On March 11, the U.S. Food and Drug Administration (FDA) approved olaparib (Lynparza) for the adjuvant treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative, high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Patients must be selected for therapy based on an FDA-approved companion diagnostic for olaparib, and Myriad’s BRACAnalysis CDx test was also approved on March 11 for such use.
Approval was based on OlympiA (ClinicalTrials.gov identifier NCT02032823), a randomized, double-blind, placebo-controlled international study of 1,836 patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer who completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned to receive either 300-mg olaparib tablets orally twice daily for 1 year or placebo.
Patients were required to have completed at least six 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 per local guidelines.
The primary efficacy endpoint was invasive disease–free survival, defined as the time from random assignment to date of first recurrence, defined as invasive locoregional, distant recurrence, contralateral invasive breast cancer, new cancer, or death from any cause.
For invasive disease–free survival, there were 106 events (12%) in the olaparib arm and 178 events (20%) in the placebo arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.46–0.74, P < .0001). Invasive disease–free survival at 3 years was 86% (95% CI = 82.8%–88.4%) for patients receiving olaparib and 77% (95% CI = 73.7%–80.1%) for those receiving placebo. An additional efficacy endpoint was overall survival. There were 75 deaths (8%) in the olaparib arm and 109 deaths (12%) in the placebo arm (HR = 0.68, 95% CI = 0.50–0.91, P = .0091). A statistically significant improvement in invasive disease–free survival and overall survival was demonstrated in patients in the olaparib arm compared with the placebo arm.
The most common adverse reactions (≥ 10%) in the OlympiA study were nausea, fatigue (including asthenia), anemia, vomiting, headache, diarrhea, leukopenia, neutropenia, decreased appetite, dysgeusia, dizziness, and stomatitis.
The recommended olaparib dose is 300 mg taken orally twice daily with or without food for up to 1 year.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Health Canada and Switzerland’s Swissmedic. The application reviews may be ongoing at the other regulatory agencies. This also review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review.