FDA Approves Olaparib for Adjuvant Treatment of High-Risk Early Breast Cancer

Approval was based on a randomized, double-blind, placebo-controlled, international study (OlympiA; NCT02032823) of 1,836 patients with gBRCAm HER2-negative high-risk early breast cancer who completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomized 1:1 to receive either one year of olaparib 300 mg tablets orally twice daily or placebo. Patients must have completed at least six cycles of neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes, or both. Patients with hormone receptor–positive breast cancer continued concurrent treatment with endocrine therapy per local guidelines.

The primary efficacy endpoint was invasive disease-free survival (IDFS), defined as the time from randomization to date of first recurrence defined as invasive loco-regional, distant recurrence, contralateral invasive breast cancer, new cancer, or death from any cause. For IDFS, 106 events (12%) occurred in the olaparib arm and 178 events (20%) in the placebo arm (HR 0.58; 95% CI = 0.46, 0.74; p < 0.0001). IDFS at three 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 (OS), with 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 = 0.0091). Patients in the olaparib arm demonstrated a statistically significant improvement in IDFS and OS compared with the placebo arm.

The most common adverse reactions reported in 10% or more of patients 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 one year.

View the full prescribing information for olaparib (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208558s023lbl.pdf).

The review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with Health Canada and Switzerland’s Swissmedic. The application reviews are ongoing at other regulatory agencies.

The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment.

FDA granted the application priority review. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate (mailto:OCE’s%20Project%20Facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).