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Study: Research on the PARP inhibitor talazoparib (Talzenna) for early-stage breast cancer is promising

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Contents

At a glance                  In-depth                                
Findings               Limitations                
Clinical trials Resources
Questions for your doctor  


STUDY AT A GLANCE

This study is about:

Whether the Talzenna () is effective for treating patients with cancer that can be surgically removed in patients with inherited  mutations.

Why is this study important?

Treating breast cancer before surgery (also known as therapy) is used to reduce the size of the tumor and the risk of cancer recurrence. PARP inhibitors are a type of that has been approved for treating breast cancer in people with mutations. This study is one of the first to test whether a used alone (without chemotherapy) before surgery is effective for treatment of breast cancer.

Study findings: 

This pilot study included 20 patients. The goal was to test the effectiveness and side effects of () alone when taken for 6 months before surgery in patients with I, II or III breast cancer who had a hereditary mutation.

The majority of patients treated with () before surgery had a pathologic complete response [pCR]), meaning that they had no detectable cancer in their breast or at the time of surgery. The study measured residual cancer burden (RCB), the amount of tumor that remains after treatment.

  • 10 of 19 (53%) patients had a pathologic complete response (pCR) and had no remaining cancer burden after treatment.
  • 12 of 19 (63%) of participants had no or low remaining cancer burden.
     
  • The majority of participants with either triple-negative or HR-positive breast cancer had no or low remaining cancer burden.
     
  • 53% of participants with mutations had low or no residual tumor.
  • 100% of participants with mutations had low or no residual tumor.
     
  • Patients with several rare types of breast cancer had pathologic complete response.

The side effects observed were tolerable tor most patients.

  • The most common milder side effects were nausea, fatigue, anemia (low red blood cells), hair loss, dizziness and breathing difficulties.
     
  • The most common severe side effects were anemia and nausea.

What does this mean for me?

Two PARP inhibitors are approved in the U.S. to treat advanced breast and several others for ovarian cancer. As of now, no PARP inhibitors have been approved for breast cancer. Ongoing clinical trials are looking at the effectiveness and safety of these drugs for people in this population.

More research on () as a treatment for breast cancer is needed to determine if this initial study result can be confirmed.

If you have breast cancer and have a mutation, you might consider discussing treatment with your health care provider.

Share your thoughts on this XRAYS article by taking our brief survey.

Posted 10/4/19
 

References

Litton JK, Scoggins ME, Hess , et al. " Talazoparib for patients with operable breast cancer with a germline pathogenic variant." Journal of Clinical Oncology. Published online Aug 28, 2019. DOI: https://doi.org/10.1200/JCO.19.01304.
 

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.

This article is relevant for:

People with early stage breast cancer who have an inherited BRCA mutation

This article is also relevant for:

Men with breast cancer

Triple negative breast cancer

ER/PR +

People with a genetic mutation linked to cancer risk

Breast cancer survivors

Women under 45

Women over 45

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IN-DEPTH REVIEW OF RESEARCH

Study background:

PARP inhibitors block the function of a repair enzyme in cells. Tumor cells of people with inherited mutations or tumor cell that have acquired a mutation can be specifically targeted and destroyed by PARP inhibitors.

Two PARP inhibitors, olaparib (Lynparza) and () are approved for treatment of advanced or breast cancers for people with an inherited mutation in one of the genes. The OlympiAD trial of olaparib (Lynparza) and the EMBRACA trial of () showed that treatment with these drugs lengthened the time until tumors grew and improved quality of life among breast cancer patients compared to patients treated with chemotherapy.

Since PARP inhibitors are useful for treating breast cancer patients, can they be used to treat earlier-stage breast cancer? Typically, patients with BRCA-positive, tumors have been treated with chemotherapy before or at the time of surgery, which improved outcomes, specifically by increasing the frequency of pathologically complete recovery (pCR) or the frequency of clinically undetectable cancer.

The I-SPY trial found improved outcomes when the velociparib was given with traditional chemotherapy (carboplatin plus paclitaxel) compared to another chemotherapy combination. Other combination trials with PARP inhibitors for breast cancer have not shown any improved outcomes; however, in these studies, most participants did not have mutations. If PARP inhibitors work predominantly in people with mutations this may have confused the results.

Could PARP inhibitors alone give a similar or better result than chemotherapy drugs for people with mutations?  Researchers at MD Anderson Cancer Center at the University of Texas tested whether tumors of patients with I to III breast cancer responded to the talazoparib () when it was given before other chemotherapy. Patients with mutations and I to III breast cancer who were treated with for 2 months and then chemotherapy prior to surgery showed a decrease in tumor size.

This result led to this pilot study that looked at whether by itself at the time of surgery improved patient outcomes with tolerable side effects.

Researchers of this study wanted to know:

whether patients with inherited mutations who were treated with () alone for 6 months prior to surgery had undetectable tumors (a pathological complete response) and manageable side effects when compared to patients who were treated with other chemotherapy prior to surgery.

Populations looked at in this study:

Participants were 20 patients with a verified inherited or mutation, I to III breast cancer, and a primary tumor of 1 cm or larger that was imaged by and . Participants were enrolled from August 2016 to September 2017, with a median age of 38 years (range: 23 to 58 years). Although both men and women were eligible, all 20 participants were women. Among the participants:

  • 16 had a mutation
  • 4 had a mutation
  • 15 had
  • 5 had hormone receptor-positive cancer
  • 5 had I cancer
  • 12 had II cancer,
  • 3 had III cancer, including 1 patient with inflammatory breast carcinoma and one with metaplastic chondrosarcomatous carcinoma.

Patients with HER2+ tumors were excluded. Patients were also excluded if they had previous surgery, radiation, or for breast cancer. Patients with prior ductal carcinoma in situ or who had treatment for a previous non-breast cancer at least 5 years prior were still eligible.

Study design:

This pilot study of 20 patients intended to collect preliminary data to demonstrate the usefulness of a larger trial.

Twenty patients underwent a pretreatment biopsy, then took 1 mg of once a day for 6 months, had surgery to remove their tumors and then had postsurgery treatment of their physician’s choice. The study measured residual cancer burden (RCB) or the amount of tumor that remains after treatment and tracked side effects among participants. Patients who had at least 4 months of treatment and surgery within 6 weeks of their last dose were evaluated. One patient received 5 months of therapy, but had an enlarged lymph node and chose to have systemic chemotherapy before surgery. Her information was included for but not for the primary end point of pathologic response.

Study findings: 

The majority of patients treated with () before surgery had a pathologic complete response [pCR]) or no invasive disease in breast and lymph at the time they were evaluated. The study measured residual cancer burden (RCB), the amount of tumor that remains after treatment. A RBC-0 is the same as pathologic complete response. Residual cancer burden of 1 (RCB-1) or more have increasing amounts of tumor remaining.

  • 19 patients were evaluated for residual cancer burden
    • 10 of 19 (53%) had RCB-0 (pathologic complete response [pCR]) or no invasive disease in breast and )
    • 2 of 19 (10%) had RCB-I.
    • 5 of 19 (26%) had RCB-II.
    • 3 of 19 (16%) had RCB-III.
       
  • 12 of 19 (63%) of participants had a low amount or no residual tumor (RCB-0/I).
     
  • The majority of participants with either triple negative or HR-positive breast cancer had low or no residual tumor (RCB-0/I).
    • Among participants with , 57% had low or no residual tumor (RCB-0/I).
    • Among participants with HR-positive breast cancer, 80% had low or no residual tumor (RCB-0/I).
       
  • Among participants with T1 tumors, 83% had low or no residual tumor (RCB-0/I).
  • Among participants with T2 or greater tumors, 54% had low or no residual tumor (RCB-0/I).
     
  • Among participants with mutations, 53% had low or no residual tumor (RCB-0/I).
  • Among participants with mutations, 100% had low or no residual tumor (RCB-0/I).
     
  • The single patients with metaplastic chondrosarcomatous carcinoma, invasive lobular carcinoma, or inflammatory breast cancer all had had no detectable tumor remaining (pCR/RCB-0).

The toxic side effect observed were tolerable tor most patients.
 

  • 11 of 20 (55%) patients completed the trial on the full dose of .
  • 9 of 20 (45%) patients had their doses reduced due to treatment-related anemia.
     
  • Patients with severe toxic side effects (grade 3 or 4) either had doses of reduced by 0.25 mg increments until their side effects were manageable or had a blood transfusion.
    • 2 patients had their dose reduced to 0.75 mg per day
    • 6 patients had their dose reduced to 0.5 mg per day
    • 1 patient had their dose reduced to 0.25 mg per day

The most common less severe side effects were nausea, fatigue, anemia (low red blood cell count), hair loss, dizziness and breathing difficulties.
 

The most common severe side effects were anemia and nausea:

  • 12 of 20 (40%) participants had severe (grade 3 or 4) toxicities
    • 8 patients had severely low red blood cell numbers (grade 3) and required a transfusion.
    • 3 patients had severely low white blood cell numbers (grade 3).
    • 1 patient had very severely low platelet numbers (grade 4).

Limitations:

This trial had many limitations:

  • This was a preliminary study with only 20 participants, intended as a pilot test to determine whether a larger trial was justified. The results are promising, but the numbers are too small to be certain how much is a fluke. A larger study is needed to validate these results.
     
  •  Only a single institution was involved in this study. It is possible that there are additional confounding factors about treatment at this institution that may account for the results. A larger study would ideally be run at multiple institutions to reduce this possibility.
     
  • This trial had no comparison intervention. The number of participants who had  complete reduction of tumor burden (RCB-0) or low residual tumor burden (RCB-1) are promising but can only be compared to data in trials run in other places and under other circumstances. A direct comparison of this treatment regimen versus a current standard treatment is needed to know if this treatment protocol is comparable, better, or worse than chemotherapy for cancer treatment.
     
  • No patient-reported outcome tests were done. Researchers did ask about changes in menstrual cycles, but did not measure the state of participants’ fertility. The researchers point out that many mutation carriers are young and still in the process of family planning. This type of information would be an important addition to future studies.
     
  • Postsurgical treatment in this trial was left up to the surgeon/oncologist's choice. Having a more controlled trial that evaluated specific postsurgical treatments in comparison to treatment would be clarifying.

Conclusions:

In this pilot study, () alone appears to be a promising treatment for patients with mutations who develop breast cancer. An expanded clinical trial with a larger number of participants is needed to determine if this treatment approach is viable.

Share your thoughts on this XRAYS article by taking our brief survey.

Posted 10/4/19
 

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network has guidelines on who should undergo genetic counseling and testing. If you have been diagnosed with breast cancer, you should speak with a genetics expert about genetic testing if any of the following apply to you:     

  • You have a blood relative who has tested positive for an inherited mutation 
  • You have any of the following:  
    • Breast cancer at age 50 or younger  
    • Male breast cancer at any age
    • Ovarian cancer at any age  
    • at any age 
    • Two separate breast cancer diagnoses
    • Eastern European Jewish ancestry and breast cancer at any age 
    • breast cancer 
    • Testing of your tumor shows a mutation in a gene that is associated with
    • breast cancer and high risk for recurrence
    • Lobular breast cancer and a family history of diffuse gastric cancer

OR 

  • You have one or more close family members who have had:  
    • Young-onset or rare cancers 
    • Breast cancer at age 50 or younger
    • Male breast cancer, ovarian cancer, pancreatic cancer, or   cancer at any age
    • Two separate cancer diagnoses 
    • cancer at age 55 or younger or prostate cancer 

The American Society of Breast Cancer Surgeons (ASBrS) released guidelines in 2019 that recommend all women diagnosed with breast cancer have access to genetic testing for inherited mutations in breast cancer genes. 

If you are uncertain whether you meet the guidelines above and you are interested in or considering genetic testing, you should speak with a cancer genetics expert

 

Updated: 11/22/2021

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network has guidelines on treating breast cancer in people with an inherited or mutation, with early-onset breast cancer. For people who are at high risk for recurrence, NCCN recommens considering a year of with olaparib after chemotherapy is completed.  

Updated: 06/06/2022

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • What type of treatment is best for me prior to my breast cancer surgery?
  • Am I eligible for any clinical trials of PARP inhibitors for breast cancer?
  • I have breast cancer; what are the benefits and risks of treatment for me?

Open Clinical Trials
Open Clinical Trials

The following are studies enrolling people with early breast cancer.  

A number of other clinical trials for patients with breast cancer can be found here.

Updated: 03/18/2022

Peer Support
Peer Support

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

Updated: 11/29/2022

Who covered this study?

Healio

Also published in:

Med News Today

Neoadjuvant talazoparib induces pathologic complete response in BRCA-mutated operable breast cancer This article rates 3.5 out of 5 stars

The Oncology Learning Network

Talazoparib Yields Significant Pathologic Complete Response in gBRCA-Positive, Operable Breast Cancer This article rates 2.5 out of 5 stars

How we rated the media

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