Education Only
This recap is for general education. It does not replace medical advice from a patient’s own cancer care team.
This webinar focused on men with high-risk prostate cancer and a clinical trial called EvoPAR-Prostate02. The discussion was led by Dr. Keith Crawford with guest expert Dr. Rana McKay, a genitourinary medical oncologist who treats prostate, kidney, bladder, and testicular cancers.
The goal was to help patients understand four main points:
- What high-risk prostate cancer means
- Why BRCA1 and BRCA2 testing may matter
- How PARP inhibitors may work
- What to ask before joining the EvoPAR-Prostate02 clinical trial
What does “high-risk prostate cancer” mean?
High-risk prostate cancer does not always mean the cancer has spread to distant parts of the body.
It means the cancer has features that make it more likely to come back or spread after treatment. Your care team may look at:
- Your PSA blood test result
- Your Gleason score or Grade Group from the biopsy
- Whether the cancer has grown outside the prostate
- Other biopsy or scan results that suggest the cancer may act more aggressively
Because high-risk cancer can be more likely to come back, treatment may involve more than one approach. This may include radiation therapy, hormone therapy, surgery for some patients, or a clinical trial.
Why BRCA testing matters?
Many people hear about BRCA1 and BRCA2 in breast or ovarian cancer. These genes can also matter in prostate cancer.
BRCA genes help repair damaged DNA. A harmful change in BRCA1 or BRCA2 can make DNA repair harder. This can raise cancer risk and may affect how some cancers behave.
Knowing whether a prostate cancer has a BRCA change may help patients and doctors talk about treatment options, clinical trials, and whether family members may need information.
A BRCA change can be found in two ways:
- Inherited, or germline: the person was born with the change. It is found in the body’s cells and may be passed to children. It may also matter for siblings and other relatives.
- Tumor-only, or somatic: the change is found only in the cancer cells. It is usually not passed down to children.
Men with high-risk prostate cancer should ask their care team whether they need tumor testing, inherited genetic testing, or both. A genetic counselor can help explain what the results may mean for the patient and family.
What is a PARP inhibitor?
PARP proteins help cells repair damaged DNA. A PARP inhibitor is a cancer drug designed to block this repair process.
Cancer cells with BRCA changes may already have trouble repairing DNA. Blocking PARP may make it even harder for those cancer cells to repair themselves. This may cause some cancer cells to die.
The drug discussed in this session is saruparib, also called AZD5305. Saruparib is investigational. This means it is still being studied and is not yet approved for this specific use.
Saruparib is designed to target PARP1. Researchers are studying whether this approach works well and what side effects it may cause.
What is EvoPAR-Prostate02?
EvoPAR-Prostate02 is a Phase 3 clinical trial. A Phase 3 trial is a large study that compares a new treatment approach with a standard approach.
This trial is studying men with BRCA1- or BRCA2-mutated high-risk or very high-risk prostate cancer. The main question is:
Main Research Question:
Can adding saruparib to usual treatment help men live longer without the cancer spreading?
The study plans to include about 700 men. Patients must meet detailed study rules to join.
In general, the study includes certain men with high-risk or very high-risk localized or locally advanced prostate cancer. It may also include some men who had prostate surgery and then had high-risk PSA recurrence and radiation treatment.
The main result being studied is called metastasis-free survival. This means how long a person is alive and the cancer has not spread to distant parts of the body.
What treatment do patients receive in the trial?
No one in this trial receives “no treatment.” Everyone receives the usual cancer treatment. The study is testing whether adding saruparib gives extra benefit.
Patients are assigned by chance to one of two groups:
- Usual treatment plus saruparib
- Usual treatment plus placebo
A placebo is a pill that looks like saruparib but does not contain the active study medicine.
Usual treatment includes radiation therapy and androgen deprivation therapy, also called ADT. Some very high-risk patients also receive abiraterone with prednisone or prednisolone.
Why is there a placebo?
The word “placebo” can make patients nervous. In this trial, the placebo does not replace usual cancer treatment. It only replaces the study drug.
This helps researchers compare the two groups fairly. If one group does better, researchers can better tell whether the difference was due to saruparib.
The study is also double-blind. This means neither the patient nor the doctor knows who is getting saruparib and who is getting placebo during the study. This helps reduce bias.
What is ADT?
ADT stands for androgen deprivation therapy. It is a common hormone treatment for prostate cancer.
ADT lowers testosterone or blocks testosterone signals. Prostate cancer often uses testosterone as fuel. Lowering or blocking testosterone can help slow prostate cancer growth.
ADT is often part of treatment for men with high-risk prostate cancer who receive radiation therapy.
What side effects were discussed?
Side effects can happen with the study drug and with usual hormone treatment. Every patient is different, so patients should ask the study team what side effects are most likely for them.
Possible side effects being watched for with saruparib may include:
- Tiredness
- Nausea or upset stomach
- Low red blood cells, also called anemia
- Low platelets, which can increase bruising or bleeding risk
- Low white blood cells, which can increase infection risk
Because of these risks, patients in the trial have regular blood tests.
- Hormone therapy may also cause side effects, such as:
- Hot flashes or night sweats
- Tiredness
- Sexual side effects, such as lower interest in sex or erection problems
- Mood changes
- Bone thinning
- Changes in energy, muscle strength, weight, or metabolism
Patients are not powerless in a clinical trial. They can ask questions, report side effects, ask whether treatment can be paused or adjusted, and choose to leave the trial.
What does participation involve?
Participation may involve:
- Taking tablets as directed
- Continuing ADT and, for some patients, abiraterone with prednisone or prednisolone
- Regular clinic visits
- PSA blood tests and other blood tests
- Imaging scans
- Blood count checks
- Side-effect monitoring
- Possibly using an electronic diary or medication diary
The visit schedule can vary. Patients should ask the study team exactly how often they would need to come in and how long each visit may take.
What about cost?
Study-specific items are often covered by the trial. These may include the study drug, some required tests, and tumor testing done only for the study.
Standard care items, such as routine PSA tests or scans, may be billed to insurance. Travel support can vary by study site. Patients should ask what costs are covered before joining.
Key message for patients
The main message from the session is that BRCA testing can matter for men with high-risk prostate cancer.
If a man has a BRCA1 or BRCA2 change, he may have treatment options or clinical trial options that are more targeted to his cancer biology. EvoPAR-Prostate02 may be one option to discuss with the care team.
This trial is not for every man with prostate cancer. It is focused on men with high-risk disease and a BRCA mutation who meet specific study rules.
Questions to ask your doctor or study team:
- Is my prostate cancer high-risk or very high-risk?
- Should I have BRCA1 and BRCA2 testing?
- Should I have inherited genetic testing, tumor testing, or both?
- If I have an inherited BRCA change, what could it mean for my family?
- Would radiation and ADT be part of my treatment plan?
- Am I eligible for a clinical trial?
- What are my treatment options if I do not join a trial?
- What are the possible benefits of joining?
- What are the risks and side effects?
- How often would I need visits, blood tests, and scans?
- What costs are covered by the trial?
- What happens if I want to stop participating?
Bottom line
This session explained why BRCA testing and PARP inhibitors are important areas of research in high-risk prostate cancer.
The EvoPAR-Prostate02 trial is studying whether adding saruparib, an investigational PARP1 inhibitor, to usual treatment can help men with BRCA-mutated high-risk prostate cancer live longer without the cancer spreading.
Patients should not make this decision alone. Men with high-risk prostate cancer should talk with their urologist, radiation oncologist, medical oncologist, and genetic counselor to understand whether testing or a clinical trial may be right for them.
Education Only
This recap is for general education. It does not replace medical advice from a patient’s own cancer care team.
Words to Know
Abiraterone
A hormone-blocking medicine used for some prostate cancers. It is usually taken with prednisone or prednisolone.
ADT
Androgen deprivation therapy. Treatment that lowers testosterone or blocks testosterone signals to help slow prostate cancer growth.
Biochemical recurrence
A rise in PSA after treatment, which may suggest the cancer has come back even if it cannot be seen on scans yet.
BRCA1 and BRCA2
Genes that help repair damaged DNA. Harmful changes in these genes can raise the risk of some cancers, including prostate cancer.
Double-blind
Neither the patient nor the doctor knows which group the patient is in during the study.
Germline change
An inherited gene change a person is born with. It may be passed from parent to child and may matter for blood relatives.
Harmful BRCA Change
A change in BRCA1 or BRCA2 that can affect cancer risk or treatment. A lab report may call this a pathogenic variant or likely pathogenic variant.
Localized prostate cancer
Cancer that is only in the prostate.
Locally advanced prostate cancer
Cancer that has grown outside the prostate area but has not spread to distant parts of the body.
Metastasis-free survival
The length of time a person is alive and the cancer has not spread to distant parts of the body.
PARP inhibitor
A drug that blocks PARP. In cancer treatment, this may keep cancer cells from repairing DNA damage.
PARP1
A protein that helps repair damaged DNA in cells.
Placebo
An inactive pill that looks like the study drug. In this trial, placebo does not mean no cancer treatment.
PSA
A blood test used to help detect or monitor prostate cancer. PSA can also rise for reasons other than cancer.
Randomized
Patients are assigned by chance to a treatment group.
Saruparib / AZD5305
An investigational tablet being studied in this trial. It is designed to block PARP1.
Somatic change
A gene change found only in the tumor cells. It is usually not inherited and usually not passed to children.