The FDA has approved the PARP inhibitor olaparib (Lynparza) for the treatment of women with BRCA-positive advanced ovarian cancer.
Richard Pazdur, MD
AstraZeneca, the company developing the drug
The FDA has approved the PARP inhibitor olaparib (Lynparza) for the treatment of women with BRCA-positive advanced ovarian cancer. The approval was based on results from a single-arm phase II study of patients with deleterious or suspected deleterious germline BRCA-mutated advanced cancers,1according to.
Along with the drug, the FDA also approved a molecular companion diagnostic test, BRACAnalysis CDx, developed by Myriad Genetics, Inc., to detect the presence of mutations in BRCA genes in blood samples.
“Today’s approval constitutes the first of a new class of drugs for treating ovarian cancer,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in a statement. “Lynparza 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.”
In June 2014, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 11-2 against the approval of the agent as maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer with germlineBRCAmutations.2In July, AstraZeneca submitted an amendment to olaparib’s new drug application upon the FDA’s request.
AstraZeneca, was based on
Olaparib's efficacy, according toan analysis of 137 patients withBRCA-positive ovarian cancer who had received at least three lines of chemotherapy. In this analysis, 34% of patients achieved an objective response for an average of 7.9 months.
“The FDA approval of Lynparza is a significant milestone for our patients as currently there are only limited treatment options available to women with ovarian cancer who carry the BRCA mutation,” Ursula A. Matulonis, MD, associate professor of medicine, Harvard Medical School, director, Gynecological Oncology Program, Dana-Farber Cancer Institute, said in a statement.
The efficacy of BRACAnalysis CDx was validated using blood samples from patients on the same trial that was the basis of olaparib's approval.
"Less than 25% of ovarian cancer patients know their germline BRCA status, which is critical for any ovarian cancer patient who may be considered for treatment with Lynparza,” Mark Capone, president, Myriad Genetic Laboratories, said in a statement.
The most commonly reported adverse events associated with olaparib included nausea, fatigue, vomiting, diarrhea, dysgeusia, dyspepsia, headache, decreased appetite, nasopharyngitis, cough, arthralgia, musculoskeletal pain, myalgia, back pain, dermatitis, and abdominal pain. Serious AEs included the development of myelodysplastic syndrome, acute myeloid leukemia, and lung inflammation.
An FDA review of either of the phase III SOLO2 or SOLO3 trial could lead to a full approval of olaparib in ovarian cancer. SOLO2 is comparing the agent to placebo as maintenance therapy, while SOLO3 is comparing the agent to standard chemotherapy for relapsed disease.