Understanding PARP Inhibitors for Ovarian Cancer
- PARP inhibitors are drugs that work by preventing ovarian cancer cells from repairing damaged DNA and continuing to divide and spread once more.
- Data shows most women with ovarian cancer can benefit from PARP inhibitors at some point in the ovarian cancer journey, though they work better if a woman has the BRCA mutation.
- Timing options for PARP inhibitors include upfront maintenance, recurrence, and monotherapy.
Recent research has shown that women with ovarian cancer can benefit from PARP inhibitors at some point in their treatment, although the timing of that benefit can vary from patient to patient depending on a number of factors, including her cancer’s genetic profile.
Read More- Upfront maintenance: This means receiving PARP inhibitors directly after the first course of chemotherapy. This option is most effective for women whose ovarian cancer tumors have BRCA gene mutations.
- Recurrence setting: This option means PARP inhibitors are given after a woman has already had a complete or partial response to treatment in the past.
- Monotherapy: Down the line, PARP inhibitors can sometimes be option to use as treatment on their own, the technical term for which is “monotherapy”.
“But most of the time, patients tolerate PARP inhibitors fairly well,” Westwood says.
Overall, PARP inhibitors can have a really positive effect on progression-free survival, which means the amount of time that a woman with ovarian cancer can live without their cancer getting worse.
How PARP Inhibitors Work
One of the key things to know about PARP inhibitors is that your genetic makeup and specific features of your cancer will have a significant impact on how effective these drugs may be. Experts tell SurvivorNet that every woman with ovarian cancer should get a genetic test to determine if they have a mutation called BRCA, because the mutation enables PARP inhibitors to function much more powerfully. Importantly, there is increasing data that even women without BRCA mutations can still derive some benefit from these drugs.
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.
Newly-Diagnosed Epithelial Ovarian Cancer
The PARP inhibitor Zejula (niraparib) has been approved by the FDA for all women with newly-diagnosed ovarian cancer irrespective of whether the tumor is HRD. The drug is used after successful treatment with a platinum-based chemotherapy, the mainstay chemotherapy for ovarian cancer.
Due to limited benefit in progression free survival seen in the absence of HRD, gynecologic oncologists differ on whether PARP inhibitors should be universally recommended in the "upfront maintenance setting." Each patient should be made aware of risks and benefits to PARP inhibitor maintenance and decide with their oncologist what is the best treatment plan for them.
The PARP inhibitor Lynparza (olaparib) is approved for women newly-diagnosed with ovarian cancer and with a germline or somatic mutation in BRCA1/2.
Lynparza is also approved in combination with Avastin (bevacizumab) for women with HRD. Avastin is a blood vessel growth inhibitor, which works by starving the tumor of vital nutrients needed to grow.
Using PARPs To Treat Recurrence
Unfortunately, too often, ovarian cancer comes back.
For women with ovarian cancer who have had a recurrence and responded to platinum-based chemotherapy, Lynparza, Zejula and another PARP inhibitor called Rubraca (rucaparib) are FDA approved for use as a maintenance therapy, regardless of whether a woman has a BRCA mutation or HRD.
For some women who have had prior chemotherapy treatments, Rubraca, Zejula or Lynparza may also be options. These uses are based on factors such as number of prior therapies and BRCA mutation or HRD.
Important Guidelines
While PARP inhibitors are available to almost all women, women with BRCA gene mutations or who are HRD proficient may benefit the most from these drugs. However, 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.
Possible Side Effects
The different PARP inhibitors do have some varying side effects, which oncologists need to evaluate carefully. Some of these considerations are explained here.
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