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Study: Promising early results for treating metastatic prostate cancer

Summary

The TALAPRO studies looked at how well the oral drug Talzenna (talazoparib) works as a treatment for metastatic castration-resistant prostate cancer (mCRPC). The addition of Talzenna to treatment with Xtandi (enzalutamide) increased the time until the cancer got worse or came back (progression-free survival). The greatest benefit was seen in people who had an inherited or tumor mutation in a gene that repairs DNA damage (such as ATM, BRCA1, BRCA2 and others). (Posted 3/1/23)

Update: On June 20, 2023, the Food and Drug Administration (FDA) approved the combination of Talzenna with Xtandi as an initial treatment for some people with mCRPC for people with inherited or tumor mutations in genes that repair DNA damage. 

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Promising early results for treating metastatic prostate cancer

RELEVANCE

Most relevant for: People with metastatic castration-resistant prostate cancer (mCRPC). It may also be relevant for:

  • people with prostate cancer
  • people with castration-sensitive prostate cancer
  • people with metastatic or advanced cancer

Relevance: Medium-High

Strength of Science: High

Research Timeline: Human Research

Relevance Rating Details

What are these studies about?

A series of research studies called TALAPRO looked how well the drug () works for treatment of castration-resistant cancer (mCRPC) in people with certain inherited or tumor mutations.

What type of drug is ? What is a ? 

is a type of drug called a . PARP inhibitors have been useful in the treatment of several different types of cancers associated with a  or inherited mutations or tumor mutations in genes that repair damage. is FDA-approved to treat breast cancer, but it has not yet received approval for cancer treatment.

Why are these studies important?

castration-resistant cancer (mCRPC) no longer responds to standard treatments that block testosterone. People with mCRPC that continues to grow despite treatment have limited treatment options. More effective treatments are needed.

  • The TALAPRO-1 study looked at how safe and effective is for treatment for castration-resistant cancer (mCRPC) in people with mutations in repair genes.
  • The ongoing TALAPRO-2 study is comparing how well treatment with  together with the hormonal treatment Xtandi () works compared to Xtandi alone for treating people with mCRPC.

Study findings

This review covers results from the TALAPRO-1 study and the early results from the TALAPRO-2 study.

TALAPRO-1 results

TALAPRO-1 showed that is safe and effective for treating people who have mCRPC with inherited mutations or tumor mutations in repair genes.

  • 31 of 104 (30%) participants’ cancers decreased in size.
  • Cancers decreased in size only in participants with , , or mutations.
    • Cancer response rates were best among participants with or mutations—almost half of these participants' tumors responded to .
  • None of the 22 participants with mutations in ATR, , FANCA, , MRE11A, or had decreased cancer size.  
  • No significant safety issues occurred when participants took .

TALAPRO-2 results

Early TALAPRO-2 results were reported in February of 2023. 

  •  plus Xtandi significantly improved progression-free survival, regardless of mutation status when this combination was used as a treatment for mCRPC. 

Participants who received plus Xtandi had a longer period of time before their cancer got worse or came back (progression-free survival) compared to participants who received Xtandi alone. However, participants with a mutation in a repair gene benefited more than those without a mutation

  • Among participants with inherited or tumor mutations in a repair gene, progression-free survival was 28 months for those who received  plus Xtandi compared to 16 months for those who received Xtandi alone. 
  • Although the overall survival data is not complete, it is so far favoring those who received  plus Xtandi compared to 16 months for those who received Xtandi alone.
  • The time before quality of life got worse was significantly longer in the  plus Xtandi group (31 months) compared to the Xtandi alone group (25 months).

Side effects

  • Side effects were common but similar to earlier studies of PARP inhibitors.
    • Side effects were seen in 80% of people taking  plus Xtandi .
    • Side effects were seen in 41% of patients taking Xtandi alone.
  • The most common side effects of  were:
    • low red blood cell counts (anemia)
    • nausea
    • decreased appetite
    • weakness
    • low platelet counts
    • low white blood cell counts
  • No treatment-related deaths occurred.

What does this mean for me?

While TALAPRO-2 is ongoing, these early results show improved outcomes among participants who received and Xtandi compared to participants who received Xtandi alone. The benefit is more apparent in patients who have inherited or tumor mutations in , or other genes that repair damage. Side effects do occur. While not yet FDA-approved, this combination may become a new standard of care option for people with mCRPC. Two PARP inhibitors have been approved by the for treating mCRPC. The , Lynparza () is approved to treat mCRPC that has progressed on the drugs Xtandi or Zytiga () in people with a mutation in , , or another gene linked to damage repair. The Rubraca () is approved to treat mCRPC in people who have an in or (found through genetic testing) or a tumor mutation in or (found through tumor testing or ).

If you have been diagnosed with mCRPC and your cancer has progressed on standard care, genetic testing and tumor testing may help you learn if you would benefit from treatment with a . You may also qualify for a research study looking at PARP inhibitors or other treatments for mCRPC.

Reference

de Bono JS, Mehra N, Scagliotti GV, et al. monotherapy in castration-resistant cancer with repair alterations (TALAPRO-1): an , phase 2 trial. Lancet Oncol. 2021;22(9):1250-1264.

Agarwal N, Azad A, Shore ND, et al. plus in castration-resistant cancer: TALAPRO-2 phase III study design. Future Oncol. 2022;18(4):425-436.

Agarwal N, Azad A, Carles J et al. TALAPRO-2: Phase 3 study of (TALA) + (ENZA) versus (PBO) + ENZA as (1L) treatment in patients (pts) with castration-resistant cancer (mCRPC). J Clin Oncol 41, 2023 (suppl 6; abstr LBA17).

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 3/1/23

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • With my diagnosis of mCRPC, should I consider genetic testing for an ?
  • Should I have additional tumor testing to see what other treatments may be available for me?
  • What are the treatment options for my prostate cancer?
  • Is therapy appropriate for me? Am I eligible for any clinical trials of PARP inhibitors?

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: 09/11/2023

Related resources
Related resources

The following resources focus on  cancer. 

Updated: 08/06/2022

Study findings

This review covers results from the TALAPRO-1 study and the early results from the TALAPRO-2 study.

TALAPRO-1 

TALAPRO-1 showed that has acceptable safety and is effective for treating people who have mCRPC with inherited mutations or tumor mutations in repair genes.

Results of TALAPRO-1

  • 31 of 104 (30%) participants’ cancers decreased in size.
  • Cancers decreased in size only in participants with , , or mutations.
    • Cancer response rates were best among participants with or mutations—almost half of these participants' tumors responded to .
  • None of the 22 participants with mutations in ATR, , FANCA, , MRE11A, or had decreased cancer size.  
  • No significant safety issues occurred when participants took .
  • Side effects were common but similar to earlier studies of PARP inhibitors.
    • Nearly half of the participants had low red blood cell counts, which was the most common side effect.
    • Other common side effects of were:
  • nausea
  • decreased appetite
  • weakness
  • low platelet counts
  • low white blood cell counts
  • No treatment-related deaths occurred.

TALAPRO-2

The TALAPRO-2 study is comparing treatment with together with to treatment with alone in people with or without mutations in repair genes. Early TALAPRO-2 results were reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium in February of 2023. 

Early results of TALAPRO-2

plus significantly improved progression-free survival, regardless of mutation status when this combination was used as a treatment for mCRPC. 

Among participants who received plus (402), progression-free survival was 37 percent better compared to participants (403) who received alone. However, participants with a mutation in a repair gene benefited more than those without a mutation.

  • Preliminary progression-free survival was significantly improved for the group compared to 22 months for participants who received alone (however data is not complete for the plus group)
  • Progression-free survival was improved among participants who received plus compared to those who received alone, regardless of their mutation status.         
    • Among participants with inherited or tumor mutations in a repair gene, progression-free survival was 28 months for those who received plus compared to 16 months for those who received alone. 
    • Among participants with no known inherited or tumor mutation in a repair gene, progression-free survival has not been achieved among those who received plus compared to almost 23 months for those who received alone.
  • Although the overall survival data is not complete, it is so far favoring those who received plus compared to those who received alone.
  • The time to reduced quality of life was significantly longer in the plus group (31 months) compared to the alone group (25 months).
  • Side effects were seen in 80% of patients taking plus and in 41% of patients taking alone.
    • The most common side effects were anemia and certain low blood cell counts in the plus arm. Hypertension, anemia and fatigue were the most common side effects in the arm.

Conclusions

Two PARP inhibitors have been approved by the for treating mCRPC. The olaparib (Lynparza) is approved to treat mCRPC that has progressed on the drugs or (Zytiga) in people with a mutation in , , or another gene linked to a certain type of damage repair. The rucaparib () is approved to treat mCRPC in people who have an in or (found through genetic testing) or a tumor mutation in or (found through tumor testing or ).

While does not have approval to treat cancer, the has granted Priority Review for plus for the treatment of mCRPC.

Strengths and limitations

Strengths

  • TALAPRO-2 is a large multi-site study being conducted in 26 countries and 32 states in the U.S. that includes people from diverse backgrounds. It is to participants and their providers.
  • The results of TALAPRO-2 will address the limitations of TALAPRO-1.

Limitations

  • TALAPRO-1 was a small early-phase study where all participants received the same treatment. It was not designed to determine whether works better than other treatments. Participants could have mutations in one of 11 genes. The number of participants was too small to identify differences between responses in people with different mutations.
  • The majority (87%) of TALAPRO-1 participants were white; given the small study size, this limits the ability to conclude whether works similarly in people of all racial and ethnic backgrounds

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

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network has guidelines regarding which  cancer patients should undergo genetic counseling and testing. Men with the following factors should speak with a genetics expert about genetic testing:

  • A tumor test result that suggests an (for example, a ,  or  mutation in the tumor that 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.
  • Intraductal/cribriform cells found by pathology.
  • Cancer that is categorized as very high or high risk based on pathology.
  • A diagnosis of male breast cancer.
  • Eastern European (Ashkenazi) Jewish ancestry. 
  • One or more first-, second- or third-degree relatives with breast cancer diagnosed 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: 03/01/2023

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?

How we rated the media

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Article Rating Details

OncLive: PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer: Whom to Treat?
Rating: 4.0 Stars

  • This is written for a professional healthcare audience and may be difficult for the average reader to understand.
  • No critical appraisal of TALAPRO or statistics are provided.

Uro Today: TALAPRO-3 Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) – Neeraj Agarwal
Rating: 2.0 Stars

  • This article does not critically evaluate the study.
  • Only the study authors are cited; no comments from external experts are included.
  • The article includes some scientific inaccuracies.

Study Rating Details

Relevance: Medium High

  • The study is relevant to people with prostate cancer but talazoparib is not yet FDA approved for prostate cancer treatment nor is it approved in combination with enzalutamide.
  • These findings are only relevant for people with a mutation in a DNA repair gene and those who do not have an inherited or tumor mutation in a DNA repair gene.

Scientific Strength: High

  • TALAPRO-1 was an early phase 2 study.  The TALAPRO-3 study, while still ongoing, is a well-designed phase 3 randomized control trial, which will address the unknowns of TALAPRO-1.

Research Timeline:  Human research

  • TALAPRO-2 is phase 3 trial with the potential to change the standard of care for people with mCRPC. The drug combination being tested is undergoing FDA review.