The FDA has approved olaparib (Lynparza®, AstraZeneca) for the adjuvant treatment of patients with deleterious or suspected deleterious germline BRCA–mutated, human epidermal growth factor receptor 2 (HER2)–negative high-risk early breast cancer who have previously received adjuvant or neoadjuvant chemotherapy. Olaparib is a poly–adenosine diphosphate ribose polymerase (PARP) inhibitor and is the first approved medication targeting BRCA mutations in early breast cancer.
"Approximately 5% of unselected patients with breast cancer carry germline BRCA1 or BRCA2 mutations (now termed variants) that are either pathogenic or likely pathogenic," wrote Andrew Tutt, MBChB, PhD, Director of the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research in London, and colleagues, in their publication of the phase 3 OlympiA trial (NCT02032823) results, on which the approval was based. "In the OlympiA trial, we hypothesized that olaparib would provide benefit as an adjuvant therapy for patients with germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant–associated breast cancer who have a high risk of recurrence despite standard-of-care local and systemic therapy."
The trial enrolled 1,836 patients with germline BRCA–mutated HER2-negative high-risk early breast cancer previously treated with at least six cycles of adjuvant or neoadjuvant chemotherapy containing anthracyclines, taxanes or both. Patients were randomized in a 1:1 ratio to receive 300 mg olaparib or placebo taken orally twice daily for one year. The primary end point was invasive disease–free survival, which was defined as the time from randomization until the date of first recurrence, including invasive locoregional or distant recurrence, contralateral invasive breast cancer, new cancer, or death by any cause. Secondary end points included distant disease–free survival, overall survival, and safety.
Olaparib produced a statistically significant three-year invasive disease–free survival rate of 86% compared with 77% in the placebo arm, with 106 events of invasive disease or death (12%) in the olaparib arm and 178 events (20%) in the placebo arm. Overall survival was significantly improved with olaparib, with 75 deaths (8%) occurring in the olaparib arm and 109 deaths (12%) occurring in the placebo arm.
Adverse events experienced by ≥10% of patients receiving olaparib included nausea, fatigue and asthenia, anemia, vomiting, headache, diarrhea, leukopenia, neutropenia, decreased appetite, dysgeusia, dizziness, and stomatitis.
"Among patients with high-risk HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive disease or distant disease than was placebo," concluded Dr. Tutt and colleagues in their publication in the New England Journal of Medicine. "Olaparib had limited effects on global patient-reported quality of life."
The recommended dose of olaparib is 300 mg taken orally twice daily, with or without food, for up to one year.
For More Information
Lynparza® (olaparib) prescribing information (2022). AstraZeneca. Available at: https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/00997c3f-5912-486f-a7db-930b4639cd51/00997c3f-5912-486f-a7db-930b4639cd51_viewable_rendition__v.pdf
US Food & Drug Administration (2022). FDA approves olaparib for adjuvant treatment of high-risk early breast cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olaparib-adjuvant-treatment-high-risk-early-breast-cancer
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