PARP inhibitors, rucaparib (Rubraca) and olaparib (Lynparza) receive FDA approval for metastatic prostate cancer

Expert Guidelines

The National Comprehensive Cancer Network has guidelines regarding which prostate cancer patients should undergo genetic counseling and testing. Men with the following factors should speak with a genetics expert about genetic testing:

• A tumor test result that suggests an inherited mutation (for example, a BRCA1, BRCA2 or ATM mutation in the tumor that may indicate an inherited mutation in one of those genes). 
• A blood relative who tested positive for an inherited mutation in a gene linked to prostate cancer.
• Metastatic prostate cancer diagnosed at any age.
• Intraductal/cribriform cells found by pathology.
• Cancer that is categorized as very high or high risk based on pathology.
• A diagnosis of male breast cancer.
• Eastern European (Ashkenazi) Jewish ancestry. 
• One or more first-, second- or third-degree relatives with breast cancer diagnosed at age 50 or younger, or ovarian, pancreatic, male breast cancer, metastatic prostate cancer or intraductal/cribriform prostate cancer at any age.
• Two or more close relatives diagnosed with breast or prostate cancer at any age.

The National Comprehensive Cancer Network (NCCN) recommends tumor testing to help guide treatment for people with metastatic prostate cancer.

• Testing for MSI-H/dMMR may help identify patients who would benefit from immunotherapy.  
• Testing for tumor mutations in HRR genes may help identify patients who would benefit from PARP inhibitors.
• Consider testing for a marker known as tumor mutational burden (TMB). People with a high tumor mutational burden (TMB-H) may benefit from immunotherapy. 

Questions To Ask Your Health Care Provider

• Am I eligible for treatment with a PARP inhibitor?
• Given my personal or family history, should I have genetic testing for an inherited mutation
• Should I have tumor biomarker testing?
• What are the risk and benefits of taking a PARP inhibitor?
• Will my insurance cover treatment with a PARP inhibitor?
• How much will my treatment cost? 

Open Clinical Trials

The following studies are looking at PARP inhibitors and similar agents for treating people with advanced prostate cancer.  

• NCT04592237: Chemotherapy, Immunotherapy and PARP Inhibitor for the Treatment of Metastatic Aggressive Variant Prostate Cancer. This study will look at how well the combination of chemotherapy drugs (such as cabazitaxel and carboplatin), a PARP inhibitors (niraparib), and an immunotherapy agents (cetrelimab) works for treating people with a rare type of prostate cancer known as aggressive variant prostate cancer (AVPC). 
• NCT04821622: TALAPRO-3: A Clinical Trial in Men with Metastatic Castration-Sensitive Prostate Cancer (mCSPC) and DNA Damage Repair (DDR) Gene Alterations. TALAPRO-3 is a trial for men who have been diagnosed with metastatic castration-sensitive prostate cancer (mCSPC) which means that the tumor has spread to other parts of the body but it is still sensitive to hormone therapies.  
• NCT05005728: XmAb®20717 Alone or in Combination With Chemotherapy or Targeted Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer. This study will look at the safety and clinical activity of the drug XmAb20717 alone or in combination with standard-of-care anticancer therapies in patients with metastatic castration-resistant prostate cancer who have been treated with at least 2 prior lines of treatment.
• NCT04455750: A Clinical Study Evaluating The Benefit of Adding Rucaparib to Enzalutamide for Men With Metastatic Prostate Cancer That Has Become Resistant To Testosterone-Deprivation Therapy. This trial is evaluating the benefit of rucaparib and enzalutamide combination therapy versus enzalutamide alone for the treatment of men with metastatic prostate cancer that has become resistant to testosterone-deprivation therapy.
• NCT03317392: Studying the Medication Olaparib Given with Radium-223 for Advanced Prostate Cancer with Bone Metastasis. This study is measuring the best dosage for and side effects of the drug combination olaparib and radium-223 to treat men with mCRPC that has spread to the bones. 
• NCT04497844: Treatment for Metastatic Castration-Sensitive Prostate Cancer and Inherited or Tumor Mutations in DNA Damage Repair Genes (Amplitude). The goal of AMPLITUDE is to see if adding niraparib to standard of care hormone therapy (ADT) is safe and more effective than standard of care alone. The study is enrolling people who have metastatic castration-sensitive prostate cancer and have an inherited or tumor mutation in one of the following genes involved in damage repair: BRCA1, BRCA2, BRIP1, CHEK2, FANCA,PALB2, RAD51B and RAD54L.

Other clinical trials for people with prostate cancer can be found here.

The following studies are looking at treatment for people with advanced solid tumors. 

• NCT05252390: NUV-868 Alone and in Combination With PARP Inhibitors in Patients With Advanced Solid Tumors.This study will test the safety and effectiveness of the experimental drug NUV-868 alone and combined with a PARP inhibitor in people with advanced solid tumors. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
• NCT05169437: PARP inhibitor (niraparib) in patients with inherited or tumor PALB2 mutations in advanced solid tumors (PAVO). PAVO is a Phase II study investigating if the PARP inhibitor niraparib is safe and effective for people with an advanced solid tumor who have an inherited PALB2 gene mutation or a tumor with a PALB2 mutation.
• NCT02264678: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents. This is a study of ceralasertib administered orally in combination with chemotherapy regimens and/or novel anticancer agents to patients with advanced cancer. The study is enrolling people with inherited mutations, including BRCA1, BRCA2, ATM, RAD51C, RAD51D, and people with tumors that are HRD-positive.  
• NCT04644068: Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (PETRA). This research is designed to learn whether treatment with a new PARP inhibitor, AZD5305, used alone or in combination with anti-cancer agents is safe, tolerable and has anti-cancer activity in patients with advanced solid tumors. The study is open to people who have previously been treated with PARP inhibitors.  
• NCT04267939: ATR Inhibitor Plus Niraparib Study in Advanced Solid Tumors and Ovarian Cancer. This study will look at how well people with advanced solid tumors respond to treatment with the targeted therapy BAY1895344 in combination with the PARP inhibitor niraparib. This study is open to people with inherited mutations in ATM, BRCA1, BRCA2 and other genes. Contact the study coordinator for information about eligibility for people with mutations in other genes. 
• NCT04657068: Treatment with ATR Inhibitor for Advanced or Metastatic Solid Tumors. This study will look at how well a new oral targeted therapy known as an ATR inhibitor works on advanced or metastatic solid tumors with mutations in genes that are linked to DNA damage repair. This study is open to people who have an inherited or acquired BRCA or ATM mutation or whose tumors are HRD-positive. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.