Guideline: ASCO guidelines recommend olaparib for people with early-stage, high-risk breast cancer and an inherited BRCA mutation

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Contents

At a glance Clinical trials
Updated guidelines Guidelines
What does this mean for me? Questions for your doctor
In-depth: Research behind the update Resources

 

GUIDELINE AT A GLANCE

What is this guideline about?

The American Society of Clinical Oncology (ASCO) updated its guidelines on the management of hereditary breast cancer. The new guidelines now include a recommendation to add one year of the oral PARP inhibitor olaparib as maintenance therapy for people with early-stage (or nonmetastatic), HER2-negative breast cancer who have an inherited BRCA1 or BRCA2 mutation and who are at high risk for recurrence.

 

Why is this guideline important?

Most people with early-stage breast cancer may be treated successfully and never have their cancer return. Some people, however, particularly those with large tumors, several positive lymph nodes or triple-negative breast cancer may have an increased risk for recurrence after treatment ends.

Several methods are used to treat early-stage breast cancer, including surgery, radiation therapy and hormone therapy. In people with HER2-positive breast cancer, a year of targeted therapy such as Herceptin (used for HER2-positive breast cancers) may be used after treatment to keep cancer from coming back. Until olaparib, no targeted therapy was available to specifically keep cancer from returning in people with a BRCA1 or BRCA2 mutation.

PARP inhibitors are a type of targeted therapy that was developed to kill cancer cells in people with a BRCA mutation. These medicines prevent cancer cells from repairing DNA damage, leading to cancer cell death. PARP inhibitors for breast cancer are only approved to treat people with metastatic breast cancer.

In June 2021, the early results of the large OlympiA study were published. OlympiA looked at whether treatment with a PARP inhibitor could improve outcomes in women with earlier-stage breast cancer (see our In-depth section for more details). Based on these results ASCO has updated its 2020 guidelines on the treatment of hereditary breast cancer to recommend a year of treatment with the oral PARP inhibitor olaparib after the completion of chemotherapy for people with all the following:

  • early-stage breast cancer
  • HER2-negative breast cancer
  • an inherited mutation in a BRCA1 or a BRCA2 gene
  • an increased risk for recurrence

 

Updated guidelines

The guidelines below are based on results from the OlympiA trial, a phase 3 clinical trial that included 1,836 people with early-stage breast cancer and a BRCA1 or BRCA2 mutation. In this study, people who received the PARP inhibitor olaparib as an add-on treatment after initial therapy (e.g., surgery, chemotherapy, etc.) had reduced cancer recurrence and prolonged life. (All clinical trial participants had HER2-negative breast cancer.)

Based on these results, ASCO updated their recommendations to include offering one year of olaparib to the following people with early-stage breast cancer and a BRCA1 or BRCA2 mutation after completion of neoadjuvant or adjuvant chemotherapy and local treatment (surgery and, or radiation).

  • For people with triple-negative breast cancer who had surgery to remove their cancer before chemotherapy:
    • anyone with a tumor that was larger than 2 cm (3/4 inch)
    • anyone with 1 or more positive lymph nodes
  • For people with triple-negative breast cancer who had neoadjuvant chemotherapy:
    • anyone with residual cancer found at the time of the surgery
  • For people with ER-positive, HER2-negative cancer who had surgery to remove the cancer first (before chemotherapy or hormone therapy):
    • anyone with 4 or more positive lymph nodes
  • For people with ER-positive, HER2-negative cancer who had neoadjuvant therapy
    • anyone with residual cancer found at the time of surgery and a high risk for recurrence based on a “CSP+EG score” (a score used to predict outcomes after neoadjuvant chemotherapy) of 3 or higher 

 

What does this mean for me?

If you have a BRCA1 or BRCA2 mutation and you have been diagnosed with early-stage, HER2-negative breast cancer, you may benefit from additional treatment with olaparib.

If you have been diagnosed with early-stage, HER2-negative breast cancer and you do not know if you have a BRCA1 or BRCA2 mutation, genetic testing for an inherited mutation can help you learn if you might benefit from additional treatment with olaparib.

Although use of olaparib has been added to the ASCO and NCCN guidelines for early-stage breast cancer, it is important to note that olaparib has not yet received FDA approval in the early-stage breast cancer setting, and some health plans may not cover the cost for this treatment.

 

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posted 8/6/21

 

References

ASCO Releases Rapid Guideline Recommendation Update for Certain Patients With Hereditary Breast Cancer. American Society of Clinical Oncology. Published June 15, 2021.

Tung N, Boughey J, Pierce L, et al. Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline. Journal of Clinical Oncology. 2020 Jun 20;38(18):2080-2106. Published online April 3, 2020.

Tutt ANJ, Garber JE, Kaufman B, et al. OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. New England Journal of Medicine. 2021 Jun 24;384(25):2394-2405. Published ahead of print June 3, 2021.

 

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 HER2-negative breast cancer and an inherited BRCA mutation

This article is also relevant for:

People with breast cancer

People newly diagnosed with cancer

Be part of XRAY:

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  
    • Triple-negative breast cancer at any age 
    • Two separate breast cancer diagnoses
    • Eastern European Jewish ancestry and breast cancer at any age 
    • Metastatic breast cancer 
    • Testing of your tumor shows a mutation in a gene that is associated with hereditary cancer
    • HER2-negative 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
    • Triple-negative breast cancer
    • Male breast cancer, ovarian cancer, pancreatic cancer, or metastatic prostate cancer at any age
    • Two separate cancer diagnoses 
    • Prostate cancer at age 55 or younger or metastatic prostate cancer 

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

The National Comprehensive Cancer Network has guidelines on treating breast cancer in people with an inherited BRCA1 or BRCA2 mutation, with early-onset breast cancer. NCCN recommends for people who are at high risk for recurrence, consider adjuvant olaparib for one year after chemotherapy is completed. 

Updated: 11/23/2021

Questions to Ask Your Doctor

  • Are PARP inhibitors recommended for my type of breast cancer?
  • Will my insurance pay for PARP inhibitor treatment?
  • Should I be tested for an inherited mutation in a BRCA1 or BRCA2 gene or another gene that is linked to breast cancer?
  • I have a mutation in a gene other than BRCA1 or BRCA2; would PARP inhibitors be helpful for treating my cancer?
  • How long will I have to use PARP inhibitors?
  • What are the side effects of PARP inhibitors?

Open Clinical Trials

  • NCT04481113- Abemaciclib and Niraparib Before Surgery for the Treatment of Hormone Receptor-Positive, HER2-Negative Breast Cancer. This phase I trial tests the side effects and best dose of abemaciclib (a kinase inhibitor) and niraparib (a PARP inhibitor) in treating patients with breast cancer that is positive for estrogen or progesterone receptors (hormone receptor-positive [HR+]) and HER2 negative. Giving these two drugs together before surgery may reduce the size of the tumor.
  • NCT04584255-Niraparib + TSR042 In BRCA-Mutated Breast Cancer This research study involves pre-operative therapy that is specifically targeted for breast cancer in individuals with BRCA mutations.
    • The names of the study drugs involved in this study are:
      • Niraparib (Zejula)
      • Dostarlimab

Open Clinical Trials

The following are PARP inhibitor studies enrolling people with early stage breast cancer.  

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

Updated: 11/24/2021

Who covered this study?

Physician’s Weekly

ASCO Updates Recommendations for Managing Hereditary Breast Cancer This article rates 4.0 out of 5 stars

Oncology Nursing News

New ASCO Guideline Recommends Adjuvant Olaparib for Patients with Hereditary Breast Cancer This article rates 4.0 out of 5 stars

How we rated the media

IN-DEPTH: RESEARCH BEHIND THE UPDATE

 

Background

OlympiA Trial

ASCO recently updated its guidelines on the management of hereditary breast cancer to include the use of olaparib for early-stage breast cancer in people with an inherited BRCA mutation. This change was based on data from the OlympiA phase 3 clinical trial.

Olaparib is a PARP inhibitor, a class of drugs that target cancers with defects in homologous repair. Olaparib is used throughout cancer care to improve treatment outcomes. It is FDA-approved as adjuvant therapy for ovarian cancer to sustain treatment response in women who have responded at least partially to chemotherapy. Olaparib is approved to treat men whose prostate cancer no longer responds to medical therapy and has progressed.

For breast cancer, research has shown olaparib treatment to be advantageous for BRCA1 or BRCA2 mutations and advanced breast cancer. Before these studies, there has been a lack of data regarding the benefit of PARP inhibitors in people with BRCA1 or BRCA2 mutation with early-stage breast cancer.

 

Researchers of this study wanted to know

The researchers wanted to know if adding a year of adjuvant olaparib to standard-of-care treatment would be beneficial for people with BRCA1 or BRCA2 mutation who have early-stage, HER2-negative breast cancer.

 

Populations looked at in this study

The study enrolled 1,836 people with an inherited BRCA1 or BRCA2 mutation who had early-stage, HER2-negative breast cancer and who were considered to have a high risk for recurrence. Both women and men, as well as people with triple-negative breast cancer and hormone-positive breast cancer, were included in the study population.

All patients were required to have completed local therapy (surgery with or without radiation therapy) from two to 12 weeks before entering the trial. Systemic therapies that were undergone by participants before the study could include neoadjuvant chemotherapy, adjuvant chemotherapy and hormone therapy.

 

Study design

This was a randomized, double-blind study. Patients were randomly assigned to one of two groups:

  • The olaparib group received 300mg of olaparib twice daily for one year
  • The placebo group received a sugar pill (placebo) twice daily for one year

 

Participants were monitored for:  

  • recurrence of the original breast cancer.
  • new occurrence of cancer.
  • overall survival.
  • Safety, side effects and quality of life in participants for more than 3 years.

 

Study findings

At the 3-year assessment, research results showed that:

  • recurrence of cancer in the same breast or new cancer in the opposite breast or nearby lymph nodes was less likely to occur in the olaparib group (occurred in 11.5% of patients) compared with the placebo group (occurred in 19.4% of patients).
  • distant cancer (metastasis) occurred in 9.7% of patients in the olaparib group and 16.6% of patients in the placebo group.
  • 6.4% of people died of cancer in the olaparib group and 9.4% of people died of cancer in the placebo group.
  • Although adverse events were more likely to occur in patients taking olaparib compared with placebo, the events were consistent with adverse events associated with the product label (e.g., increased anemia and decreased white blood cell counts).

 

The results presented were preliminary. Participants will continue to be followed for a total of 10 years.

 

Strengths and limitations

Strengths

  • This is a large, international, phase 3, double-blinded, randomized study that was powered to show overall survival, disease-free survival, safety and quality of life outcomes.
  • The study built on prior studies that showed olaparib benefited people with advanced breast cancer who had an inherited BRCA1 and BRCA2 mutation.

 

Limitations

OlympiA is an international study, which includes sites in North and South America, Europe, the Middle East and Asia. These preliminary study results did not mention race and ethnicity. This is important because mutations in the BRCA1 or BRCA2 genes can be prevalent among certain racial and ethnic groups, including people of Caribbean and Nigerian descent. While there is no indication that olaparib would act differently in different racial groups, specific data from this study is lacking.

 

Context

PARP inhibitors are FDA-approved to treat advanced breast cancer in patients with inherited BRCA1 or BRCA2 mutations. Research showed that PARP inhibitors as a single-agent delayed recurrence of cancer by three to four months in women with BRCA mutation and metastatic breast cancer compared with patients who were treated with chemotherapy as a single-agent. In addition, women in the PARP inhibitor group were more likely to respond to treatment.

The OlympiA trial shows the benefits of the PARP inhibitor olaparib for patients with an inherited BRCA1 or BRCA2 mutation with early-stage, HER2-positive, high-risk breast cancer. Oral medication may be used to improve treatment outcomes for this population.

 

Conclusions

The current data from the OlympiA Trial suggests that adjuvant olaparib was effective in reducing recurrence and metastasis of cancer and cancer-related death in patients with a BRCA1 or BRCA 2 mutation. These findings suggest that more options may be available for people with BRCA mutations and early-stage breast cancer.   

 

Share your thoughts on this XRAY review by taking our brief survey.
posted 8/6/21

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