Title: Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation

Robson, M. et al.


What You Need to Know:

In patients with human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer with a germline BRCA mutation, treatment with olaparib not only increased median progression-free survival, but also decreased the risk of disease progression or death when compared to standard therapy.

Trial Design:

  • Randomized, open-label, phase 3 study evaluated the benefits of treatment with olaparib in metastatic breast cancer patients with a germline BRCA mutation who had not received more than 2 chemotherapy regimens previously
  • 302 patients were randomized (2:1) to receive 300mg olaparib twice daily (n=205) or standard therapy of 21-day cycles of capecitabine, eribulin, or vinorelbine (n=97)
  • Primary endpoint: progression-free survival (evaluated by blinded independent central review; intention-to-treat analysis)
  • Secondary endpoints: “safety outcomes, overall survival, time from randomization to a second progression event or death after a first progression event (based on investigator assessment), objective response rate (based on blinded independent central review, according to modified RECIST, version 1.1), and scores for health-related quality of life”

Key Outcomes:

  • Median progression-free survival: 7.0 months for olaparib patients vs 4.2 months for standard-therapy patients (HR for disease progression or death: 0.58; 95% CI: 0.43, 0.80; P<0.001)
  • Response rate: 59.9% for olaparib patients vs 28.8% for standard-therapy patients
  • Rate of adverse events grade 3 or higher: 36.6% in olaparib patients vs 50.5% in standard-therapy patients
  • 4.9% of olaparib patients discontinued treatment due to toxic effects vs 7.7% of standard-therapy patients