On January 12, 2018, the U.S. Food and Drug Administration (FDA) granted regular approval to olaparib (Lynparza), a poly ADP-ribose polymerase (PARP) inhibitor, for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative metastatic breast cancer who have been treated with chemotherapy in either the neoadjuvant, adjuvant, or metastatic setting.
This is the first FDA-approved treatment for patients with germline BRCA-mutated, HER2-negative metastatic breast cancer. Patients with hormone receptor–positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine treatment. Patients must be selected for therapy based on the FDA-approved companion diagnostic for olaparib, BRACAnalysis CDx.
Richard Pazdur, MD
“This class of drugs has been used to treat advanced, BRCA-mutated ovarian cancer and has now shown efficacy in treating certain types of BRCA-mutated breast cancer,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”
Approval was based on data from the OlympiAD trial, an open-label, multicenter clinical trial that randomized 302 patients with germline BRCA-mutated, HER2-negative metastatic breast cancer (2:1) to olaparib at 300 mg orally twice daily or physician’s choice of chemotherapy (capecitabine, vinorelbine, or eribulin [Halaven]). All patients had to have a known deleterious or suspected deleterious germline BRCA mutation and must have received prior chemotherapy in the neoadjuvant, adjuvant, or metastatic setting to be randomized. Randomization was stratified by prior use of chemotherapy for metastatic disease; hormone receptor status (hormone receptor–positive vs triple-negative); and previous use of platinum-based chemotherapy.
The primary efficacy outcome was progression-free survival assessed by blinded independent central review. Estimated median progression-free survival was 7.0 and 4.2 months in the olaparib and chemotherapy arms, respectively (hazard ratio = 0.58, 95% confidence interval = 0.43–0.80; P = .0009).
The most common adverse reactions reported in at least 20% of patients taking olaparib in clinical trials were anemia, nausea, fatigue (including asthenia), vomiting, neutropenia, leukopenia, nasopharyngitis/upper respiratory tract infection/influenza, respiratory tract infection, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis.
About the BRACAnalysis CDx Test
The FDA also granted marketing authorization for the BRACAnalysis CDx test for use as an aid in identifying patients with breast cancer with deleterious or suspected deleterious germline BRCA-mutation who may be eligible for olaparib. The effectiveness of the BRACAnalysis CDx test was established based on the OlympiAD trial population, for whom deleterious or suspected deleterious germline BRCA-mutated status was confirmed with prospective or retrospective testing with the BRACAnalysis CDx test.
The recommended dose of olaparib is 300 mg (two 150 mg tablets) taken orally twice daily with or without food.
The FDA granted the approval of olaparib to AstraZeneca Pharmaceuticals LP. The approval of the BRACAnalysis CDx was granted to Myriad Genetic Laboratories, Inc. Visit FDA.gov for more information. ■