On March 11, 2022, the FDA accelerated the approval of the oral PARP inhibitor olaparib (Lynparza; AstraZeneca) for the adjuvant treatment of adults with HER2-negative, high-risk early breast cancer and deleterious or suspected deleterious germline BRCA mutation after neoadjuvant or adjuvant chemotherapy. Patients must be selected for olaparib therapy for this indication based on an FDA-approved test.
This approval was based on the OlympiA study, a randomized, double-blind, placebo-controlled, international clinical trial of 1836 patients with gBRCAm HER2-negative high-risk early breast cancer and germline BRCA mutation who completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomized in a 1:1 ratio to 1 year of olaparib 300 mg orally twice daily or to placebo. Patients had to have completed ≥6 cycles of neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes, or both. Patients with hormone receptor–positive breast cancer were allowed to continue concurrent treatment with endocrine therapy.
The primary efficacy end point was invasive disease-free survival (IDFS), defined as the time from randomization to the date of first recurrence (ie, invasive locoregional or distant recurrence), contralateral invasive breast cancer, new cancer, or death from any cause.
The IDFS rate was 12% in the olaparib arm and 20% in the placebo arm (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.46-0.74; P <.0001). The IDFS rate at 3 years was 86% (95% CI, 82.8-88.4) with olaparib and 77% (95% CI, 73.7-80.1) with placebo. The overall survival (OS) was an additional efficacy end point. A total of 75 deaths (8%) were reported in the olaparib arm and 109 (12%) in the placebo arm (HR, 0.68; 95% CI, 0.50-0.91; P = .0091). A significant improvement in IDFS and OS was seen in the olaparib arm versus the placebo arm.
The most common (≥10%) adverse reactions in this study were nausea, fatigue (including asthenia), anemia, vomiting, headache, diarrhea, leukopenia, neutropenia, decreased appetite, dysgeusia, dizziness, and stomatitis.
