PARP Inhibitors For Newly-Diagnosed Patients
- PARP inhibitors for epithelial ovarian cancer work by interrupting the process of single stranded DNA repair, an essential part of cell replication. Defects in DNA repair ultimately cause cancer cell death.
- Some PARP inhibitors can be used in some newly-diagnosed ovarian cancer patients.
- The PARP inhibitor Zejula (niraparib) can be used for recently-diagnosed advanced ovarian cancer that has responded (complete or partial response) to platinum-based chemotherapy. The PARP inhibitor Lynparza (olaparib) is approved for women newly diagnosed with ovarian cancer and with a germline or somatic mutation in BRCA1/2.
How Do PARP Inhibitors Work?
The inhibitors operate by blocking the ability of cancer cells to repair damaged DNA, eventually leading to the death of these cells and helping patients toward remission. 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.
Read More 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.
Which Drugs Can Be Used for Newly-Diagnosed Ovarian Cancer?
- The PARP inhibitor Zejula (niraparib) has been approved by the FDA for all women with newly-diagnosed ovarian cancer regardless 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.
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