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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Monday, March 14, 2022
On March 11, the U.S. Food and Drug Administration (FDA) approved the PARP inhibitor olaparib (Lynparza) for adjuvant treatment of patients with deleterious or suspected deleterious germline BRCA-mutated HER2-negative high-risk early-stage breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. In addition, the FDA approved the BRACAnalysis CDx test for use as a companion diagnostic to identify patients with germline BRCA-mutated HER2-negative, high-risk early-stage breast cancer who may benefit from olaparib treatment.
This approval is based on the randomized, double-blind, placebo-controlled OlympiA study (ClinicalTrials.gov identifier NCT02032823). The study consisted of 1,836 patients with germline BRCA-mutated HER2-negative high-risk early-stage breast cancer who completed definitive local treatment and at least six cycles of neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes, or both. Patients received either 1 year of olaparib tablets at 300 mg orally twice daily or placebo, at a ratio of 1:1.
The primary efficacy endpoint was invasive disease–free survival, for which there were 106 events (12%) in the olaparib arm and 178 events (20%) in the placebo arm (hazard ratio = 0.58; 95% confidence interval = 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. The most common adverse reactions (≥ 10%) in the OlympiA study were nausea, fatigue, 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. Patients must be selected for therapy based on an FDA-approved companion diagnostic for olaparib.
U.S. Food and Drug Administration
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