Update: PARP inhibitors, rucaparib (Rubraca) and olaparib (Lynparza) receive FDA approval for metastatic prostate cancer
The FDA approved two PARP inhibitors, rucaparib (Rubraca) and olaparib (Lynparza) for treatment of metastatic castration-resistant prostate cancer (mCRPC) in men who have certain inherited mutations or tumor mutations. (6/1/20)
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The FDA approved two PARP inhibitors, rucaparib (Rubraca) and olaparib (Lynparza) for treatment of metastatic castration-resistant prostate cancer (mCRPC) in men who have certain inherited mutations or tumor mutations. (6/1/20)
Most relevant for: Men with metastatic castration-resistant prostate cancer who have certain inherited or tumor mutations in DNA repair genes.
It may also be relevant for:
- people with metastatic or advanced cancer
- people with a genetic mutation linked to cancer risk
Relevance: High
Research Timeline: Post Approval
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First PARP inhibitor approved for metastatic prostate cancer
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Contents
| At a glance | Questions for your doctor |
| What does this mean for me? | In-depth |
| Clinical trials | Resources |
| Guidelines |
APPROVALS AT A GLANCE
The approved use of the PARP inhibitors () and (Lynparza) for treatment of men with castration-resistant cancer (mCRPC) who have certain inherited or tumor mutations.
Why are these approvals important?
These mark the first approvals of PARP inhibitors to treat cancer. Until now, treatment options for men with mCRPC have been limited to hormone therapy, radiation, chemotherapy, and . The addition of PARP inhibitors offers a new treatment option for some men with mCRPC.
PARP inhibitors have already been approved to treat breast cancer, pancreatic cancer and advanced ovarian cancer.
What do the approvals say?
()
The granted approval of for treatment of men with mCRPC who have one of the following mutations:
- an inherited or mutation
- an acquired or mutation in their tumor
Men are eligible for if they have already been treated with androgen deprivation (hormone therapy) and a taxane-based chemotherapy.
(Lynparza)
The granted approval of Lynparza for treatment of men with mCRPC who have either:
- an inherited or mutation
- an acquired mutation in their tumor in any of the following genes associated with a type of repair called " repair" (HRR):
- , , , , , CDK12, CHEK1, , FANCL, , RAD51B, , , RAD54L
Men with mCRPC are eligible for Lynparza if their cancer has progressed following treatment with (Xtandi) or (Zytiga).
What does this mean for me?
If you have mCRPC and you have already received hormone therapy and chemotherapy, you may benefit from treatment with a if you have an inherited mutation, or a mutation in a gene involved in repair (HRR) found with tumor testing.
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Posted 6/1/20
References
grants accelerated approval to for BRCA-mutated castration-resistant cancer. website, May, 2020.
approves for HRR gene-mutated castration-resistant cancer. website, May 2020.
Disclosure
FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
IN-DEPTH REVIEW OF RESEARCH RELATED TO APPROVALS
()
Approval of was based on preliminary results from the ongoing (not recruiting) TRITON2 clinical trial.
- Among the patients with a mutation:
- 43.9% had a confirmed overall response rate (percentage of patients whose cancer shrinks or disappears) most of which lasted more than 24 weeks.
- 52.0% had a confirmed response (great than 50% decrease in levels) with a median duration of response of 5.5 months.
- Among patients with an , or CDK12 mutation both overall response and response were poor. Overall response for was:
- 9% for patients with an mutation
- 0% for patients with a or CDK12 mutation.
PSA response was:
- 3.5% for patients with an mutation
- 7.1% for patients with a CDK12 mutation
- 14.3% for
The most common side effects of included:
- Fatigue
- Nausea
- Anemia
- Decreased appetite
- Constipation
- Rash
- Vomiting
- Diarrhea
- Increased liver enzymes
has already received approval for treatment of select patients with advanced ovarian cancer.
(Lynparza)
Approval of Lynparza was based on the PROfound clinical trial which showed:
- Progression-free survival was significantly longer for participants in the group (7.4 months) compared to the control group (3.6 months).
- Time to pain progression was significantly longer in the group than the control group.
- Overall survival was longer for patients in the group (18.5 months) compared to the control group (15.1 months), although at the time the analysis was done, this difference was not statistically significant.
The most common side effects of Lynparza included:
- Anemia
- Nausea
- Fatigue
- Decreased appetite
- Diarrhea
- Vomiting
- Thrombocytopenia (low blood platelets or white blood cells)
- Cough
- Dyspnea or shortness of breadh
Lynparza has already received approval for treatment of select patients with advanced ovarian, pancreatic and breast cancer.
Expert Guidelines
The National Comprehensive Cancer Network guidelines recommend genetic counseling and testing for the following people with cancer who have:
- a tumor test result that suggests an inherited mutation
- for example, a tumor with a , or mutation may indicate an in one of those genes
- a blood relative who tested positive for an in a gene linked to cancer
- cancer diagnosed at any age
- cancer that has spread to the
- localized cancer (hasn’t spread beyond the ) that is considered very high-risk or high-risk
- intermediate-risk cancer with intraductal or cribriform features listed on the
- a diagnosis of male breast cancer
- Eastern European (Ashkenazi) Jewish ancestry
- one or more relatives with:
- breast, colorectal or endometrial cancer diagnosed at age 50 or younger
- male breast cancer, triple negative breast cancer, ovarian cancer or pancreatic cancer at any age
- , regional, very-high-risk, or high-risk cancer at any age
- one or more close relatives with cancer diagnosed at age 60 or younger
- three or more relatives on the same side of the family with biliary tract, breast, colorectal, endometrial, glioblastoma, or other cancers
Speak with a genetic counselor if you have questions about whether you meet guidelines for genetic testing.
Updated: 02/01/2024
Expert Guidelines
The National Comprehensive Cancer Network (NCCN) recommends tumor testing to help guide treatment for people with prostate cancer.
- Testing for MSI-H/dMMR may help identify patients who would benefit from .
- Testing for tumor mutations in HRR genes may help identify patients who would benefit from PARP inhibitors.
- Consider testing for a marker known as (TMB). People with a high (TMB-H) may benefit from .
Updated: 03/01/2023
Questions To Ask Your Doctor
- Am I eligible for treatment with a ?
- Given my personal or family history, should I have genetic testing for an
- Should I have tumor testing?
- What are the risk and benefits of taking a ?
- Will my insurance cover treatment with a ?
- How much will my treatment cost?
Open Clinical Trials
The following studies look at PARP inhibitors and similar agents for treating people with advanced cancer:
- NCT05932862: Study of a New InvestigationaI Inhibitor to Treat People with Advanced . The study examines the safety and effectiveness of the investigational treatment XL309 when used alone or in combination with a to treat people with some advanced , including cancer.
- NCT05005728: XmAb®20717 Alone or in Combination With Chemotherapy or in Patients With Castration-Resistant Cancer. This study looks at the safety and clinical activity of the drug XmAb20717 alone or in combination with standard-of-care anticancer therapies in patients with castration-resistant cancer who have been treated with at least 2 prior lines of treatment.
- NCT05417594: Study of the AZD9574 Alone and Combined with Other Cancer Medicines to Treat People with Advanced Solid Cancers (CERTIS1 Study). This study looks at a new AZD9574 given alone and in combination with other anti-cancer drugs for people with advanced cancer that has come back or progressed.
Other clinical trials for people with cancer can be found here.
Updated: 11/03/2024
Open Clinical Trials
The following studies look at treatment for people with advanced .
- NCT02264678: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents. This is a study of orally administered ceralasertib combined with chemotherapy regimens and/or novel anticancer agents for patients with advanced cancer. The study enrolls people with tumors that are HRD-positive or who have inherited mutations in , , , or .
- 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 , AZD5305, used alone or in combination with anti-cancer agents is safe, tolerable and has anti-cancer activity in patients with advanced . The study is open to people who have previously been treated with PARP inhibitors.
- NCT04267939: ATR Inhibitor Plus Study in Advanced and Ovarian Cancer. This study looks at how well people with advanced respond to treatment with the BAY1895344 in combination with the . This study is open to people with inherited mutations in , , 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 Solid Tumors. This study looks at how well a new oral known as an ATR inhibitor works on advanced or with mutations in genes that are linked to damage repair. This study is open to people who have an inherited or acquired or mutation or whose tumors are HRD-positive. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
Updated: 03/28/2025
Peer Support
The following organizations offer peer support services for people with or at high risk for cancer:
- FORCE peer support
- Visit our message boards.
- Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Sign up for our Peer Navigation Program.
- Users are matched with a volunteer who shares their mutation and situation.
- Join our private Facebook group.
- Find a virtual or in-person support meeting.
- Join a Zoom community group meeting.
- Visit our message boards.
- ZERO-The End of Cancer is a nonprofit organization that provides information and support resources for men with cancer.
Updated: 03/08/2023
Related Resources
The following resources focus on cancer.
- FORCE cancer resources:
- Advocacy groups:
- National Comprehensive Cancer Network free patient guides:
Updated: 01/30/2025
Who covered this study?
Medscape
First PARP inhibitor approved for metastatic prostate cancer
This article rates 4.0 out of
5 stars
Motley Fool
FDA approves new prostate cancer treatment from AstraZeneca and Merck
This article rates 3.0 out of
5 stars