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

Contents

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. Update: Based on results from the OlympiA Study, on March 11, 2022 the FDA approved olaparib as adjuvant treatment for people with an inherited BRCA mutation who have been diagnosed with early-stage HER2-negative breast cancer and 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.