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Study: PARP inhibitor treatment for metastatic prostate cancer shows most benefit in men with inherited BRCA mutations

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Contents

At a glance Questions for your doctor
Study findings Guidelines
Strengths and limitations Clinical trials
What does this mean for me? Related resources
In-depth Find support

 

STUDY AT A GLANCE

What is this study about?

This phase 2, study, called GALAHAD, looked at how well the niraparib works for treating people with castration-resistant cancer. The study enrolled people whose cancer returned or grew after multiple treatments. Participants who had an inherited or tumor mutation in or were compared to those who had an inherited or tumor mutation in an , , , FANCA, HDAC2 or gene. Of note, the group was mostly participants with a mutation. The study also looked at the safety of treatment with .

Why is this study important?

castration-resistant cancer (mCRPC) continues to grow despite treatment and carries a poor prognosis. Developing more effective treatments can help improve survival for people with mCRPC.

About one-fourth of mCRPC tumors have a mutation that affects the ability to repair certain types of damage.  Cancers with these mutations are said to have “ damage repair” gene defects (sometimes called DRD or DDR). Genes linked to damage repair include , , , and others. Cancer drugs known as PARP inhibitors were developed to treat tumors that have difficulty repairing damage due to mutations in these genes.

Two PARP inhibitors, (Lynparza) and (), are approved to treat mCRPC. , which was used in this study, is FDA-approved to treat people with certain types of ovarian, or primary peritoneal cancer, but is not yet approved for treating cancer.

Study findings

Participants were eligible if they had mCRPC and had received multiple treatments for mCRPC (hormone therapy or taxane chemotherapy or both).  Patients were excluded if they had been previously treated with a or platinum-based chemotherapy.

Eligible participants were grouped by mutation.

  • The group included participants who had:
    • an in or found through genetic testing (the majority of participants were included in this group and most had a mutation) or
    • a tumor mutation in or found through tumor testing.
    • Note: most participants in the group had a mutation in (89%, 127 of 131), only 4 had a mutation.
  • The non-BRCA group included participants who had:
    • an in , , , FANCA, HDAC2 or found through genetic testing or
    • a tumor mutation in , , , FANCA, HDAC2 or found through tumor testing. 

All participants received treatment with .

  • 34% of the group had a partial response (24 people) or complete response (2 people) to the treatment.
  • 11% of the non-BRCA cohort had a partial response (5 people) to treatment.  No one in the non-BRCA cohort had a complete response to treatment.
  • Adverse events were common but similar to what has been observed with therapy in other patient populations.
Group Total Partial response (%) Complete response (%)
76 24 (32%) 2 (3%)
Non-BRCA 47 5 (11%) 0 (0%)

 

In a virtual poster presented at the Oncology Nursing Society 2022 Congress, researchers reported on quality-of-life outcomes among GALAHAD participants. They evaluated the effect that had on overall health-related quality of life, including pain intensity and pain interference.  The results showed that improved or maintained these quality-of-life measures. This data can help inform health care providers while caring for patients receiving for advanced cancer.

Strengths and limitations

Strengths:

  • The GALAHAD study is a large multi-center Phase 2 study with participants from 15 countries. 
  • The participants were similar to each other in terms of their disease type and .  

Limitations:

  • 9% of patients (7 of 76) experienced disease progression before their first study evaluation and discontinued treatment.
  • 89% of the participants in the group had a mutation, so it is unclear whether those with mutations would respond similarly or not.

What does this mean for me?

If you have mCRPC, experts recommend genetic testing for inherited mutations (see our XRAY review on this topic here) and tumor testing to look for acquired mutations. Test results may change your treatment plan or make you eligible for a clinical trial. People who test positive for a or mutation through genetic testing or tumor testing may benefit from treatment with a .

 

References

Smith M, Scher H, Shahneen S, et al., in patients with castration-resistant cancer and repair gene defects (GALAHAD): a multicentre, , phase 2 trial. The Lancet Oncology 2022; 23(3):362-373. Published online February 4, 2022.

Tran M, Olivier K, Liu Y, et al. Effects of on health-related quality of life in the final analysis of the GALAHAD study in patients with castration-resistant cancer and repair gene alterations. Presented at the 47th Annual Oncology Nursing Society Congress; April 27-May 1, 2022; Anaheim, CA. Abstract P392.

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.

 

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posted 9/6/2022

This article is relevant for:

People with metastatic castration resistant prostate cancer who have an inherited or tumor mutation in BRCA2.

This article is also relevant for:

people with prostate cancer

people with castration-sensitive prostate cancer

people with a genetic mutation linked to cancer risk

people with metastatic or advanced cancer

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IN-DEPTH REVIEW OF RESEARCH

Study background

Researchers conducting the GALAHAD study wanted to know if the niraparib is an effective and safe treatment for people with castration-resistant cancer (mCRPC) and homologous repair deficiency. 

Populations looked at in this study

The GALAHAD study took place in 115 hospitals in 15 countries. The study began with 2,898 participants aged 64 to 74 years with castration-resistant (treatments that lower testosterone levels are no longer sufficient for disease control) cancer (mCRPC). Most participants (71%) were white.

All participants had prior cancer treatment, and their cancer continued to grow despitetreatment. Participants were excluded if they had previously been treated with a or platinum-based chemotherapy.

The participants were divided into two groups:

  • The cohort had germline or acquired mutations in or (most had a mutation).
  • The non-BRCA cohort had germline or acquired mutations in , , , FANCA, HDAC2 or . Within the two cohorts, participants were further divided as having measurable disease or non-measurable disease.

Most participants were white but a significant proportion (17%) were of unknown or unreported ethnicity.

Ethnicity Percent (n = 289)
White 71%
Asian 6%
Black 3%
Other 2%
Multiple 1%
Not reported 7%
Unknown 10%

 

Study design

GALAHAD was a phase 2 study exploring the potential effectiveness and safety of . The study had a single arm: All participants were prescribed 300 mg per day, which was given as oral capsules. In order to assess the effectiveness of , the response rate for measurable disease was assessed using CT scans to measure tumors at sites of disease. Safety was assessed by reporting adverse events that occurred between the date of the first dose of treatment and 30 days after the last dose of .

Study findings

Effectiveness of niraparib:

  • During treatment with , study visits occurred weekly for the first month, biweekly for the second month and monthly thereafter.
    • CT or and technetium bone scans were performed during visits every 8 weeks for 24 weeks and then every 12 weeks thereafter.
    • Circulating tumor cells were assessed every treatment cycle until cycle 7 and then at the end of treatment.
    • tests were done every 4 weeks until cycle 7 and then every three weeks after that.
  • In a subset of 76 men with or mutations and measurable disease, 26 (34.2%) had tumors that demonstrated response on CT scans to therapy. Of the 26 men whose tumors showed response to , 8 experienced tumor responses that were ongoing as of the most recent data collection.
  • Men in the cohort with non-measurable disease (as defined by the study protocol) responded to , based on blood tests and bone scan findings. 
  • Only 10.6% (5/47) of the non-BRCA cohort with measurable disease responded to .
  • Overall survival was longest for participants in the cohort with measurable disease.
  • Two patients in the measurable cohort achieved a complete response, compared to no patients achieving complete response in the non-BRCA cohort.

Safety of niraparib:

  • Adverse events were similar to those seen in patients who are treated with for other cancers.  
  • Nausea and anemia were the most common adverse events overall and were experienced by most participants (58% and 54%, respectively).
  • Other common adverse events included fatigue, vomiting, thrombocytopenia, constipation, decreased appetite, neutropenia and back pain.
  • Serious adverse events (grade 3 or higher) were experienced by two-thirds of patients. Most serious adverse events were hematologic: anemia, thrombocytopenia and neutropenia.
  • Two fatal adverse events may have been related to niraparib: urosepsis in the cohort and sepsis in the non-BRCA cohort.

Strengths and limitations

Strengths:

  • The GALAHAD study is a multi-center, multi-country study. 
  • All patients received the same treatment. All participants had been treated similarly prior to the beginning of this study.

Limitations:

  • 9% (7 of 76) of patients experienced disease progression before their first study evaluation and discontinued treatment.
  • About a quarter of participants had tumor mutations in , which are associated with an overall poor prognosis.
  • 89% of the participants in the group had a mutation, so it is unclear whether those with mutations would respond similarly or not.

Context

therapy with and has been FDA-approved for mCRPC in people with inherited and mutations. is a currently approved for ovarian cancer treatment. In the ovarian cancer setting, it is used to treat ovarian tumors with and without gene defects. Researching whether is potentially effective and safe for people with mCRPC who have inherited mutations or inherited or acquired mutations in other genes is consistent with the current knowledge about potential anti-tumor activity by PARP inhibitors.     

Conclusions

shows promise as a potential treatment for mCRPC, especially for people with inherited or acquired or mutations. Further study is needed to more fully determine the effectiveness of in the treatment of mCRPC tumors.

 

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posted 9/6/2022

Expert Guidelines
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 pathology report
  • 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
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
Questions To Ask Your Doctor

  • Is genetic testing recommended for me?
  • Does my cancer have ()?
  • Is my cancer ?
  • Is therapy appropriate for me?

Open Clinical Trials
Open Clinical Trials

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

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

Updated: 11/09/2023

Peer Support
Peer Support

The following organizations offer peer support services for people with or at high risk for cancer:

Updated: 03/08/2023

Who covered this study?

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