Update: PARP inhibitors, rucaparib (Rubraca) and olaparib (Lynparza) receive FDA approval for metastatic prostate cancer
Video
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)
Summary
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)
Relevance
This article is most relevant for Men with metastatic castration-resistant prostate cancer who have certain inherited or tumor mutations in DNA repair genes
Relevance: High
Research Timeline: Post Approval
Media Ratings
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Who covered this study?
Medscape
First PARP inhibitor approved for metastatic prostate cancer
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Motley Fool
FDA approves new prostate cancer treatment from AstraZeneca and Merck
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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 olaparib (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.
Olaparib (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 enzalutamide (Xtandi) or abiraterone (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 olaparib 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.
This article is relevant for:
Men with metastatic castration-resistant prostate cancer who have certain inherited or tumor mutations in DNA repair genes
This article is also relevant for:
Metastatic cancer
People with a genetic mutation linked to cancer risk
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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.
Olaparib (Lynparza)
Approval of Lynparza was based on the PROfound clinical trial which showed:
- Progression-free survival was significantly longer for participants in the olaparib group (7.4 months) compared to the control group (3.6 months).
- Time to pain progression was significantly longer in the olaparib group than the control group.
- Overall survival was longer for patients in the olaparib 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 has guidelines on which men with cancer should undergo genetic counseling and testing. Men with the following should speak with a genetics expert about genetic testing:
- A tumor test result suggests an inherited mutation (for example, a , or 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 cancer.
- Metastic cancer diagnosed at any age.
- Intraductal/cribriform cells found on pathology.
- Cancer that is categorized as very-high- or high-risk based on pathology.
- Also diagnosed with male breast cancer.
- Eastern European (Ashkenazi) Jewish ancestry.
- One or more first-, second-, or third-degree relatives diagnosed with breast cancer at age 50 or younger, or ovarian, pancreatic, male breast cancer, cancer or intraductal/cribriform cancer at any age.
- two or more close relatives diagnosed with breast or cancer at any age.
Updated: 12/14/2021
Expert Guidelines
The National Comprehensive Cancer Network (NCCN) recommends tumor testing to help guide treatment in 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: 12/14/2021
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 inherited mutation
- 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 are looking at PARP inhibitors and similar agents for treating people with advanced cancer.
- NCT04592237: Chemotherapy, and for the Treatment of Aggressive Variant Cancer. This study will look at how well the combination of chemotherapy drugs (such as cabazitaxel and carboplatin), a PARP inhibitors (), and an agents (cetrelimab) works for treating people with a rare type of cancer known as aggressive variant cancer (AVPC).
- NCT04821622: TALAPRO-3: A Clinical Trial in Men with Castration-Sensitive Cancer (mCSPC) and Damage Repair (DDR) Gene Alterations. TALAPRO-3 is a trial for men who have been diagnosed with castration-sensitive 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 in Patients With Castration-Resistant 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 castration-resistant cancer who have been treated with at least 2 prior lines of treatment.
- NCT03012321: Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Castration-Resistant Cancer With Repair Defects. This phase II study in men with castration resistant cancer (mCRPC) is open to men with a or other mutation.
- NCT04455750: A Clinical Study Evaluating The Benefit of Adding to Enzalutamide for Men With Prostate Cancer That Has Become Resistant To Testosterone-Deprivation Therapy. This trial is evaluating the benefit of and enzalutamide combination therapy versus enzalutamide alone for the treatment of men with prostate cancer that has become resistant to testosterone-deprivation therapy.
Other clinical trials for people with cancer can be found here.
Updated: 08/06/2022
Open Clinical Trials
The following are studies looking at treatment for people with advanced .
- NCT05252390: NUV-868 Alone and in Combination With PARP Inhibitors in Patients With Advanced . This study will test how safe and effective the experimental drug NUV-868 is by itself and in combination with a in people with advanced . This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
- NCT05169437: () in patients with inherited or tumor mutations in advanced (PAVO). PAVO is a Phase II study investigating if the study drug, a called , is safe and effective for certain people who have been diagnosed with an advanced solid tumor with either an inherited or tumor 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 anti-cancer agents, to patients with advanced cancer. The study is enrolling people with inherited mutations including , , , , 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 if treatment with a new , AZD5305, 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 will look at how well 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 others. Contact the study coordinator for information about eligilibity for people with mutations in other genes.
- NCT04657068: Treatment with ATR Inhibitor for Advanced or Solid Tumors. This study will look at how well a new oral known as an ATR inhibitor works on advanced or with mutations in genes linked to damage repair. This study is open to people who have an inherited or acquired or mutation or people with tumors that are HRD-positive. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
Updated: 08/23/2022
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 your 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: 01/30/2022
Related Resources
The following resources focus on cancer.
- FORCE cancer resources:
- Information: cancer treatment
- XRAY reviews: cancer
- Video: What's New in Cancer Treatment?
- Video: Sexuality and Intimacy Issues for Men
- Video play list: cancer
- Blog category: cancer
- Malecare has extensive resources for people with cancer.
- National Comprehensive Cancer Network free patient guides:
Updated: 08/06/2022
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