New option for first treatment of metastatic prostate cancer

RELEVANCE

Most relevant for: People with metastatic castration resistant prostate cancer who have an inherited or tumor mutation in certain genes..

It may also be relevant for:

people with prostate cancer
people with castration-resistant prostate cancer
people with a genetic mutation linked to cancer risk
people with a family history of cancer

Relevance: Medium-High

Research Timeline: Post Approval

Relevance rating details

What is this update about?

The (Food and Drug Administration) approved together with Xtandi as a treatment for people with castration-resistant cancer (mCRPC). This approval is for people who have an or tumor mutation in the following genes: , , , ATR, CDK12, , FANCA, MLH1*, MRE11A, , or . Talzenna is given with Xtandi, which is already used to treat metastatic prostate cancer.

*Although mutations are included in the approval, MLH1 works differently to repair damage than the other listed genes.

Why is this update important?

Metastatic prostate cancer can be hard to treat, but effective first treatments may help people live longer and healthier lives. This approval offers a new first treatment for some mCRPC.

About these treatments

Xtandi is standard hormone therapy used to treat mCRPC. It works by blocking testosterone.

Talzenna is a type of known as a . Several different PARP inhibitors are used to treat mCRPC. In addition to being used for prostate cancer, PARP inhibitors also treat certain breast, ovarian and pancreatic cancers.

The research behind the FDA approval

This approval is based on the results of a clinical trial called TALAPRO-2. Half of the participants in the trial took Xtandi with Talzenna. The other half took Xtandi and a sugar pill (). Neither the participants nor the doctors knew who took Talzenna and who took the placebo. Talzenna and Xtandi improved outcomes for all people with mCRPCs. However, people whose tumors had mutations in certain genes responded especially well to this drug combination.

People who took Talzenna went longer without their cancer growing or spreading than participants who received the placebo. Early results suggest that people with a BRCA2 mutations may respond especially well to Talzenna. The drug greatly reduced the risk of cancer spreading in people with a BRCA2 mutation compared to people without a BRCA2 gene mutation.

Side effects

The most common side effects of Talzenna were low red blood cells and fatigue. Participants in the trial also experienced other side effects, including lower appetite, dizziness, nausea, fractures and changes to taste. Low mineral (sodium, calcium, magnesium and potassium) levels were also common.

Among people taking Talzenna, about 2 in 5 needed at least one blood transfusion, and 1 in 5 needed multiple transfusions. Two people on the trial developed leukemia.

What does this mean for me?

Experts recommend that everyone with mCRPC have genetic testing for an inherited mutation linked to prostate cancer. Results from this test may affect your treatment options and may also help your relatives learn about their risk for cancer and take steps to prevent cancer. If you have mCRPC and have not had genetic testing, ask your doctor for a referral for genetic counseling and testing.

Experts also recommend that people with mCRPC have tumor testing to see if they would benefit from treatment with a targeted therapy. If you have not had tumor testing or you are unsure if your tumor tissue has been tested, ask your doctor about ordering additional tests. If genetic or tumor testing shows that you have a mutation in BRCA1, BRCA2, ATM, ATR, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2 or RAD51C, you may benefit from treatment with Talzenna. If you have a mutation in a different gene, you may still benefit from a PARP inhibitor or another type of targeted therapy.

If you have not had surgery to remove both testicles ( orchiectomy) you may need to take a drug which blocks testosterone production.

Reference

FDA approves with for HRR gene-mutated metastatic castration-resistant prostate cancer. FDA news release. June 20, 2023.

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 10/2/23

Questions To Ask Your Doctor

Should I have genetic testing for a mutation in genes linked to prostate cancer?
Should I have tumor testing?
Is Talzenna or another PARP inhibitor an option for me?
Will my health insurance pay for Talzenna?

Open Clinical Trials

The following studies look at PARP inhibitors and similar agents for treating people with advanced prostate 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 PARP inhibitor to treat people with some advanced solid tumors, including prostate cancer.
NCT05005728: XmAb®20717 Alone or in Combination With Chemotherapy or Targeted Therapy in Patients With Metastatic Castration-Resistant Prostate 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 metastatic castration-resistant prostate cancer who have been treated with at least 2 prior lines of treatment.
NCT05417594: Study of the PARP inhibitor AZD9574 Alone and Combined with Other Cancer Medicines to Treat People with Advanced Solid Cancers (CERTIS1 Study). This study looks at a new PARP inhibitor 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 prostate cancer can be found here.

Updated: 11/03/2024

Guidelines

The National Comprehensive Cancer Network guidelines recommend genetic counseling and testing for the following people with prostate cancer who have:

a tumor test result that suggests an inherited mutation
- for example, a tumor with a BRCA1, BRCA2 or ATM mutation 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
prostate cancer that has spread to the
localized prostate cancer (hasn’t spread beyond the prostate) that is considered very high-risk or high-risk
intermediate-risk prostate 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
- metastatic, regional, very-high-risk, or high-risk prostate cancer at any age
one or more close relatives with prostate 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, prostate or other cancers

Speak with a genetic counselor if you have questions about whether you meet guidelines for genetic testing.

Updated: 02/01/2024

Update: New first-line treatment option for metastatic prostate cancer

RELEVANCE

Relevance: Medium-High

Research Timeline: Post Approval

What is this update about?

Why is this update important?

About these treatments

The research behind the FDA approval

Side effects

What does this mean for me?

Reference

Questions To Ask Your Doctor

Open Clinical Trials

Guidelines

Expert Guidelines

Knowledge Can Save Lives

Update: New first-line treatment option for metastatic prostate cancer

RELEVANCE

Relevance: Medium-High

Research Timeline: Post Approval

What is this update about?

Why is this update important?

About these treatments

The research behind the FDA approval

Side effects

What does this mean for me?

Reference

Questions To Ask Your Doctor

Open Clinical Trials

Guidelines

Related Resources

Expert Guidelines

Knowledge Can Save Lives