The U.S. Food and Drug Administration (FDA) has granted accelerated approval to olaparib (Lynparza) for women with advanced ovarian cancer with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer, as detected by an FDA-approved test, who have been treated with three or more prior lines of chemotherapy. The FDA concurrently approved a companion diagnostic, BRACAnalysis CDx, for the qualitative detection and classification of variants in the BRCA1 and BRCA2 genes.
Olaparib is a poly ADP-ribose polymerase (PARP) inhibitor that blocks enzymes involved in repairing DNA.
“[This] approval constitutes the first of a new class of drugs for treating ovarian cancer,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Olaparib is approved for patients with specific abnormalities in the BRCA gene and is an example of how a greater understanding of the underlying mechanisms of disease can lead to targeted, more personalized treatment.”
Clinical Trial
Olaparib’s efficacy was examined in a study of 137 participants with germline BRCA mutation–associated advanced ovarian cancer. The study was designed to measure objective response rate, and results showed that 34% of participants experienced an objective response for an average of 7.9 months.
Common side effects of olaparib included nausea, fatigue, vomiting, diarrhea, distorted taste, indigestion, headache, decreased appetite, nasopharyngitis, cough, joint pain, musculoskeletal pain, muscle pain, back pain, rash, and abdominal pain. Serious side effects included the development of myelodysplastic syndrome, acute myeloid leukemia, and lung inflammation. The most common laboratory abnormalities were increased creatinine levels, increased average volume of red blood cells, decreased hemoglobin, decreased lymphocytes and neutrophils, and decreased platelet levels.
Approval Process
In June, olaparib was reviewed by the FDA’s Oncologic Drugs Advisory Committee for potential use as maintenance therapy. The committee advised the agency in a vote of 11 to 2 that the data did not support olaparib’s accelerated approval for this use. The company then submitted additional information supporting olaparib’s use for a different indication: in patients with germline BRCA mutation–associated ovarian cancer who have received three or more chemotherapy treatments.
The FDA is approving olaparib under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. ■
