For those with advanced ovarian cancer, the first-line treatment is typically a combination of surgery and platinum-based chemotherapy. To help delay relapse, maintenance therapies are often recommended next to help control cancer and minimize disease progression. One category of maintenance treatment options works by targeting and blocking poly adenosine diphosphate-ribose polymerase (PARP), which helps repair damaged DNA.
PARP inhibitors have been studied extensively and are a safe and effective way to control ovarian cancer. Learning more about how these drugs work and what to expect when taking them can help you have a better conversation with your doctor about treatment options.
Researchers first discovered the role of PARP in ovarian cancer in 1963. PARP is a protein that plays a role in repairing damaged DNA. It works along with several other proteins, including BRCA1 and BRCA2, to help fix broken DNA. For several years, ovarian cancer has been diagnosed and treated based on BRCA mutation status.
The first PARP inhibitor was discovered in 1980. Since then, several more have been developed and approved by the U.S. Food and Drug Administration (FDA). Initially, these therapies were studied to be used alongside chemotherapy and radiation therapy. However, they are now known to work effectively on their own to block PARP proteins.
Targeting PARP has provided a new way to treat advanced epithelial ovarian cancers and high-grade serous ovarian cancers (HGSOC) that have shrunk after first-line treatments. Used this way, it’s known as maintenance therapy because it can help delay or prevent cancer from coming back.
When the DNA repair process is faulty, the DNA in cells can’t repair itself properly, leading to the development of mutations. These mutations can then give rise to cancer. In fact, almost 50 percent of women who have HGSOC have tumors with mutations caused by this type of defect.
In women with BRCA mutations, blocking PARP proteins makes it difficult for BRCA proteins to repair damaged DNA. As a result, these damaged cells die. Having a mutation in the BRCA1 gene makes cells extremely sensitive to PARP inhibitors, making them a highly effective treatment for ovarian cancer.
Read more about how maintenance treatments for ovarian cancer work.
There are currently three FDA-approved PARP inhibitors available:
Each can be given to women with or without BRCA gene mutations.
Niraparib can be used as first-line maintenance therapy in women with or without a mutation in a BRCA gene who were treated with platinum-based chemotherapy to shrink their tumors. Rucaparib can also be used to treat platinum-sensitive tumors that have shrunk in response to chemotherapy in women with or without a BRCA gene mutation.
Olaparib can be used on its own (this is called monotherapy), or together with bevacizumab. Bevacizumab (sold under the brand name Avastin) is a different kind of treatment known as an angiogenesis inhibitor. It works by preventing the growth of new blood vessels in tumors, cutting off their supply of oxygen and nutrients. Together, olaparib plus bevacizumab are used as maintenance therapy for tumors that have shrunk with platinum-based chemotherapy in women with BRCA gene mutations.
Another PARP inhibitor, veliparib, is currently being studied in clinical trials.
Niraparib is taken by mouth once daily. Rucaparib and olaparib are taken by mouth twice daily. Each can be taken with or without food. If your doctor prescribes bevacizumab in combination with olaparib, it’s given by intravenous (IV) infusion every two to three weeks.
The length of time that PARP inhibitors are taken can vary depending on your oncologist’s recommendations. Because these medications have only been available for a few years, there aren’t guidelines established for long-term use.
Doctors often look at what happened in clinical trials when prescribing newer drugs. In the PRIMA trial investigating niraparib, treatment was given for up to three years or until cancer progressed. In the PAOLA-1 trial that studied the combination of olaparib plus bevacizumab, participants were treated for up to 24 months or until cancer progressed.
Given these facts, it’s reasonable to expect that PARP inhibitors may be prescribed for two to three years, or until cancer progresses. Ask your doctor what you can expect based on the details of your condition.
Learn more about what to expect from maintenance treatment for advanced ovarian cancer.
Throughout their respective clinical trials, niraparib, rucaparib, and olaparib were proven to be safe and effective as maintenance therapies for treating advanced ovarian cancer. However, all medications (even those available over the counter) can cause side effects. In clinical trials, these are known as adverse events.
General side effects that have been reported with PARP inhibitors as a category include:
The most commonly reported side effects of niraparib during studies included changes in blood cell counts, including anemia (low red blood cell counts). In the phase 3 clinical trial studying rucaparib, women mainly reported nausea, headache, and anemia.
Similar to other PARP inhibitors, olaparib’s most common side effects included anemia. Overall, the medication was well tolerated by participants, and only 12 percent of them left the trial because of side effects.
In a study on olaparib, three participants (1 percent) developed a type of blood cancer known as acute myeloid leukemia (AML) after stopping treatment with olaparib. For this reason, the FDA recommends blood tests to regularly monitor blood cell counts in women receiving olaparib for early signs of AML or myelodysplastic syndrome, another type of blood cancer.
One of the most important parts of a maintenance treatment plan is sticking with it. Taking your medication daily or as directed by your doctor ensures that it is working as effectively as possible to give you the best chance of avoiding relapse. If you are struggling with sticking to your treatment — whether it is due to side effects, cost, or another factor — let your doctor know.
Being open and communicating your experiences with your doctor can let them know what’s working for you and what’s not. From there, they can make suggestions for managing side effects, or potentially switch your medication if necessary.
Learn more about ways to manage the side effects of advanced ovarian cancer treatment.
On MyOvarianCancerTeam, the social network for people with ovarian cancer and their loved ones, more than 4,800 members come together to ask questions, give advice, and share their stories with others who understand life with ovarian cancer.
Are you taking a PARP inhibitor for maintenance treatment? Share your experiences in the comments below, or start a conversation by posting on MyOvarianCancerTeam.