Richard Pazdur, MD
The FDA has approved the PARP inhibitor olaparib (Lynparza) for the treatment of women with BRCA-positive advanced ovarian cancer following treatment with three or more prior lines of chemotherapy. Along with the drug, the FDA also approved a molecular companion diagnostic test, BRACAnalysis CDx, developed by Myriad Genetics, Inc.,Â to detect the presence of BRCA
mutationsÂ in blood samples.
The accelerated approval for olaparib was based on a 34% objective response rate (ORR) seen in 137 patients withÂ BRCA
-positive ovarian cancer who had received at leastÂ three lines of chemotherapy in a single-arm phase II study.
“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 late June, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted 11-2 against the approval of the drug as maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer with germline BRCA
mutations. Following this vote, the drug's manufacturer, AstraZeneca, submitted an amendment to olaparib’s new drug application upon the FDA’s request, which led to the eventual approval.
In the pivotal single-arm phase II study, olaparib at 400 mg twice daily was administered to 137 patients with measurable germline BRCA-mutated ovarian cancer following three or more lines of prior chemotherapy. The median age of patients was 58 years and 94% were Caucasian. ORRÂ and duration of response were assessed by RECIST v1.1.
The ORR was 34%, with a 7.9-monthÂ duration of response. TheÂ complete response rate was 2%, according to the FDA's review of the data. In a larger cohort of patients with ovarian cancer (n = 178) reported in the Journal of Clinical Oncology,1
the median progression-free survival was 7 months and 54.6% of patients were free of progression at 6 months. The median overall survival was 16.6 months, with 64.4% of patients alive at 12 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 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.Â Serious AEs included the development of myelodysplastic syndrome, acute myeloid leukemia, and lung inflammation.BRCA
mutation status was verified retrospectively in 97% (59/61) of the patients with available blood samples from the phase II study using the BRACAnalysis CDx test. This data was the basis for the approval of the BRACAnalysis companion diagnostic.
"Myriad is excited to offer the first and only FDA-approved companion diagnostic for Lynparza, which we believe opens a new door in personalized medicine and represents a big step forward in tailoring treatment for women with ovarian cancer," Mark Capone, president, Myriad Genetic Laboratories, said in a statement. "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."
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.
Olaparib will be distributed exclusively through the specialty pharmacy Biologics, Inc. Prescriptions can be submitted by phone (800.850.4306), fax (800.823.4506) or eScribe, using an EMR system (NCPDP: 3430369; NPI: 1487640314).
“We are thrilled to be the exclusive provider for this groundbreaking therapy,” Dan Duffy, chief business development officer at Biologics, said in a statement. “We are honored to be a part of this important launch for AstraZeneca, and look forward to helping support patients in need of this important therapy.”
Kaufman B, Shapira-Frommer R, Schmultzler RK et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation [published online November 3, 2014]. J Clin Oncol.Â doi:10.1200/JCO.2014.56.2728.