FDA Approves Adjuvant Olaparib in BRCA-Mutated HER2-Negative High-Risk Early Breast Cancer

The FDA approval of olaparib comes from the results of the phase 3 OlympiA trial that tested the treatment vs a placebo.

The FDA has approved adjuvant olaparib (Lynparza) for patients with BRCA-mutated HER2-negative high-risk early breast cancer who have undergone treatment with chemotherapy prior to or following surgery, according to a press release from AstraZeneca.1

The approval was supported by results of the phase 3 OlympiA trial (NCT02032823) which assessed the use of adjuvant olaparib vs placebo in patients with germline BRCA1/2-mutant high-risk HER2-negative primary breast cancer. In the trial, olaparib demonstrated a clinically meaningful improvement in invasive disease-free survival (iDFS) and a reduction in risk of invasive recurrence, second cancers, or death by 42% compared with placebo (HR, 0.58; 95% CI, 0.46-0.74; P <.0001). Moreover, updated findings from the study highlighted a statistically significant and clinically meaningful improvement in overall survival, with a 32% reduction in the risk of death vs placebo (HR, 0.68; 95% CI, 0.50-0.91; P = .0091).

“This important approval gives [patients with] early-stage breast cancer in the US with a germline BRCA mutation a new targeted therapy option in the adjuvant setting starting today. [Olaparib] reduces the risk of disease recurrence in these high-risk patients and now new data confirm it also significantly extends patients’ lives versus placebo. These data underline the importance of germline BRCA testing as soon as possible after diagnosis to identify patients that may be eligible for Lynparza,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, said in a press release.

A total of 1836 patients including 6 men were randomly assigned to either treatment group.2 At the primary analysis, 284 events of invasive disease or death 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. Patients received 300 mg of oral olaparib or placebo twice daily for 52 weeks.

During the prespecified interim analysis, the efficacy boundary was crossed. At 3 years, 85.9% of those in the olaparib group and 77.1% of those in the placebo were alive and disease-free. Patients experienced longer iDFS in the olaparib group than the placebo group (HR, 0.58; 99.5% CI, 0.41-0.82; P <.001). Invasive disease or death was reported in 106 patients in the olaparib group and 178 in the placebo group.

The distant DFS rate at 3 years was 87.5% in the olaparib group and 80.4% in the placebo group (HR, 0.57; 99.5% CI, 0.39-0.83; 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. In the olaparib group, 2 patients died without a previous event of invasive disease.

The safety analysis included 1815 patients between both groups. The median number of days at the protocol dose was 338 in the olaparib group and 358 in the placebo group. Early discontinuation from recurrence occurred in 236 patients in the olaparib group and 187 in the placebo group.

Adverse effects (AEs) grade 3 or higher in the olaparib group were 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. 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.

Serious AEs were observed in 79 patients in the olaparib group and 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 required to determine AEs of special interest.

Dose reductions were necessary in 228 patients in the olaparib group vs 47 in the placebo group, 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%).


  1. 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 11, 2022. https://bit.ly/37ouloq
  2. 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