatment discontinuations
with next-gen AR inhibitors
• Balancing treatment benefits and risks to optimize QOL
is often challenging
• Evidence on the use of next-generation anti-androgen
agents has broadened the scope of available and
effective treatments for patients with high-risk localized
and locally advanced prostate cancer
Neoadjuvant
• Phase 3 PROTEUS
• Phase 2 GUNS
• Phase 2 Neo-DAB
Adjuvant
• Phase 2 AASUR
• Phase 3 DASL-HiCaP
Role of Clinical Trials
High-Risk Localized/
Locally Advanced Prostate Cancer
Current Shortcomings in Real-World Management
Role of Clinical Trials
Advanced Prostate Cancer
• Androgen deprivation therapy (ADT) intensification—with docetaxel, hormonal
therapies, such as abiraterone acetate (AA) or AR inhibitors (eg, darolutamide,
apalutamide, or enzalutamide)—is underutilized in real-world practice
• Many patients still receive ADT monotherapy or first-generation anti-androgen
therapies
– Patients who do receive ADT + novel hormonal therapies are treated for shorter
durations compared with those treated in clinical trials
– Almost one-quarter of patients do not receive first-line therapy, and more than
half do not receive subsequent therapy
– Among patients who do receive therapy, novel hormonal therapies are underutilized
• Upfront intensified treatment with ADT + AR inhibitors ± docetaxel is now SOC for
mHSPC
• Overall HRQOL is maintained with treatment intensification
• Decisions regarding which therapy to combine with ADT for treatment intensification
should incorporate considerations of patient comorbidities and preferences
• Novel therapeutic strategies and combination approaches may lead to greater
therapeutic success
Triplet Therapy in mHSPC
• Phase 3 ARASENS
• Phase 3 PEACE-1
• Phase 3 ENZAMET
mHSPC
• Phase 3 AMPLITUDE
• Phase 3 TALAPRO-3
• Phase 3 CYCLONE-3
mCRPC
• Phase 3 MAGNITUDE
• Phase 3 PROpel
• Phase 3 TALAPRO-2
• Phase 2/3 CYCLONE-2
Additional Combination Strategies
Neoadjuvant/Adjuvant
• Phase 3 ENZARAD
• Phase 3 ATLAS