PARP Inhibitors

PARP inhibitors are a class of medicines used in select patients with advanced prostate cancer. Patients are eligible for therapy if they have mutations in certain genes involved in DNA repair. These “DNA damage repair” (DDR) genes include the prostate, breast, and ovarian cancer risk genes BRCA1 and BRCA2, as well as others. PARP inhibitors currently FDA-approved for metastatic castration-resistant prostate cancer (mCRPC) are: olaparib (Lynparza®), rucaparib (Rubraca®), talazoparib (Talzenna®; in combination with enzalutamide) and niraparib (in combination with abiraterone as Akeega®).

There are some differences in the use of each drug, such as the specific gene mutations used to select patients, how they may be combined with androgen receptor pathway inhibitors, and the timing of when they can be administered in the course of mCRPC. Potentially serious side effects include bone marrow problems, lung inflammation (pneumonitis), and blood clots.

Testing of mCRPC patients to identify those who have DDR mutations and may benefit from PARP inhibitors is now becoming increasingly available. This testing can be done on blood and/or tumor tissue.

A sizable proportion of patients with metastatic prostate cancer have these mutations and thus may be candidates for treatment with PARP inhibitors: Up to 25%–30% have these mutations (inherited or acquired) in their tumor tissue, and about 12% have inherited DDR mutations in the DNA they got from their parents. Cancer cells that already have mutations in BRCA1, BRCA2, or other DDR genes will instead rely on the repair protein called PARP. Blocking PARP with a medication makes the cancer cells unable to repair themselves, and results in cancer cell death. In practice, not all patients will respond to these medications, and response may be linked to the specific type of DDR mutation.

Patients with metastatic prostate cancer should strongly consider genetic counseling and genetic testing for inherited mutations. The results of testing can inform whether you may benefit from treatment with PARP inhibitor medicines. Testing may also show whether you carry a genetic mutation that could increase family members’ risk for prostate or other cancers. This information can help you and your family create a plan for cancer prevention and earlier detection.

If you have a family history of prostate, breast, ovarian, pancreatic or other cancers, it is important to talk to your doctor about genetic counseling and testing, for you and family members.

Last Reviewed: 12/2023