FDA Approves Olaparib as Adjuvant Treatment for BRCA Mutated HER2-Negative Breast Cancer

FDA approval has been granted to adjuvant olaparib for the treatment of BRCA-mutated, HER2-negative breast cancer.

The FDA has approved the use of olaparib (Lynparza) as adjuvant treatment for patients with BRCA-mutated HER2-negative high-risk early breast cancer that were previously treated with chemotherapy before or after surgery, according to a press release.1

“FDA approval is essential to making olaparib available to appropriate patients across the insurance spectrum, and perhaps to expand access to genetic testing for newly diagnosed breast cancer patients,” Judy E. Garber, MD, chief of the Division for Cancer Genetics and Prevention, Susan F. Smith Chair, and institute physician at Dana-Farber Cancer Institute as well as a professor of Medicine at Harvard Medical School told Targeted Oncology™,” in an interview.

The basis of the approval included results from the phase 3 randomized, double-blinded, and placebo-controlled OlympiA trial (NCT02032823). Results showed that olaparib demonstrated significantly longer invasive disease-free survival (iDFS) with a 3-year iDFS rate of 85.9% in the olaparib group compared to 77.1% in the placebo group, achieveing a 42% reduction in the risk of invasive breast cancer recurrences, second cancers, or death (HR, 0.58; 99.5% CI, 0.41-0.82; P <0.001).2

“In women with a germline pathogenic/likely pathogenic variant in BRCA1 or BRCA2 and a new HER2-negative breast cancer at high risk of recurrence, the addition of 1 year of olaparib 300 mg BID significantly improves invasive disease-free survival following completion of all standard surgery, neoadjuvant chemotherapy and radiation therapy, explained Garber. “To fully benefit, women with ER-positive or negative HER2-negative breast cancer who have enough disease to have been eligible for the OlympiA trial, should undergo genetic testing as part of their early evaluation to be able to plan for possible adjuvant olaparib.”

The study looked at 1836 patients, with a median follow up of 2.5 years, to determine efficacy of the treatment and found a 3-years distant disease-free survival of 87.5% in the olaparib group versus 80.4% in the placebo group (HR, 0.57; 99.5% CI, 0.39 to 0.83; P <0.001). However, while the olaparib arm had fewer deaths compared to the placebo arm the difference was not significant (HR, 0.68; 99% CI, 0.44-1.05; P =0.02).

In the trial, researchers evaluated safety in 911 patients from the olaparib arm and 904 in the placebo arm with adverse events (AEs) occurring in a minimum of 10% of patients in each arm. The most common AEs in the treatment arm were nausea (56.9%), fatigue (40.1%), and anemia (23.5%), while in the placebo arm, the most common any-grade AEs were nausea (23.3%), fatigue (27.1%), and headache (16.8%). 

Grade 3 or higher AEs occurred in more than 1% of the olaparib arm including anemia (8.7%), decreased neutrophil count (4.8%), decreased white-cell count (3.0%), fatigue (1.8%), and lymphopenia (1.2%). Serious AEs occurred in about 8% in both groups with 1 death in the study due to a related cardiac AE. Over 25% of patients had to discontinue treatment early due to disease recurrence.

BRCA status is not itself a prognostic factor. However, there is other progress at this time, including adjuvant immunotherapy and newer agents moving into the adjuvant setting, that may be improving outcomes for these patients, Garber stated.


1. Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer. News release Astra Zeneca. March 11, 2022. Accessed March 11, 2022. https://bit.ly/3tN27va

2. Tutt AN, Garber JE, Kaufman, B et al, Adjuvant olaparib for patients with brca1- or brca2-mutated breast cancer. N Engl J Med. 2021; 384:2394-2405. doi: 10.1056/NEJMoa2105215

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