FDA Approves Olaparib CDx to Detect BRCA in High Risk Early Breast Cancer

The FDA approved the BRACAnalysis CDx test for use as a companion diagnostic with adjuvant olaparib to identify patients with germline BRCA-mutated for patients with HER2 negative, high-risk early-stage breast cancer.

BRACAnalysis CDx test for use as a companion diagnostic with adjuvant olaparib (Lynparza) to identify patients with germline BRCA-mutated (gRBCAm) has been approved by the FDA for patients with HER2 negative, high-risk early-stage breast cancer who may benefit from treatment with the PARP inhibitor, according to Myriad Genetics, Inc.1

The combination is intended for HER2-negative high-risk patients who have undergone treatment with chemotherapy prior to or following surgery.

“This most recent regulatory approval confirms the benefits of using biomarkers to help guide care for patients with breast cancer,” said Nicole Lambert, chief operating officer, Myriad Genetics. “Data from the OlympiA trial and numerous other clinical studies continue to demonstrate the power of BRACAnalysis CDx as an effective test for patients deciding on their best treatment options. More patients with breast cancer now potentially qualify for BRCA testing.”

The BRACAnalysis CDx test is created to detect and interpret germline BRCA1 and BRCA2 variants. It works to identify deleterious germline BRCA variants as well as suspected ones in patients with HER2 negative high-risk early breast cancer.

“Studies have demonstrated that PARP inhibitors are highly effective in patients with BRCA1/BRCA2 mutations. Once we identify these patients, they will have more options for treatment,” said Thomas Slavin, MD, chief medical officer, Myriad Genetics.2 “This important advancement underscores the need for breast cancer patients being evaluated for approved therapies to know their BRCA status with an FDA-approved test right after diagnosis to help ensure they will receive the best available therapy. Additionally, the quick adoption of OlympiA criteria by guideline committees greatly supports the advancement of genomics in clinical care.”

Approval of olaparib comes from the results of the phase 3 OlympiA trial (NCT02032823) which assessed the efficacy and safety of olaparib versus the placebo in patients with germline BRCA1/2-mutant high-risk HER2-negative primary breast cancer.3 The trial showed olaparib to have a 42% improvement in invasive disease-free survival (iDFS) versus placebo, and was deemed as statistically significant and clinically meaningful (HR, 0.58; 95% CI, 0.46-0.74; P <.0001).4,5

OlympiA enrolled 1836 patients, including 6 men, with HER2-negative breast cancer with a germline BRCAmutation. Patients were randomized 1:1 to receive either 300 mg of oral olaparib twice daily for 1 year (n = 921) or placebo (n= 915).

Patients had to have been treated for stage II or III breast cancer and have completed surgery and chemotherapy, with or without radiotherapy. The randomization was stratified by hormone receptor status, prior neoadjuvant versus adjuvant chemotherapy and prior platinum use for breast cancer. Patients received the study treatment for up to a maximum of 12 months.

Enrollment in the trial was open to patients who had a high risk of disease recurrence while patients who were previously treated with a PARP inhibitor were not eligible for enrollment. The primary end point was iDFS, with secondary end points consisting of distant disease-free survival (DDFS), overall survival (OS), health-related quality of life, and safety.

At the primary analysis, 284 events of invasive disease or death (86% of the primary-analysis target of 330 such events) were observed with a median follow-up of 2.5 years in the intention-to-treat population and 3.5 years in the mature cohort.

The efficacy boundary was crossed during a prespecified interim analysis. At 3 years, 85.9% of those in the olaparib group and 77.1% of those in the placebo were alive and disease-free. In the olaparib group, patients experienced longer invasive disease than in the placebo group (HR, 0.58; 99.5% CI, 0.41-0.82; P<.001). A total of 59 patients died in the olaparib group vs 86 in the placebo group (HR, 0.68; 99% CI, 0.44-1.05; P = .02). Between the 2 groups, the primary cause of death was breast cancer, and in the olaparib group, 2 patients died without a previous event of invasive disease.

Olaparib had a 43% decrease in DDFS, including metastatic disease, new cancer, and death due to any cause (stratified HR, 0.57; 99.5% CI, 0.39-0.83; P<.0001). In the 3-year DDFS rate between olaparib and the placebo, the difference was 7.1% (87.5% vs 80.4%, respectively:95% CI, 3.0%-11.1%).

The study also showed adjuvant olaparib to produce a 32% reduction in the risk of disease progression or death versus placebo (HR, 0.68; 95% CI, 0.50-0.91; P=.0091). The safety analysis included 1815 patients between both groups. The median number of days at the protocol dose was 338 in the olaparib group compared to 358 in the placebo group. Early discontinuation from recurrence occurred in 236 patients in the olaparib group and 187 in the placebo group. Safety findings from treatment with olaparib were consistent with that observed in prior studies.

In 228 patients in the olaparib group versus 47 in the placebo group, dose reductions were necessary. Adverse events (AEs) lead to permanent discontinuation in 90 patients in the olaparib group and 38 in the placebo group. Reasons for discontinuation in the olaparib group included nausea (2.0%), anemia (1.8%), fatigue (1.3%), and decreased neutrophil count (1.0%) with AEs leading to permanent discontinuation seen in 90 patients in the olaparib group and 38 in the placebo group. Reasons for discontinuation in the olaparib group were nausea (2.0%), anemia (1.8%), fatigue (1.3%), and decreased neutrophil count (1.0%).

AEs grade 3 or higher in the olaparib group consisted of anemia (8.7%), decreased neutrophil count (4.8%), decreased white-cell count (3.0%), fatigue (1.8%), and lymphopenia (1.2%). AEs grade 3 or higher did not occur in more than 1% of patients in the placebo arm. Additionally, blood transfusions were administered to 53 patients in the olaparib group and 8 in the placebo group, and 37 patients in the olaparib group had 1 transfusion.

In the olaparib group, serious AEs were observed in 79 patients compared to 76 in the placebo group. AEs of special interest included pneumonitis, radiation pneumonitis, myelodysplastic syndrome or acute myeloid leukemia, and new primary cancer. Further follow-up is needed in order to determine AEs of special interest.


1. Myriad Genetics receives FDA approval of BRACAnalysis CDx as a companion diagnostic for lynparza in early breast cancer. Myriad Genetics. News Release. March 11, 2022. Accessed March 14, 2022. https://bit.ly/3I9iQ0E

2. Sekine M, Nishino K, Enomoto T. BRCA Genetic Test and Risk-Reducing Salpingo-Oophorectomy for Hereditary Breast and Ovarian Cancer: State-of-the-Art. Cancers. 2021; 13(11):2562. https://doi.org/10.3390/cancers13112562

3. Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer. AstraZeneca. News release. March 11, 2022. Accessed March 14, 2022. https://bit.ly/3tQePc

4.Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394-2405. doi:10.1056/NEJMoa2105215

5. Tutt A, Garber JE, Kaufman B, et al. OlympiA: a phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer. J Clin Oncol. 2021;39(suppl 15):LBA1. doi:10.1200/JCO.2021.39.15_suppl.LBA1

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