FDA Approves First Drug for BRCA-Positive Breast Cancer

January 12, 2018

The FDA has expanded the approval of the PARP inhibitor olaparib (Lynparza) to include the treatment of patients with metastatic breast cancer who have a mutated BRCA gene.

The US Food and Drug Administration (FDA) has expanded the approval of the PARP inhibitor olaparib (Lynparza) to include the treatment of patients with metastatic breast cancer who have a mutated BRCA gene. Olaparib was previously approved for the treatment of BRCA-positive ovarian cancer. The drug is now approved for use in HER2-negative breast cancer patients who have been previously treated with chemotherapy in either the neoadjuvant or adjuvant setting, or for metastatic disease.

“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, in a press release. “This approval demonstrates the current paradigm of developing drugs that target the underlying genetic causes of a cancer, often across cancer types.”

The approval for this indication was based on data from the multi-center, open-label OlympiAD trial. This clinical trial included 302 patients randomized (2:1) to either 300-mg oral olaparib twice daily (n = 167) or physician’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine; n = 66). All patients had HER2-negative metastatic breast cancer, carried a germline BRCA mutation, and had received prior chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Randomization was stratified by prior use of platinum-based chemotherapy, prior use of chemotherapy for metastatic disease, and hormone-receptor status. The primary endpoint of the trial was progression-free survival.

The estimated median progression-free survival by blinded independent central review was 7 months with olaparib vs 4.2 months with chemotherapy (hazard ratio, 0.58; 95% CI, 0.43–0.80; P = .0009). Patients with measurable disease in the olaparib arm experienced an objective response rate of 52% (95% CI, 44%–60%) compared with 23% in the chemotherapy arm (95% CI, 13%–35%). The rate of complete response was also improved with olaparib (7.8% vs 1.5% with chemotherapy).

“Patients diagnosed with BRCA-related metastatic breast cancer are often younger than other breast cancer patients, and their disease is often much more aggressive and difficult to treat,” said Susan M. Domchek, MD, executive director of the Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania, and a national leader on the OlympiAD trials, in a press release. “While there is currently no cure for metastatic breast cancer, today’s approval offers a new, targeted option that may help to delay disease progression for these patients.”

The most common adverse events (> 20% of patients) in the olaparib arm included nausea (58%), anemia (40%), fatigue (including asthenia, 37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%). The rate of treatment discontinuation with olaparib was 5% vs 8% with chemotherapy.

The FDA has also granted marketing authorization for the BRACAnalysis CDx test to identify breast cancer patients with germline BRCA mutations. The effectiveness of this test was established in the OlympiAD trial population.