Olaparib Maintenance Therapy in Metastatic Breast Cancer

Exclusion Criteria

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• •1. Cytotoxic chemotherapy, hormonal or non hormonal targeted therapy within 21 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 21 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 5 days prior to study treatment.
• •2. More than 2 prior lines of cytotoxic chemotherapy for metastatic disease.
• •1. Prior treatments with hormonal therapy and non hormonal targeted therapy are allowed and not counted as a prior line of cytotoxic chemotherapy.
• •2. For the purposes of this protocol, the combination of "an aromatase inhibitor and everolimus" or "a hormonal therapy and CDK4/6 inhibitor" is not considered cytotoxic chemotherapy.
• •3. Treatment with biologics will not be considered as prior line of therapy.
• •4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• •3. Previous treatment with a PARP inhibitor (including olaparib)
• •4. The minimum washout period for immune checkpoint blockade therapy shall be 21 days.
• •5. Patients with MDS/AML or with features suggestive of MDS/AML.
• •6. Patients with second primary cancer, EXCEPTIONS: adequately treated non melanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years prior to study entry (including lymphomas \[without bone marrow involvement\]).
• •7. Mean resting corrected QTc interval using the Fridericia formula (QTcF) \>470 msec/female patients and \>450 msec for male patients (as calculated per institutional standards) obtained from 3 ECGs performed 2-5 minutes apart at study entry, or congenital long QT syndrome.
• •8. Any of the following cardiac diseases currently or within the last 6 months
• •1. Unstable angina pectoris
• •2. Congestive heart failure ≥ Class 2 as defined by the New York Heart Association
• •3. Acute myocardial infarction
• •4. Conduction abnormality not controlled with pacemaker or medication (patients with a conduction abnormality controlled with pacemaker or medication at the time of screening are eligible)
• •5. Significant ventricular or supraventricular arrhythmias (patients with chronic rate- controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
• •9. Concomitant use of known strong cytochrome P (CYP) 3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.
• •ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks.
• •Patient has had prescription or non-prescription drugs or other products known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Patients should stop using herbal medications 7 days prior to first dose of study treatment.
• •10. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. 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.
• •11. Persistent toxicities (≥ CTCAE grade 2) caused by previous cancer therapy, excluding alopecia.
• •12. Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
• •13. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• •14. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
• •a. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution CT scan or any psychiatric disorder that prohibits obtaining informed consent, and any other medical condition that, in the opinion of the Investigator, places the patient at unacceptable risk of toxicity.
• •15. Patients with symptomatic uncontrolled brain metastases.
• •1. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days.
• •2. Patients with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria: Disease outside the CNS is present. No clinical evidence of progression since completion of CNS-directed therapy. Minimum of 3 weeks between completion of radiotherapy and Cycle 1 Day 1 and recovery from significant (Grade ≥3) acute toxicity with no ongoing requirement for \>10 mg of prednisone per day or an equivalent dose of other corticosteroid. If on corticosteroids, the patient should be receiving a stable dose of corticosteroids, started at least 4 weeks prior to treatment.
• •16. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• •17. Patients with a known hypersensitivity to olaparib or any of the excipients of the products.
• •18. Pregnant or breast feeding women.
• •20. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)