Adding Olaparib to Treatment for Early-Stage BRCA+ Breast Cancer Yields Benefits, Study Shows

ASCO officials characterized the results as practice changing and said they highlighted the need for genetic testing in patients who receive a diagnosis of high-risk breast cancer.

Giving olaparib to patients with certain BRCA-mutated breast cancer for 1 year after they were treated with chemotherapy, surgery, or radiation significantly improved disease-free survival, according to results presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Results from the OlympiA trial are important because they show that adding olaparib, a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, also benefits patients with early-stage disease, in addition to the drug’s known benefits in similar patients with metastatic disease. Patients in the study had BRCA 1/2 germline, or inherited, mutations and high-risk, early-stage cancer that was negative for human epidermal growth factor receptor 2 (HER2).

Results released late Thursday were simultaneously published in the New England Journal of Medicine. ASCO officials characterized the results as practice changing and said they highlighted the need for genetic testing in patients who receive a diagnosis of high-risk breast cancer.

Inherited mutations cause between 5% and 10% of breast cancers, but these cancers can be more aggressive and deadly. While the lifetime risk of breast cancer is about 12% for women overall, for women with BRCA mutations, it’s 72%. These women also tend to develop breast cancer at younger ages and in both breasts than those without the mutation.

“OlympiA’s findings highlight the need for genetic testing for BRCA mutations in patients diagnosed with high-risk early-stage breast cancer. These results could have an important impact on treatment decisions for this patient population, possibly including the use of a PARP inhibitor in the adjuvant setting,” ASCO President Lori J. Pierce, MD, FASTRO, FASCO, said in a statement.

The study randomized 1836 patients to receive olaparib or placebo. Results at a prespecified event-driven interim analysis were as follows:

  • The 3-year invasive disease–free survival was 85.9% in the olaparib group and 77.1% in the placebo group, for a difference of 8.8 percentage points; 95% CI, 4.5 to 13.0. The hazard ratio (HR) for invasive disease or death was 0.58; 99.5% CI, 0.41-0.82; P < .001.
  • The 3-year distant disease–free survival was 87.5% in the olaparib group and 80.4% in the placebo group, for a difference of 7.1 percentage points; 95% CI, 3.0 to 11.1; The HR for distant disease or death was 0.57; 99.5% CI, 0.39 to 0.83; P < .001.
  • The 3-year estimated overall survival was greater with olaparib but not statistically significant at the time of the interim analysis.
  • Adverse events (AEs) were consistent with those in earlier studies with olaparib. Serious AEs did not occur more frequently with olaparib than with placebo.

“Olaparib had limited effects on global patient-reported quality of life,” the authors wrote in NEJM.

The results are the first to report the effects of a PARP inhibitor as an adjuvant therapy on survival endpoints, which lead author Andrew Tutt, MB ChB, PhD, FMedSci, said suggest a possible addition to the standard of care for patients with germline BRCA1/2 mutation-associated early breast cancer whose risk of cancer recurrence is higher.

More follow-up is planned, according to the study authors.

Olaparib is sold as Lynparza by AstraZeneca/Merck; AstraZeneca funded the study with the National Cancer Institute.


Tutt ANJ, Garber JE, Kaufman B, et al. for the OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. Published online June 3, 2021. doi: 10.1056/NEJMoa2105215

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