OlympiA: Game Changer for Breast Cancer Treatment

Few patients with newly diagnosed breast cancer who are eligible for genetic testing get tested. There are more patients with germline BRCA mutations in estrogen receptor (ER)–positive/human epidermal growth factor receptor (HER)–negative breast cancer (~10,000 annually in the U.S.) than patients with germline BRCA mutations in triple-negative breast cancer (TNBC; ~4800 annually), even though such mutations are more common in TNBC (14.8%, versus 5%). The poly (adenosine diphosphate–ribose) polymerase inhibitors olaparib and talazoparib are approved treatments for metastatic germline BRCA-mutated breast cancer. Now, data from the OlympiA trial confirm significant benefit from olaparib in patients with high-risk HER-negative BRCA-mutated early-stage breast cancer.

A total of 1836 patients were randomized to olaparib or placebo for 1 year after completing standard adjuvant or neoadjuvant chemotherapy and local treatment. For patients receiving neoadjuvant chemotherapy, high risk was defined as TNBC with no pathologic complete response (pCR) or ER-positive with no pCR and CPS+EG score >3 (CPS+EG includes pre- and postsurgery stage, ER status, and nuclear grade). For patients receiving adjuvant chemotherapy, high risk was defined as TNBC stage ≥pT2 or ≥pN1 or ER positive with ≥4 positive nodes. Most patients (94%) received an anthracycline/taxane regimen, and 26% also received platinum-based therapy; 18% had ER-positive tumors.

With a median follow-up of 2.5 years, 3-year invasive disease-free survival (iDFS) — the primary outcome — was significantly higher in the olaparib group than the placebo group (85.9% vs.77.1%). The 3-year overall survival showed a numerical but not statistical advantage for olaparib (92% vs. 88.3%). Olaparib showed an advantage in all subsets analyzed, although confidence intervals for patients with ER-positive tumors and those exposed to platinum were wide due to small numbers. The reduction in iDFS with olaparib was largely accounted for by distant metastatic events. There were no unexpected side effects in the olaparib arm or excess second malignancies.