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

Relevance: Medium-High

Research Timeline: Post Approval

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What is this update about?

The FDA (Food and Drug Administration) approved Talzenna together with Xtandi as a first-line treatment for people with metastatic castration-resistant prostate cancer (mCRPC). This approval is for people who have an inherited mutation or tumor mutation in the following genes: BRCA1, BRCA2, ATM, ATR, CDK12, CHEK2, FANCA, MLH1*, MRE11A, NBN, PALB2 or RAD51C. Talzenna is given with Xtandi, which is already used to treat metastatic prostate cancer.

*Although MLH1 mutations are included in the approval, MLH1 works differently to repair DNA 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 targeted therapy known as a PARP inhibitor. 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 (placebo). 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 (bilateral orchiectomy) you may need to take a drug which blocks testosterone production.

Reference

FDA approves talazoparib with enzalutamide 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