FDA Approves Olaparib as Adjuvant Treatment for High-Risk Early Breast Cancer


Olaparib (Lynparza) approved for patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer.

The FDA has approved olaparib (Lynparza)for the adjuvant treatment of patients with germline BRCA-mutated, human epidermal growth factor receptor 2(HER2)-negative, high-risk early breast cancer who were previously administered chemotherapy prior to or following surgery.1

The approval was based on findings from the multicenter, randomized, placebo-controlled, phase 3 OlympiA trial, during which olaparib showed a 42% improvement in invasive disease-free survival (iDFS) versus placebo, which was deemed statistically significant and clinically meaningful (HR, 0.58; 95% CI, 0.46-0.74; P <.0001).2,3

Further, the study showed that adjuvant olaparib produced a 32% reduction in the risk of disease progression or death versus placebo (HR, 0.68; 95% CI, 0.50-0.91; P = .0091). Safety findings from treatment with olaparib were consistent with what was observed in prior studies.

“Today’s approval of olaparib is great news for patients with a specific inherited form of breast cancer," professor Andrew Tutt, global chair of the OlympiA trial and professor of oncology at The Institute of Cancer Research, London and King’s College London, said in a press release. "Most breast cancers are identified in the early stages and many patients will do very well, but for those with higher risk disease at diagnosis, the risk of cancer returning can be unacceptably high and new treatment options are needed. OlympiA has shown that identifying a BRCA1/2 mutation in women with high-risk disease opens the additional option of eligibility for olaparib treatment, which reduces the risk of recurrence and improves survival for these breast cancer patients.”

OlympiA enrolled 1836 patients with HER2-negative breast cancer with a germline BRCA mutation. Patients were randomized 1:1 to receive 300 mg of oral olaparib twice daily for 1 year (n = 921) or placebo (n = 915). Furthermore, patients had to have been treated for stage II or III breast cancer and have completed surgery and chemotherapy, with or without radiotherapy.

Inclusion criteria also required patients to have a high risk of disease recurrence. Patients previously treated with a PARP inhibitor were not eligible for enrollment. The primary end point was iDFS, with secondary end points including distant disease-free survival (DDFS), overall survival (OS), health-related quality of life, and safety.

The study showed that patients administered olaparib had a 43% decrease in DDFS, including metastatic disease, new cancer, and death due to any cause (stratified HR, 0.57; 99.5% CI, 0.39-0.83; P < .0001). The difference in the 3-year DDFS rate between olaparib and placebo was 7.1% (87.5% vs 80.4%, respectively; 95% CI, 3.0%-11.1%).

At the time of the interim analysis, OS data were immature. Although fewer deaths were reported in patients administered olaparib compared with placebo, OS was not significantly different between the 2 study arms (stratified HR, 0.68; 99% CI, 0.44-1.05; P = .024). The difference in the 3-year OS rate between the olaparib and placebo groups was 3.7% (92.0% vs 88.3%, respectively; 95% CI, 0.3%-7.1%).

Olaparib was not found to increase serious adverse effects (AEs), including hospital admissions or occurrences of other cancers, such as leukemia. Grade 3 or higher AEs were reported more frequently in patients administered olaparib, and included anemia (9%), neutropenia (5%), leukopenia (3%), and fatigue (2%).

The most common AEs of any-grade reported in patients administered olaparib included nausea (57%), fatigue (40%), anemia (23%), vomiting (23%), and headache (20%). The most common AEs of any-grade reported in the placebo arm were fatigue (27%), nausea (23%), headache (17%), diarrhea (14%), and arthralgia (12%).


  1. Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer. AstraZeneca. News release. March 11, 2022. Accessed March 11, 2022. https://bit.ly/3tQePcn
  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
  3. 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
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