PARP Inhibitors and Bevacizumab for Maintenance
- For some women with ovarian cancer a new treatment option combing the PARP inhibitor olaparib (Lynparza) and a targeted therapy bevacizumab (Avastin) may be helpful and studies show this may be more effective than taking bevacizumab alone.
- Essentially this combination attempts to both starve cancer cells of oxygen using (bevacizumab) and keep the bad cancer cells from replicating (olaparib)
- Experts say ask your oncologists for genetic and molecular testing because the results are crucial to understanding treatment options.
- PARP inhibitors may now be offered to almost all women regardless of genetic make-up, though effectiveness can vary dramatically.
“Bevacizumab was the first drug approved by the FDA as a maintenance therapy for ovarian cancer,” says Dr. Heidi Gray, gynecologic oncologist at the Seattle Cancer Care Alliance.
Read MoreBevacizumab Plus PARP Inhibitors
The FDA has also approved another class of drugs, called PARP inhibitors, both for the primary treatment of ovarian cancer and in the maintenance setting. The PARP Inhibitor Lynparza is also approved in combination with (bevacizumab) for women with the right score on a test called HRD, which measures how well a cancer cell’s DNA replicates (see below). Some groundbreaking research has showed that combining these medications can provide very significant extension of what’s called progression free survival.PARP Inhibitors Explained
After initial surgery and chemotherapy, studies suggest that PARP inhibitors may help reduce the odds that a cancer will recur. These drugs attempt to block the body’s natural DNA repair mechanisms so cancerous cells are unable to divide and thrive. Studies suggest that using PARP inhibitors significantly extends the length of time until cancer recurs or worsens.
Your doctor will recommend the appropriate drug based on the genetics of your tumor and other details about your health and disease. Both of the approved drugs have been shown to be effective at prolonging the time until the cancer comes back.
“Originally, the focus was on PARP inhibitors among women who have BRCA1 or BRCA2 mutations because the PARP inhibitors work better in that population,” Dr. Gray says. But recent studies show there is still a benefit to using PARP inhibitors for almost every ovarian cancer patient, regardless of whether she carries a BRCA mutation.
Most recently, the American Society of Clinical Oncology (ASCO) released new guidelines recommending PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stage III or IV ovarian cancer and have improved with chemotherapy.
Common Side Effects of PARP Inhibitors
Unfortunately, like all cancer therapies, PARP inhibitors come with side effects. Whether or not you’ll experience significant side effects from PARP inhibitors depends on several factors, including which PARP inhibitor you’re taking, what dose you’re ingesting, and whether you’re using it alone or in combination with other therapies.
Still, the side effects of most PARP inhibitor protocols include:
- Nausea
- Vomiting
- Stomach upset
- Fatigue
These side effects can be intolerable for some patients, but in almost every case, doctors can offer options to alleviate or even eliminate them. A few possibilities:
- Discontinue treatment for a brief time period
- Reduce the dose
- Transition to another PARP inhibitor to see if there’s improvement
While most patients with ovarian cancer should have the option to try a PARP inhibitor, those who respond best tend to have high-grade disease, meaning the cancer is rapidly growing. Patients with low-grade disease may benefit from other categories of drugs, such as enzyme inhibitors or hormonal treatments.
No matter which category you fall into, it’s important to talk to your doctor about all available treatment options so you can make an informed decision. Ovarian cancer treatment is complex, but doctors have more tools at their disposal than ever before.
The Science Behind PARP Inhibitors
PARP inhibitors interrupt the process of single stranded DNA repair, an essential part of cell replication.
- Defects in DNA repair ultimately cause cell death. PARP inhibitors work best when there is a second error in DNA repair, such as that caused by a mutation in BRCA. BRCA is a critical player in homologous recombination, a highly effective double stranded DNA repair process. BRCA is not the only important part of homologous recombination, other genes are involved.
- The label homologous recombination deficient (HRD) indicates a tumor which has one of many possible errors in the double stranded DNA repair process of homologous recombination.
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