Study: Promising early results for treating metastatic prostate cancer
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STUDY AT A GLANCE
What is this study about?
The TALAPRO-1 study showed that is a safe and effective treatment for castration-resistant cancer (mCRPC) in people with mutations in repair genes. The ongoing TALAPRO-2 study is looking at how well together with the androgen receptor inhibitor enzalutamide worked to treat mCRPC in people with or without mutations in repair genes.
Why is this study 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.
() is in a class of drugs called PARP inhibitors. PARP inhibitors have been useful in the treatment of several breast, ovarian, pancreatic and cancers associated with inherited mutations or tumor mutations in repair genes. is FDA-approved to treat breast cancer, but it is not yet received approval for cancer treatment.
TALAPRO-2 is an ongoing study looking at how well combined with the androgen receptor inhibitor enzalutamide (Xtandi) works to treat mCRPC in people with or without inherited or tumor mutations in repair genes.
This review covers results from the TALAPRO-1 study and the early results from the TALAPRO-2 study.
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:
- decreased appetite
- low platelet counts
- low white blood cell counts
- No treatment-related deaths occurred.
The TALAPRO-2 study is comparing treatment with together with enzalutamide to treatment with enzalutamide 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 enzalutamide significantly improved progression-free survival, regardless of mutation status when this combination was used as a first-line treatment for mCRPC.
Among participants who received plus enzalutamide (402), progression-free survival was 37 percent better compared to participants (403) who received enzalutamide 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 enzalutamide alone (however data is not complete for the plus enzalutamide group)
- Progression-free survival was improved among participants who received plus enzalutamide compared to those who received enzalutamide 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 enzalutamide compared to 16 months for those who received enzalutamide 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 enzalutamide compared to almost 23 months for those who received enzalutamide alone.
- Although the overall survival data is not complete, it is so far favoring those who received plus enzalutamide compared to those who received enzalutamide alone.
- The time to reduced quality of life was significantly longer in the plus enzalutamide group (31 months) compared to the enzalutamide alone group (25 months).
- Side effects were seen in 80% of patients taking plus enzalutamide and in 41% of patients taking enzalutamide alone.
- The most common side effects were anemia and certain low blood cell counts in the plus enzalutamide arm. Hypertension, anemia and fatigue were the most common side effects in the arm.
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 enzalutamide or abiraterone (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 inherited mutation 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 enzalutamide for the treatment of mCRPC.
Strengths and limitations
- 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.
- 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.
What does this mean for me?
While TALAPRO-2 is ongoing, these early results show significantly improved progression-free survival among participants who received plus enzalutamide compared to participants who received enzalutamide alone. While this was true regardless of whether a participant had an inherited or tumor mutation in genes involved in repair, the benefit is more apparent in patients who did have inherited or tumor mutations in repair genes. Side effects do occur and drug cost should be considered. Final overall survival information that is underway will be important to evaluate to determine when the combination may be most appropriate. While not yet FDA-approved, this combination may become a new standard of care option for people with mCRPC.
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 either or olaparib; both are approved PARP inhibitors. You may also qualify for a research study looking at PARP inhibitors or other treatments for mCRPC.
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 enzalutamide 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) + enzalutamide (ENZA) versus (PBO) + ENZA as first-line (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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This article is relevant for:
People with metastatic castration-resistant prostate cancer (mCRP)
This article is also relevant for:
People with prostate cancer
People with castration-resistant prostate cancer
People with metastatic or advanced cancer
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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 .
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 inherited mutation (for example, a , or mutation in the tumor that 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 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.
- With my diagnosis of mCRPC, should I consider genetic testing for an inherited mutation?
- 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?
The following studies are looking at PARP inhibitors and similar agents for treating people with advanced cancer.
- NCT04592237: Chemotherapy, and for the Treatment of Aggressive Variant Cancer. This study will look at how well the combination of chemotherapy drugs (such as cabazitaxel and carboplatin), a PARP inhibitors (), and an agents (cetrelimab) works for treating people with a rare type of cancer known as aggressive variant cancer (AVPC).
- NCT04821622: TALAPRO-3: A Clinical Trial in Men with Castration-Sensitive Cancer (mCSPC) and Damage Repair (DDR) Gene Alterations. TALAPRO-3 is a trial for men who have been diagnosed with castration-sensitive cancer (mCSPC) which means that the tumor has spread to other parts of the body but it is still sensitive to hormone therapies.
- NCT05005728: XmAb®20717 Alone or in Combination With Chemotherapy or in Patients With Castration-Resistant Cancer. This study will look at the safety and clinical activity of the drug XmAb20717 alone or in combination with standard-of-care anticancer therapies in patients with castration-resistant cancer who have been treated with at least 2 prior lines of treatment.
- NCT04455750: A Clinical Study Evaluating The Benefit of Adding to Enzalutamide for Men With Prostate Cancer That Has Become Resistant To Testosterone-Deprivation Therapy. This trial is evaluating the benefit of and enzalutamide combination therapy versus enzalutamide alone for the treatment of men with prostate cancer that has become resistant to testosterone-deprivation therapy.
- NCT03317392: Studying the Medication Olaparib Given with Radium-223 for Advanced Cancer with Bone . This study is measuring the best dosage for and side effects of the drug combination olaparib and radium-223 to treat men with mCRPC that has spread to the bones.
- NCT04497844: Treatment for Castration-Sensitive Cancer and Inherited or Tumor Mutations in Damage Repair Genes (Amplitude). The goal of AMPLITUDE is to see if adding to standard of care hormone therapy (ADT) is safe and more effective than standard of care alone. The study is enrolling people who have castration-sensitive cancer and have an inherited or tumor mutation in one of the following genes involved in damage repair: , , , , FANCA,PALB2, RAD51B and RAD54L.
Other clinical trials for people with cancer can be found here.
The following organizations offer peer support services for people with or at high risk for cancer:
- FORCE peer support
- Visit our message boards.
- Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Sign up for our Peer Navigation Program.
- Users are matched with a volunteer who shares their mutation and situation.
- Join our private Facebook group.
- Find a virtual or in-person support meeting.
- Join a Zoom community group meeting.
- Visit our message boards.
- ZERO-The End of Cancer is a nonprofit organization that provides information and support resources for men with cancer.
Who covered this study?
PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer: Whom to Treat? This article rates 4.0 out of 5 stars
TALAPRO-3 Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated Metastatic Castration-Sensitive Prostate Cancer (mCSPC) – Neeraj Agarwal This article rates 2.0 out of 5 stars