FDA Approves Companion Diagnostic for Olaparib in Early Breast Cancer

The FDA has approved the BRACAnalysis CDx assay for use as a companion diagnostic to select patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer who may derive clinical benefit from treatment with olaparib.

The FDA has approved the BRACAnalysis CDx assay for use as a companion diagnostic to select patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer who may derive clinical benefit from treatment with olaparib (Lynparza).1

The in vitro diagnostic device is intended for the qualitative detection and classification of variants in the protein-coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes through the utilization of genomic DNA extracted from whole blood specimens.2 By leveraging polymerase chain reaction and Sanger sequencing, the test can detect single nucleotide variants and small insertions and deletions.

On March 11, 2022, the regulatory agency approved olaparib as an adjuvant treatment in patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer who have received prior chemotherapy before or after surgery.3 The decision was based on data from the phase 3 OlympiA trial (NCT02032823), in which the agent was found to improve invasive disease-free survival (iDFS) by 42% compared with placebo (hazard ratio [HR], 0.58; 95% CI, 0.46-0.74; P < .0001).4,5

The agent also reduced the risk of disease progression or death by 32% vs placebo (HR, 0.68; 95% CI, 0.50-0.91; P = .0091). The overall survival (OS) data with this approach is slated for presentation at the ESMO virtual plenary on March 16, 2022.

“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,” Thomas Slavin, MD, chief medical officer of Myriad Genetics, stated in a press release. “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.”

The prospective, multicenter, multinational, double-blind OlympiA trial enrolled patients with a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant with high-risk, HER2-negative primary breast cancer following definitive local treatment and neoadjuvant or adjuvant chemotherapy.

Patients needed to have completed all local therapy at least 2 weeks, and no more than 12 weeks, before entering the trial. Platinum chemotherapy was permitted. If patients received neoadjuvant chemotherapy, they were not able to receive chemotherapy following surgery. Those treated with neoadjuvant chemotherapy needed to have residual invasive disease in the breast or the resected lymph nodes. Those who received adjuvant chemotherapy for hormone receptor–positive disease needed to have at least 4 pathologically confirmed positive lymph nodes.

A total of 1836 participants were randomized 1:1 to receive oral olaparib at a twice daily dose of 300 mg (n = 921) or matching placebo (n = 915) for 52 weeks. Stratification factors included hormone receptor status (positive vs negative), timing of prior chemotherapy (neoadjuvant vs adjuvant), and use of platinum chemotherapy for current disease (yes vs no).

The primary end point of the trial was iDFS, and key secondary end points included distant DFS (DDFS), OS, and safety.

The baseline characteristics were noted to be balanced between the 2 treatment arms. The median age in the investigative arm was 42 years (range, 36-49) vs 43 years (range, 36-50) in the control arm. Regarding mutational status, 71.3% of those who received olaparib had a BRCA1 mutation, 28.3% had BRCA2, and 0.2% had both; in the placebo arm, these rates were 73.2%, 26.1%, and 0.5%, respectively.

In the investigative arm, 50.1% of patients previously received adjuvant chemotherapy, 49.9% had prior neoadjuvant chemotherapy, 94.6% received a regimen containing an anthracycline and taxane, 0.8% received an anthracycline regimen without taxane, 4.7% had a taxane regimen without an anthracycline, and 0.8% received less than 6 cycles of neoadjuvant or adjuvant chemotherapy.

Additionally, 73.2% and 73.9% of those in the investigative and control arms, respectively, did not receive platinum-based neoadjuvant or adjuvant therapy. Moreover, 18.2% of those on the investigative arm had hormone receptor–positive and HER2-negative disease, as did 17.2% of those on the control arm; 81.5% and 82.8% of patients, respectively, had triple-negative breast cancer.

Regarding menopausal status, 62.2% and 60.7% of patients, respectively, were premenopausal, and 37.8% and 39.3% of patients, respectively, were postmenopausal. Most patients on both the investigative and control arms had a mastectomy for their primary breast cancer, at 75.8% and 73.6%, respectively.

Additional data from the trial published in the New England Journal of Medicine showed that the 3-year DDFS rate was 87.5% in the olaparib arm vs 80.4% in the placebo arm, translating to a difference of 7.1 percentage points (95% CI, 3.0%-11.1%). Moreover, DDFS was found to be significantly longer in those who received olaparib vs placebo, with a HR of 0.57 (99.5% CI, 0.39-0.83; P < .001).

Moreover, fewer deaths were reported on the investigative arm vs the control arm, at 59 and 86, respectively (HR, 0.68; 95% CI, 0.44-1.05; P = .02), although the between-arm difference was not found to cross the prespecified multiple-testing procedure boundary for significance of P < .01.

Findings from subgroup analyses continued to demonstrate benefit with adjuvant olaparib over placebo with regard to iDFS, regardless of the kind of germline BRCA mutation present, hormone receptor status, and timing of prior chemotherapy.

A total of 911 patients in the olaparib arm and 904 patients in the placebo arm comprised the safety analysis. In the investigative arm, the median number of days at the protocol dose was 338; in the control arm, the median number of days was 358. Moreover, 25.9% of those in the olaparib arm vs 20.7% of those on the placebo arm discontinued treatment early.

The most common grade 3 or higher toxicities reported in the olaparib arm included anemia (8.7%), decreased neutrophil count (4.8%), decreased white cell count (3.0%), fatigue (1.8%), and lymphopenia (1.2%). No grade 3 or higher toxicities were reported in 1% or more of those on the placebo arm. Blood transfusions occurred in 5.8% and 0.9% of those in the investigative and control arms, respectively.

Moreover, serious adverse effects were reported in 8.7% of those who received olaparib vs 8.4% of those given placebo. One patient in the investigative arm went into cardiac arrest and this resulted in death. In the control arm, 1 patient each had acute myeloid leukemia (AML) and ovarian cancer, which resulted in death. Toxicities of special interest included pneumonitis, radiation pneumonitis, myelodysplastic syndrome (MDs), or AML, and a new primary cancer beyond MDS or AML.


  1. Myriad Genetics receives FDA approval of BRACAnalysis CDx as a companion diagnostic for Lynparza in early breast cancer. News release. Myriad Genetics, Inc.; March 11, 2022. Accessed March 14, 2022. https://bit.ly/35ZZbTP
  2. BRACAnalysis CDx. Myraid Genetics, Inc. website. Accessed March 14, 2022. https://bit.ly/3w5LRbm
  3. Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer. News release. AstraZeneca; March 11, 2022. Accessed March 14, 2022. https://bit.ly/3tQePcn
  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