Olaparib Receives FDA Approval for Postoperative Adjuvant Treatment of Early-Stage Breast Cancer

Patients with pathogenic (harmful) or suspected pathogenic germline (inherited) BRCA mutations (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative high-risk breast cancer who had received neoadjuvant or adjuvant chemotherapy were the population for whom olaparib (Lynparza, AstraZeneca) received FDA approval on 11 March 2022 for postoperative adjuvant (protective) treatment.

Olaparib, one of the new-generation cancer drugs, is a PARP inhibitor and received its first FDA approval for ovarian cancer in 2017. It was subsequently approved in 2018 for stage 4 breast cancer positive for inherited BRCA mutations. Further FDA approvals followed: first-line maintenance therapy for BRCA-mutant ovarian cancer in 2018; first-line maintenance therapy for BRCA-mutant metastatic pancreatic cancer in 2019; first-line maintenance therapy for HRD-positive advanced ovarian cancer with bevasizumab in 2020; and metastatic castration-resistant prostate cancer with HRR gene mutations, also in 2020.

December 2022 Update: With longer follow-up of 3.5 years, adjuvant olaparib also demonstrated an overall survival benefit (4-year overall survival of 90 percent versus 86 percent). Based on these data, we recommend oral adjuvant olaparib twice daily for one year for BRCA carriers with early-stage HER2-negative breast cancer who meet the high-risk criteria from the OlympiA trial.

High-Risk Criteria According to the OlympiA Trial

pTY: pathological complete response.

FDA Approval Based on the OlympiA Trial

FDA approval is based on OlympiA, a randomized (1:1), double-blind, placebo-controlled, international trial involving 1836 patients with gBRCAm HER2-negative high-risk early breast cancer who had completed local treatment (neoadjuvant or adjuvant chemotherapy).

Patients were randomized to receive 300 mg olaparib tablets orally twice daily for 1 year or placebo.

Patients had to complete at least 6 cycles of neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes or both.

Patients with hormone receptor-positive breast cancer were allowed to continue concurrent endocrine therapy according to local guidelines.

The primary efficacy endpoint targeted in the study was defined as the time from study entry to the date of first recurrence (cancer recurrence), termed disease-free survival.

First recurrence was defined as locoregional cancer recurrence, distant metastasis, cancer in the opposite breast, a new cancer or death from any cause.

Results

• For disease-free survival, there were 106 events (12%) in the olaparib arm and 178 events (20%) in the placebo arm (HR 0.58; 95% CI: 0.46, 0.74; p<0.0001).
• At year 3, disease-free survival 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=0.0091).

The most common (≥10%) adverse effects in the OlympiA trial were nausea, fatigue (including asthenia), anemia, vomiting, headache, diarrhea, leukopenia, neutropenia, decreased appetite, taste disturbances, dizziness and stomatitis.

The recommended olaparib dose is 300 mg orally twice daily, with or without food, for up to one year.