HER2-negative metastatic breast cancer with a germline BRCA1/2 mutation
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Olaparib | 300 mg twice daily | Oral | Continuous |
Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation
Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, et al. N Engl J Med. 2017. 377:523-533
- Study type
- Clinical trial
- Study name
- OlympiAD
- Phase
- Phase 3
- Design
- Randomised, open-label phase 3 trial with 2:1 randomisation
- Sample size
- 302 patients (205 in the olaparib group and 97 in the standard-therapy group)
- Source
- N Engl J Med · 2017
- Trial registration
- NCT02000622
In plain words
In this study, patients with advanced (metastatic) HER2-negative breast cancer who carried an inherited mutation in a BRCA gene received either olaparib tablets or usual chemotherapy. Olaparib tablets kept the disease from progressing for longer on average (7.0 months vs 4.2 months) and shrank the tumour in more patients. Severe side effects were less common in the olaparib group than in the chemotherapy group.
Key results
7.0 months vs 4.2 months (olaparib vs standard therapy)
Median PFS (median progression-free survival)
HR for progression or death 0.58; 95% CI: 0.43 to 0.80; P<0.001
59.9% vs 28.8%
Response rate
Olaparib vs standard therapy
42%
Reduction in risk of disease progression or death
With olaparib; 2.8-month improvement in median PFS
Dose and schedule cards
Olaparib in metastatic disease (OlympiAD)
HER2-negative metastatic breast cancer with a germline BRCA1/2 mutationCycle length: ContinuousOn the page “Breast cancer” · Advanced triple-negative disease or disease with a germline BRCA mutation
Metastatic HER2-negative breast cancer with a germline BRCA mutation (OlympiAD)
After chemotherapy; in HR-positive disease after endocrine therapy or if unsuitable for itCycle length: ContinuousOn the page “Olaparib (Lynparza)” · Standard dosing (FDA label)
After chemotherapy; in HR-positive disease after endocrine therapy or if unsuitable for it
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Olaparib | 300 mg | Oral (with or without food) | Twice daily (about every 12 hours) |
On the page “Olaparib (Lynparza)” · Standard dosing (FDA label)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Treatment arms and regimens
1Olaparib group
Single-agent olaparib tablets, 300 mg orally twice daily, until progression or unacceptable toxicity.
2Standard-therapy group
Single-agent chemotherapy of physician's choice (capecitabine, eribulin or vinorelbine) at standard doses in 21-day cycles, until progression or unacceptable toxicity; the exact dose of each drug is not stated in the sources reviewed (label and trial registry).
Source of the regimen details: Abstract of the paper, FDA label for Lynparza (section 14; chemotherapy "at standard doses") and ClinicalTrials.gov NCT02000622
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with HER2-negative metastatic breast cancer and a germline BRCA mutation who had received no more than two previous chemotherapy regimens for metastatic disease; previous treatment with an anthracycline (unless contraindicated) and a taxane in any setting was required; in HR-positive disease, progression on at least one endocrine therapy or unsuitability for it; if previously treated with platinum, no progression during it; previous PARP inhibitor use was not allowed.
Endpoints
Primary endpoint: progression-free survival (PFS), assessed by blinded independent central review and analysed by intention to treat. Response rate and adverse events were also reported.
Safety and side effects
Grade 3 or higher adverse events occurred in 36.6% of the olaparib group and 50.5% of the standard-therapy group. Treatment discontinuation because of toxic effects occurred in 4.9% and 7.7% of patients, respectively.
Clinical significance and place in guidelines
This trial showed that single-agent olaparib can be a more effective option than standard single-agent chemotherapy in terms of progression-free survival and response rate in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation. This finding shows the importance of assessing germline BRCA mutation status in these patients. The status of drug approvals and clinical guideline recommendations should be checked separately, as they are not mentioned in the abstract.
Limitations
Based on the abstract, the trial was open-label. The primary endpoint was progression-free survival, assessed by blinded independent central review. The study was funded by AstraZeneca. Other limitations should be checked in the full text of the paper.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.