One of the biggest challenges with ovarian cancer is that most women are diagnosed late, after their cancer has already spread from their ovaries to other organs. The usual treatment for late-stage ovarian cancer is surgery plus chemotherapy, but the cancer often comes back a few months or years after these treatments.
A new group of targeted cancer drugs called PARP inhibitors are changing the way doctors treat ovarian cancer. These drugs are extending the time before the cancer comes back or gets worse, and they might even help some people with this cancer live longer.
PARP inhibitors work best against ovarian cancers that have certain genetic changes, but their use has expanded to also include cancers without gene changes. You might get one of these drugs if your cancer has come back after treatment, or soon after you're diagnosed.
How Do PARP Inhibitors Work?
PARP is short for poly-adenosine diphosphate-ribose polymerase. It's an enzyme – a type of protein – that helps your cells fix damaged DNA.
DNA is the double-stranded genetic material inside your cells. It holds the instructions that tell the cell how to work. Every time a cell divides, DNA makes copies of itself.
Cells constantly scan themselves for breaks in the DNA strands. When they detect a break, the cell fixes the damage so that it can keep growing and copying itself.
Cancer cells also use PARP to fix damage to their DNA. PARP inhibitors block this process. When cancer cells can't fix their damaged DNA, they can't multiply and they die.
Which Types of Ovarian Cancer Do PARP Inhibitors Treat?
PARP inhibitors were developed to work against ovarian cancers with homologous recombination deficiency (HRD). About half of ovarian cancers are HRD positive, which means they have a harder time repairing their DNA.
BRCA1 and BRCA2 gene changes are part of HRD. The BRCA genes help both cancer cells and normal cells fix themselves. People with BRCA gene mutations are at higher risk for ovarian, breast, prostate, and pancreatic cancers. BRCA genes already make it harder for cancer cells to fix themselves, which makes them easier for PARP inhibitors to target.
New evidence has shown that PARP inhibitors also work on ovarian cancers without BRCA mutations.
Three PARP inhibitors are approved to treat ovarian cancer with and without BRCA mutations:
When Would You Get This Treatment?
PARP inhibitors are for epithelial ovarian cancers, which make up about 90% of all ovarian cancers. These cancers start in the outer layer of the ovary.
You might get a PARP inhibitor if you have a BRCA gene mutation and:
- Your cancer got smaller after you took a platinum-based chemotherapy like cisplatin or carboplatin
- You already took two or more chemo drugs and they didn't shrink your cancer
- Your cancer came back after treatment, but then it responded to platinum-based chemotherapy
You can also get a PARP inhibitor if you don't have a BRCA gene mutation, but your cancer came back after treatment and then shrank from cisplatin or carboplatin chemotherapy.
Olaparib is sometimes combined with another targeted drug, bevacizumab (Avastin), as maintenance therapy in women with and without BRCA mutations. Maintenance therapy is an extra treatment to kill any cancer cells left behind after chemotherapy.
Niraparib can also be used as maintenance therapy in women with BRCA mutations who've responded to chemo. Usually you'll stay on maintenance treatment for 2 to 3 years.
PARP inhibitors are also approved for ovarian cancers without BRCA mutations that have a high genomic instability score. This test measures the number of abnormal genes in cancer cells.
Another PARP inhibitor, veliparib, is in clinical trials. Researchers are studying it as both a first treatment and a maintenance therapy.
How Do You Take PARP Inhibitors?
PARP inhibitors come as a pill or capsule that you take by mouth once or twice a day. How long you take them depends on your type of ovarian cancer.
Each PARP inhibitor works a little bit differently. Your doctor will fine-tune your dose and timing to help it work best against your cancer.
How Do They Help?
In women who are newly diagnosed with ovarian cancer and who have a BRCA mutation, PARP inhibitors can lower the risk of the cancer coming back by up to 70%. These medicines also work in some women who don't have a BRCA gene mutation.
In one study, Zejula increased the amount of time before the cancer got worse or came back by 6 months compared with an inactive treatment (placebo). Women with HRD tumors went 22 months without their cancer getting worse or coming back, compared with 10 months with a placebo.
Combining PARP inhibitors with other types of drugs might help them work even better. In women with HRD tumors, the combination of olaparib plus bevacizumab increased survival time without the cancer growing by 19 months compared with a placebo. The drug combo increased survival in women without HRD tumors by 5 months.
What Are the Possible Side Effects?
Everyone responds differently to cancer treatment. Most people do well on PARP inhibitors and don't have any serious problems. The most common side effects with these drugs are mild, like nausea, tiredness, and appetite loss.
Other common side effects are:
- Diarrhea or constipation
- Belly pain
Your doctor can give you advice on how to manage any side effects you have.
PARP inhibitors also lower the amount of cells in your blood, which may cause problems like:
- Anemia – low levels of red blood cells that carry oxygen around your body
- Thrombocytopenia – low levels of platelets that help your blood clot
- Neutropenia – low levels of white blood cells that fight infection
In about 1% of people who take PARP inhibitors, a cancer of the bone marrow and blood called myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) may develop. Your doctor will monitor you for MDS and AML once a week when you first start on treatment, and then once a month after that.
Should You Take a PARP Inhibitor?
If you have a BRCA gene mutation or other HRD, you're likely a good candidate for a PARP inhibitor. Some women without a DNA repair gene defect may also be able to take these medicines.
After you learn that you have ovarian cancer, your doctor will likely send you for genetic tests like these:
- Somatic testing looks for gene changes that happened during your lifetime
- Germline testing looks for gene changes you inherited from your parents
A technique called next-generation sequencing checks a sample of your DNA for the BRCA genes and other mutations.
The Future of PARP Inhibitors for Ovarian Cancer
Researchers are testing new PARP inhibitors to find ones that work against other kinds of ovarian cancer. They're also trying to get better at learning which people with ovarian cancer will benefit most from these drugs.
Studies are also looking at combining PARP inhibitors with different treatments to help it work better. One combination might include immune checkpoint inhibitors, which take the brakes off the immune system to help it find and kill cancer cells. With this combo treatment, PARP inhibitors would damage ovarian cancer cells, and then checkpoint inhibitors would send in immune cells to finish them off.