The Food and Drug Administration (FDA) has approved olaparib (Lynparza) for the adjuvant treatment of adult patients who have, or are suspected to have, the genetic (germline) variation of BRCA-mutated human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who were previously treated with neoadjuvant or adjuvant chemotherapy. A specific FDA-approved companion diagnostic is used to determine if a patient is an appropriate candidate for the drug. Olaparib was previously approved for first-line maintenance treatment of BRCA-mutated advanced ovarian cancer, alone or with bevacizumab; for maintenance treatment of adults who have, or are suspected to have, BRCA-mutated metastatic pancreatic cancer; or for adults who have, or are suspected to have, homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed after treatment.

Olaparib is a poly ADP-ribose polymerase (PARP) inhibitor. PARP enzymes are involved in normal cellular functions, such as DNA transcription and DNA repair. By inhibiting PARP enzymes, olaparib inhibits the growth of select tumor cell lines. The drug is taken orally twice a day.

Olaparib's new approval was based on results of a randomized, double-blind, placebo-controlled, international study of 1,836 patients with BRCA-mutated HER2-negative high-risk early breast cancer who completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. The primary efficacy end point was invasive disease-free survival (from time of randomization to date of first recurrence). There were 106 events (12% of patients) in the olaparib arm compared with 178 events (20% of patients) in the placebo arm. The invasive disease-free survival rate at three years was 86% for patients receiving olaparib and 77% for those receiving placebo. The second efficacy end point was overall survival. There were 75 deaths (8%) in the olaparib arm and 109 deaths (12%) in the placebo arm. Those receiving olaparib had significantly improved efficacy outcomes compared with those receiving placebo.

The most common adverse effects in the clinical trial were nausea, fatigue, anemia, vomiting, headache, diarrhea, leukopenia, neutropenia, decreased appetite, altered taste, dizziness, and stomatitis. These adverse effects are similar to those of olaparib when the drug is used to treat other cancers. The product labeling also warns of the risk of myelodysplastic syndrome/acute myeloid leukemia, pneumonitis, and embryo-fetal toxicity from all uses of olaparib. Olaparib may also increase the risk of venous thromboembolic events, including pulmonary embolism, in patients with mCRPC.

Nurses should confirm that women of reproductive age are not pregnant prior to starting olaparib. Nurses should teach women to use effective birth control during therapy and for at least six months after stopping olaparib to prevent fetal toxicity. Women should also not breastfeed for at least one month after stopping olaparib. Men should not donate sperm during therapy and for at least three months after discontinuation of therapy.

For complete prescribing information for olaparib, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208558s023lbl.pdf.