Lynparza First Treatment Approved for Patients with Germline BRCA-Positive Metastatic Breast Cancer

March 2018, Vol 8, No 3 - FDA News


On January 12, 2018, the FDA approved a new indication for olaparib (Lynparza; AstraZeneca) for the treatment of women with deleterious or suspected deleterious germline BRCA-positive, HER2-negative, metastatic breast cancer who received previous chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is the first FDA-approved treatment for this patient population. Like other PARP inhibitors, olaparib was previously approved for the treatment of ovarian cancer.

“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. This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.

This FDA approval was based on results from the randomized, open-label OlympiAD clinical trial of 302 patients with germline BRCA-positive, HER2-negative, metastatic breast cancer. Patients were randomized based on their previous chemotherapy for metastatic disease, hormone receptor status, and previous platinum-based chemotherapy. The primary end point was progression-free survival (PFS). The median PFS was 7 months with olaparib versus 4.2 months with chemotherapy alone (hazard ratio, 0.58; 95% confidence interval, 0.43-0.80; P = .0009).

The most common (≥20%) adverse reactions reported with olaparib were anemia, nausea, fatigue, vomiting, neutropenia, leukopenia, nasopharyngitis, influenza, respiratory tract infection, diarrhea, arthralgia, myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation, and stomatitis.

On the same day, the FDA approved the BRACAnalysis CDx test (Myriad Genetic Laboratories), which is used to identify patients with breast cancer and deleterious or suspected deleterious germline BRCA mutations who may be eligible for treatment with olaparib.