Patients will be randomised in 1:1 ratio to either olaparib or placebo. Randomisation will be
stratified by Hormone receptor status (ER and/or PgR positive/HER2 negative versus TNBC),
prior neoadjuvant versus adjuvant chemotherapy and prior platinum use for breast cancer.
Randomised patients will receive study treatment for up to a maximum of 12 months. All
patients will have safety assessments every 2 weeks during the first month, every 4 weeks for
the following 5 months and 3 monthly for the remaining 6 months of study treatment plus 30
days after its discontinuation. Following randomisation, all patients will be assessed
regularly for signs, symptoms and evidence of disease recurrence by taking medical history,
physical examination and mammogram/breast MRI. Efficacy assessments will be performed on a 3
monthly basis during the first 2 years, followed by 6 monthly assessments for years 3, 4 and
5 and annually thereafter. All patients (except those with bilateral mastectomy) will have
mammogram / breast MRI annually for 10 years beginning 6 months after randomisation.
All randomised patients will have clinical assessment visits for 10 years following their
randomisation into the study. Once a patient completes 10 years of clinical assessment they
will enter the survival follow up phase of the trial which will continue until 10 years after
the last patient is randomised.
- Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast
that is one of the following phenotypes:
1. Triple negative breast cancer defined as: ER and PgR negative AND HER2 negative
(not eligible for anti-HER2 therapy)
2. ER and/or PgR positive, HER2 negative
- Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or
suspected deleterious (known or predicted to be detrimental/lead to loss of function).
- Completed adequate breast and axilla surgery.
- Completed at least 6 cycles neoadjuvant or adjuvant chemotherapy containing
anthracyclines, taxanes or the combination of both. Prior platinum as potentially
curative treatment for prior cancer (e.g. ovarian) or as adjuvant or neoadjuvant
treatment for breast cancer is allowed.
- ECOG 0-1.
- Any previous treatment with a PARP inhibitor, including olaparib and/or known
hypersensitivity to any of the excipients of study treatment.
- Patients with second primary malignancy. EXCEPTIONS are:
1. adequately treated non-melanoma skin cancer, curatively treated in situ cancer of
the cervix, Ductal Carcinoma in situ (DCIS) of the breast, stage 1 grade 1
2. other solid tumours and lymphomas (without bone marrow involvement) diagnosed ≥ 5
years prior to randomisation and treated with no evidence of disease recurrence
and for whom no more than one line of chemotherapy was applied.
- Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.,
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
period prior to starting study treatment is 2 weeks. Concomitant use of known strong
(e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine,
carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g.,
bosentan, efavirenz, modafinil). The required washout period prior to starting study
treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
- Evidence of metastatic breast cancer