FDA grants olaparib priority review in BRCA-mutated HER2-negative high-risk early breast cancer


Olaparib, which was granted priority review by the FDA, has been shown to improve invasive disease-free survival for patients with BRCA-mutated HER2-negative high-risk early breast cancer.

The FDA has granted priority review for olaparib (Lynparza) for patients with BRCA-mutated HER2-negative high-risk early breast cancer who have previously been treated with chemotherapy before or after surgery, according to a press release from the PARP inhibitor’s developer, AstraZeneca.1

Olaparib was assessed as part of the phase 3 OlympiA trial (NCT02032823). which showed that patients had an improvement in invasive disease-free survival (iDFS), reducing the risk of breast cancer recurrence by 42% compared with those in the placebo group (HR, 0.58; 99.5% CI, 0.41-0.82; P <.0001). A prescription drug user fee act date has been set for early 2022.

A total of 1836 patients, including 6 men, were randomly assigned to receive either olaparib at 300 mg or the matching placebo twice daily for 52 weeks.2 In the intent-to-treat population, the median follow-up was 2.5 years. Additionally, 82.2% of patients had triple-negative breast cancer. Half of all patients received adjuvant chemotherapy and half received neoadjuvant chemotherapy. In 72.3% of patients, BRCA1 gene mutations were present, 27.2% had BRCA2mutations, and 0.4% had both BRCA1 and BRCA2 mutations.

At the prespecified interim analysis, the efficacy boundary was crossed. At 3 years, a total of 85.9% of patients in the olaparib group and 77.1% of patients in the placebo group were alive and free of invasive disease. A total of 106 patients in the olaparib group and 178 in the placebo group experienced invasive disease or death.

At 3 years, the distant DFS was 87.5% in the olaparib group and 80.4% in the placebo group. Those who received olaparib had significantly longer distant DFS compared with the placebo group (HR, 0.57; 99.5% CI, 0.39-0.83; P <.001). In the olaparib group, 59 deaths were reported compared with 86 in the placebo group (HR, 0.68; 99% CI, 0.44-1.05; P = .02). In 93% patients in the olaparib group and 95% in the placebo group, the primary cause of death was breast cancer. Two patients who did not have a previous event of invasive disease died in the olaparib group. 

The safety analysis included 911 patients from the olaparib group and 904 in the placebo group. Discontinuation of treatment occurred in 25.9% patients in the olaparib group and 20.7% in the placebo group.

Adverse effects (AEs) of grade 3 or higher in the olaparib group included anemia (8.7%), decreased neutrophil count (4.8%), decreased white-cell count (3.0%), fatigue (1.8%), and lymphopenia (1.2%). Within the placebo group, AEs of grade 3 or higher did not occur in more than 1% of patients. A total of 5.8% patients in the olaparib group and 0.9% in the placebo group received blood transfusions, with 4.1% patients in the olaparib group only receiving 1 transfusion.

Serious AEs were repoted in 8.7% of patients in the olaparib group and 8.4% in the placebo group. In the olaparib group, 1 patient had cardiac arrest that led to death, and 1 patient in the placebo group developed acute myeloid leukemia (AML) and ovarian cancer. AEs of special interest included pneumonitis, radiation pneumonitis, myelodysplastic syndrome, or AML.

In the United States, Olaparib has been previously approved for first-line maintenance treatment of BRCA-mutated ovarian cancer following response to platinum-based chemotherapy, first-line maintenance treatment plus bevacizumab (Avastin) for homologous recombination deficient–positive advance ovarian cancer, and BRCA-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy, with additional indications for treatment in prostate and pancreatic cancer.

This article was originally posted on Cancer Network®.


1. Lynparza granted priority review in the US for BRCA-mutated HER2-negative high-risk early breast cancer. News Release. AstraZeneca. November 30, 2021. Accessed November 30, 2021. https://bit.ly/3llGA9m

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

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