Lynparza (olaparib tablets), a poly ADP-ribose polymerase inhibitor, is now approved to treat inherited BRCA-mutated, human epidermal growth factor receptor 2-negative metastatic breast cancer in patients who were previously treated with chemotherapy. Hormone receptor-positive breast cancer patients who are candidates for Lynparza should have been previously treated with endocrine therapy or been considered inappropriate for endocrine treatment. Before receiving Lynparza, patients must be given a Food and Drug Administration-approved genetic test-the BRACAnalysis CDx-to determine they have the BRCA genetic mutation.
Lynparza is the first drug in its class to be approved to treat breast cancer, and its approval marks the first time any drug has been approved to treat BRCA-mutated breast cancer. Lynparza was previously approved for the treatment of BRCA-mutated ovarian cancer. The approval of Lynparza for breast cancer highlights a shift in cancer drug development to develop drugs that target the underlying genetic causes of a cancer.
Because Lynparza is primarily metabolized by an isoenzyme in the cytochrome P-450 (CYP) enzyme system, CYP3A, drugs that are strong or moderate inhibitors of this isoenzyme should be avoided, if possible, as they will greatly increase circulating levels of Lynparza (by between 121% and 170%). If coadministration cannot be avoided, then the Lynparza dose should be decreased. Grapefruit and Seville oranges (and their juices) are also CYP3A inhibitors and will increase circulating levels of Lynparza. Drugs that are strong or moderate CYP3A inducers will decrease plasma concentrations of Lynparza (by 60% to 87%) and should also be avoided. (See Table 1 for a list of strong and moderate CYP3A inhibitors and inducers.)
The most common adverse effects of Lynparza, occurring in 20% or more of patients taking the drug, include anemia, nausea, fatigue and weakness, vomiting, neutropenia, leukopenia, nasopharyngitis/upper respiratory tract infections or influenza, respiratory tract infections, diarrhea, arthralgia/myalgia, distorted sense of taste, decreased appetite, constipation, and stomatitis. Less common adverse effects include myelodysplastic syndrome/acute myeloid leukemia, pneumonitis, and embryo-fetal toxicity. Laboratory values can also be affected by Lynparza therapy. The most common of these adverse effects, occurring in 25% or more of those receiving the drug, include decreased hemoglobin, increased mean corpuscular volume, decreased lymphocytes, decreased leukocytes, decreased absolute neutrophil count, increased serum creatinine, and decreased platelets.
Nurses need to carefully check the label on the drug container against the prescribing information to prevent a dosing error. Lynparza tablets should be used, and should not be substituted with Lynparza capsules on a milligram per milligram basis. The bioavailability of the medication is higher in the tablet formulation. Lynparza tablets should be taken orally twice daily, with or without food.
To prevent serious, potentially fatal adverse effects, the nurse should monitor the patient at baseline and once a month during therapy for hematologic toxicity and pneumonitis, and consult with the prescriber about discontinuing Lynparza if either are confirmed. Patients should be advised to use effective contraception during Lynparza treatment and for three months after the last dose. Nurses should educate patients taking Lynparza on the drug's possible adverse effects, and should also teach patients to review the drug's label each time they fill a prescription as it will contain the most up-to-date information about adverse effects. For full prescribing information for Lynparza, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208558s001lbl.pdf.