Update: PARP inhibitors, rucaparib (Rubraca) and olaparib (Lynparza) receive FDA approval 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 and references
Guidelines  


APPROVALS AT A GLANCE

The FDA approved use of the PARP inhibitors rucaparib (Rubraca) and olaparib (Lynparza) for treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have certain inherited or tumor mutations.

Why are these FDA approvals important? 

These mark the first FDA approvals of PARP inhibitors to treat prostate cancer. Until now, treatment options for men with mCRPC have been limited to hormone therapy, radiation, chemotherapy, and immunotherapy. The addition of PARP inhibitors offers a new treatment option for some men with mCRPC.

PARP inhibitors have already been approved to treat metastatic breast cancer, pancreatic cancer and advanced ovarian cancer. 

What do the FDA approvals say? 

Rucaparib (Rubraca)

The FDA granted approval of Rubraca for treatment of men with mCRPC who have one of the following mutations:

  • an inherited BRCA1 or BRCA2 mutation 
  • an acquired BRCA1 or BRCA2 mutation in their tumor

Men are eligible for Rubraca if they have already been treated with androgen deprivation (hormone therapy) and a taxane-based chemotherapy. 

Olaparib (Lynparza)

The FDA granted approval of Lynparza for treatment of men with mCRPC who have either: 

  • an inherited BRCA1 or BRCA2 mutation
  • an acquired mutation in their tumor in any of the following genes associated with a type of DNA repair called "homologous recombination repair" (HRR):
    • ATM, BRCA1, BRCA2, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, 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 PARP inhibitor if you have an inherited BRCA mutation, or a mutation in a gene involved in homologous recombination repair (HRR) found with tumor biomarker testing. 

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Posted 6/1/20

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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Questions to Ask
  • 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? 
Clinical Trials
  • NCT03338790: A Phase 2 Study of Nivolumab in Combination with Either Rucaparib, Docetaxel, or Enzalutamide in Men with Castration-resistant Metastatic Prostate Cancer (CheckMate-9KD). The purpose of this study is to compare three different combination therapies, each containing a drug called nivolumab and another anti-cancer drug in men metastatic prostate cancer. 
  • NCT02975934: A Study of Rucaparib Verses Physician's Choice of Therapy in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (TRITON3). TRITON3 study is looking at how well the PARP inhibitor rucaparib (Rubraca) works for men with certain DNA damage repair mutations and advanced prostate cancer.
  • NCT03012321: Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects. This is a phase II study in men with metastatic castration resistant prostate cancer (mCRPC) open to men with certain mutations linked to DNA damage repair.
  • NCT03442556: Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency. This trial studies how well docetaxel with carboplatin followed by rucaparib camsylate works in treating patients with metastatic castration resistant prostate cancer. The study is open to men with certain mutations linked to DNA damage repair. 
  • NCT02203513: A Phase II Single Arm Pilot Study of the Chk1/2 Inhibitor (LY2606368) in BRCA1/2 Mutation Associated Breast or Ovarian Cancer, Triple Negative Breast Cancer, High Grade Serous Ovarian Cancer, and Metastatic Castrate-Resistant Prostate Cancer. The goal of this study is to see if LY2606368 helps shrink tumors in patients with certain breast, ovarian or prostate cancers.
  • NCT04030559: Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects. This trial studies how well niraparib, when given before surgery, works in treating patients with high risk prostate cancer that has not spread to other parts of the body.

IN-DEPTH REVIEW OF RESEARCH RELATED TO APPROVALS

Rucaparib (Rubraca)

Approval of Rubraca was based on preliminary results from the ongoing (not recruiting) TRITON2 clinical trial.

  • Among the patients with a BRCA 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 PSA response (great than 50% decrease in PSA levels) with a median duration of PSA response of 5.5 months.
  • Among patients with an ATM, CHEK2 or CDK12 mutation both  overall response and PSA response were poor. Overall response for was:
    • 9% for patients with an ATM mutation
    • 0% for patients with a CHEK2 or CDK12 mutation.

​PSA response was:

  • 3.5% for patients with an ATM mutation
  • 7.1% for patients with a CDK12 mutation
  • 14.3% for CHEK2

The most common side effects of Rubraca included:

  • Fatigue
  • Nausea
  • Anemia
  • Decreased appetite
  • Constipation
  • Rash
  • Vomiting
  • Diarrhea
  • Increased liver enzymes

Rubraca has already received FDA 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 FDA approval for treatment of select patients with advanced ovarian, pancreatic and breast cancer. 

 

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