Today, the FDA approved the first PARP inhibitor for the treatment of breast cancer with a BRCA mutation. 
 
January 12, 2018—Today, the U.S. Food and Drug Administration (FDA) expanded the approval of olaparib, an oral PARP inhibitor, to include the treatment of patients with metastatic breast cancer with a BRCA mutation.
 
“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.”
 
This indication is based on results from the phase III OlympiAD trial (NCT02000622), whose results were presented at the ASCO Annual Meeting last year. A total of 205 patients were randomized to receive 300 mg of olaparib twice daily, while 97 patients received physician’s choice chemotherapy. The trial found median progression-free survival (PFS) for patients receiving olaparib was 7.0 months, compared to 4.2 months for patients receiving chemotherapy alone. An overall response rate (ORR) of 59.9% was observed in the olaparib group versus 28.8% in patients receiving standard therapy. The trial also reported that the benefits of olaparib treatment did not seem to extend to overall survival (OS) and reported no significant difference at the time of primary analysis. A full readout of the OlympiAD trial was published in The New England Journal of Medicine in August of last year.
 
Poly (ADP-ribose) polymerase (PARP) comprise a family of proteins which play a role in numerous cellular functions, including DNA transcription and repair. PARP inhibitors function by binding PARP family proteins to the sites of DNA damage, “trapping” them and thereby preventing DNA repair, replication, or transcription. This trapping of PARP to DNA induces further DNA damage, triggering cell death.
 
Olaparib was first approved in 2014 for the treatment of ovarian cancers, also with BRCA mutations. Olaparib may now be used in patients with metastatic breast cancer carrying the same mutations, who are HER2-negative and have been previously treated with chemotherapy. The FDA states that HR-positive breast cancer patients should receive prior endocrine therapy before treatment with olaparib, or otherwise be considered ineligible for endocrine treatment.
 
The FDA also expanded the approval of the BRACAnalysis CDx, an approved companion diagnostic for olaparib, to include the detection of BRCA mutations in blood samples from patients with breast cancer.
 
--
 
Jonathan A. Bell
Published Online: Friday, January 12, 2018