FDA Grants Priority Review to Olaparib for Adjuvant Treatment BRCA-mutated HER2- High-Risk eBC

Findings from the phase 3 OlympiA led to the filing of a supplemental new drug application for olaparib as adjuvant treatment of BRCA-mutated HER2-negative high-risk early breast cancer.

The FDA has accepted the supplemental new drug application (sNDA) for olaparib (Lynparza) and granted it priority review for the adjuvant treatment of patients with BRCA-mutated HER2-negative high-risk early breast cancer who have already been treated with chemotherapy either before or after surgery, announced Astra Zeneca, in a press release.1

Astra Zeneca and development partner Merck & Co., Inc submitted the sNDA based on results from the phase 3 OlympiA clinical trial, in which olaparib demonstrated significantly longer survival free of invasive or distant disease compared with placebo. The Prescription Drug User Fee Act target action date has been set to the first quarter of 2022.

OlympiA (NCT02032823) was randomized, double-blinded, and placebo-controlled with parallel group assignment. The study was conducted across multiple centers in the United States, South America, Canada, Europe, Asia, and the Oceania. Invasive disease-free survival (iDFS) was the primary end point of the study, and the secondary end points included overall survival (OS), distant disease-free survival, effect on the incidence of new primary breast and gynecologic cancers, effect on the existence of the deleterious ovarian, exposure to olaparib, and quality of life. Investigators also assessed the safety and tolerability of olaparib in the study.2

At a median follow-up of 2.5 years in 1836 patients with previously treated BRCA-mutated HER2-negative high-risk early breast cancer, olaparib showed a 3-year iDFS rate 85.9% compared with 77.1% in the placebo group (HR, 0.58; 99.5% CI, 0.41-0.82; P <0.001). The 3-year distant disease-free survival was 87.5% with olaparib versus 80.4% with placebo (HR, 0.57; 99.5% CI, 0.39 to 0.83; P <0.001). In terms of OS, fewer deaths occurred in the olaparib arm compared with the placebo arm, but the difference was not significant (HR, 0.68; 99% CI, 0.44-1.05; P =0.02).3

To evaluate safety, 1815 patients from the olaparib arm and 905 from the placebo arm were evaluated. Adverse events (AEs) occurred in a minimum of 10% of patients in each treatment arm. The most common any-grade AEs in the olaparib group were nausea (56.9%), fatigue (40.1%), and anemia (23.5%). 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. The higher grade AEs observed included anemia (8.7%), decreased neutrophil count (4.8%), decreased white-cell count (3.0%), fatigue (1.8%), and lymphopenia (1.2%). Grade 3 or higher AEs were uncommon in the placebo arm. Blood transfusion were need in 5.8% of patients treated with olaparib compared with 0.9% in the placebo arm.

Serious AEs occurred in 8.7% of patients in the olaparib arm compared with 8.4% of patients in the placebo arm. There was 1 death in the study related to a cardiac AE. More than 25% of patients had early treatment discontinuations due to disease recurrence.

Olaparib is already FDA approved for the treatment of patients with germline BRCA-mutated HER2-negative metastatic breast cancer. An FDA approval based on the OlympiA trial will expand the use of olaparib to treatment in the adjuvant setting.1


1. Lynparza granted priority review in the US for BRCA-mutated HER2-negative high-risk early breast cancer. News release. Astra Zeneca. November 30, 2021. Accessed November 30, 2021. https://bit.ly/3pgi1M6

2. Olaparib as adjuvant treatment in patients with germline BRCA mutated high risk HER2 negative primary breast cancer (OlympiA). Clinicaltrials.gov. Accessed November 30, 2021. https://bit.ly/3D97ozM

3. 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