The Food and Drug Administration (FDA) has approved Lynparza (olaparib) for the adjuvant treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy.
The approval was based on data from the phase 3 OlympiA trial (ClinicalTrials.gov Identifier: NCT02032823), which evaluated the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, vs placebo in 1836 patients with gBRCAm, HER2-negative high-risk breast cancer who had completed definitive local treatment and neoadjuvant or adjuvant chemotherapy.
Patients were randomly assigned 1:1 to receive olaparib 300mg orally twice daily (n=921) or placebo (n=915) for up to 1 year, or until disease recurrence, or unacceptable toxicity. The primary endpoint was invasive disease free survival, defined as the time from randomization to date of first loco-regional or distant recurrence or new cancer or death from any cause.
Findings showed that treatment with olaparib was associated with a 42% reduction in the risk of invasive breast cancer recurrence, second cancers or death compared with placebo (hazard ratio [HR] 0.58; 95% CI, 0.46-0.74; P <.0001). Additionally, a statistically significant improvement in overall survival was demonstrated in patients in the olaparib arm vs the placebo arm (HR 0.68; 95% CI, 0.50-0.91; P =.0091).
“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 high, and new treatment options are needed,” said Professor Andrew Tutt, global chair of the OlympiA trial and professor of oncology, The Institute of Cancer Research, London, and King’s College London. “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 reduced the risk of recurrence and improved survival for these patients.”
The safety profile of olaparib was consistent with that seen in previous studies. The most common adverse events reported in the OlympiA trial were nausea, fatigue, anemia, vomiting, headache, diarrhea, leukopenia, neutropenia, decreased appetite, dysgeusia, dizziness, and stomatitis.
- Lynparza approved in the US as adjuvant treatment for patients with germline BRCA-mutated HER2-negative high-risk early breast cancer. News release. AstraZeneca and Merck. March 11, 2022. Accessed March 14, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/lynparza-approved-in-the-us-as-adjuvant-treatment-for-patients-with-germline-brca-mutated-her2-negative-high-risk-early-breast-cancer.html
- FDA approves Lynparza® (olaparib) as adjuvant treatment for patients with germline BRCA-mutated (gBRCAm), HER2-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. News release. AstraZeneca and Merck. March 11, 2022. Accessed March 14, 2022. https://www.businesswire.com/news/home/20220311005480/en/FDA-Approves-LYNPARZA%C2%AE-olaparib-as-Adjuvant-Treatment-for-Patients-With-Germline-BRCA-Mutated-gBRCAm-HER2-Negative-High-Risk-Early-Breast-Cancer-Who-Have-Been-Treated-With-Neoadjuvant-or-Adjuvant-Chemotherapy
- Lynparza. Package insert. AstraZeneca Pharmaceuticals LP; 2022. Accessed March 14, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208558s023lbl.pdf