Early-stage prostate cancer is very treatable with surgery and radiation therapy. Once the cancer spreads, it becomes harder to stop. Late-stage prostate cancer treatments like chemotherapy and hormone therapy can eventually stop working.
PARP inhibitors are a new kind of prostate cancer treatment called a targeted therapy. The goal of targeted therapy is to kill cancer cells without harming healthy cells.
Unlike chemotherapy and hormone therapy, which kill cancer cells or stop them from growing, PARP inhibitors block an enzyme prostate cancer cells need to repair themselves. When damaged cancer cells can't fix themselves, they die.
PARP inhibitors can improve survival in men whose prostate cancer isn't responding to hormone therapy (called castration-resistant prostate cancer) and who have certain gene changes.
Before you have this treatment, it's important to understand what it does and how it might help you.
How Do PARP Inhibitors Work?
Every cell in your body contains a set of directions, called DNA, that tell them how to act, when to divide, and when to stop dividing. Changes, called mutations, in DNA cause cells to multiply when you don't need them. That's how cancer starts.
PARP, or poly-ADP ribose polymerase, is a protein found in each of your cells. Its job is to fix damaged DNA so that cells work like they should and don't multiply unless you need them.
Cancer cells also use PARP to repair themselves. PARP inhibitors block this protein to make it easier to kill cancer cells.
PARP Inhibitors for Prostate Cancer
PARP inhibitors work best on prostate cancers that have changes, or mutations, to genes that repair damaged DNA. About 1 in 4 men with late-stage, castration-resistant prostate cancer have these mutations.
Two of the most common gene mutations are BRCA1 and BRCA2. They make it harder for your cells to fix their damaged DNA.
The BRCA mutations both increase the risk for prostate cancer and help the cancer spread more quickly. Men with the BRCA2 gene are five times more likely to be diagnosed with prostate cancer than those without it.
BRCA gene mutations also help PARP inhibitors work better against prostate cancer. It's like adding gasoline to a smoldering fire. When you have the BRCA gene(s), PARP inhibitors speed up the cancer cell destruction process.
PARP inhibitors are available to treat breast cancer, ovarian cancer, and pancreatic cancer. Two PARP inhibitors are FDA-approved for prostate cancer: olaparib (Lynparza) and rucaparib (Rubraca). Others, like talazoparib (Talzenna) and niraparib (Zejula), are being studied in clinical trials.
How Do You Take Them?
Both olaparib and rucaparib come as pills that you take twice a day.
You'll take another medicine with the PARP inhibitor to block your body from making testosterone, a hormone that helps prostate cancer grow. You won't need hormone therapy if you already had bilateral orchiectomy surgery to remove both testicles.
How Well Do PARP Inhibitors Work?
In studies, PARP inhibitors helped men with prostate cancer live longer without their cancer growing.
A large study called PROFOUND compared PARP inhibitors to hormone therapy in men with late-stage, castration-resistant prostate cancer. Men who took olaparib lived twice as long without their cancer growing (7.4 months vs. 3.6 months) than those who took hormone therapy.
In a study of rucaparib, almost 45% of men with BRCA gene mutations saw their cancer improve on the drug. In more than half of men who improved on rucaparib, the response lasted for 6 months.
Studies are looking at whether adding chemotherapy or other drugs to PARP inhibitors might help them work even better.
Who Is a Good Candidate?
PARP inhibitors are approved for men with prostate cancer:
- Who have BRCA1, BRCA2, or another repair gene mutation
- Whose cancer has spread
- Whose cancer stopped responding to treatments like hormone therapy or chemotherapy
To find out whether you're a good candidate for a PARP inhibitor, your doctor can test for DNA changes in a sample of your blood or a piece of your tumor taken during a biopsy.
What Are the Side Effects?
The most common side effects from PARP inhibitors are:
- Low blood cell counts
- Tiredness
- Nausea and vomiting
- Appetite loss
- Diarrhea or constipation
Myelodysplastic syndrome (MDS) affects a small number of people who take PARP inhibitors. This group of cancers prevents early blood cells in bone marrow from maturing into the healthy adult blood cells your body needs to transport oxygen and fight infections.
Your doctor will closely monitor you for MDS and other side effects, and will treat you if they happen.
Talking to Your Doctor About PARP Inhibitors
Only about one-quarter of men with prostate cancer have the gene mutation that qualifies them to take a PARP inhibitor. New medicines that are now in clinical trials might one day expand the number of men who could benefit from this treatment.
If you have late-stage prostate cancer that isn't responding to chemotherapy or hormone therapy, you can ask your doctor about PARP inhibitors.
