LYNPARZA™ (olaparib) Approval: First in Class for Patients With Advanced Ovarian Cancer and a BRCA Mutation
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After an expedited review process, at the end of 2014 the US Food and Drug Administration (FDA) granted accelerated approval to LYNPARZA™ (olaparib). Olaparib is the first-in-class monotherapy for patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with at least 3 prior lines of chemotherapy. Olaparib inhibits poly (ADP-ribose) polymerase (PARP) enzymes, which in turn inhibit the growth of select tumor cells and decrease tumor growth in human cancer. This decision is surprising because earlier in 2014 the Oncologic Drugs Advisory Committee (ODAC) of the FDA voted 11 to 2 against the approval of olaparib as maintenance therapy against the recurrence of ovarian cancer. After the ODAC vote, however, the manufacturer of olaparib presented additional data to the FDA supporting its use in BRCA-mutated cancer based on a single-group open-label trial of 137 patients with BRCA-mutated ovarian cancer who had already undergone at least 3 courses of chemotherapy.
Under the premarket approval pathway for high-risk medical devices the FDA also approved the BRACAnalysis Companion Diagnostic (CDx) device, use of which is required in conjunction with olaparib. This CDx device detects and classifies mutations in BRCA1 and BRCA2 genes in blood samples of patients with ovarian cancer. Normal functioning BRCA genes are involved in DNA repair and work to suppress tumor growth; however, an estimated 10% to 15% of patients with ovarian cancer harbor BRCA mutations and less than 25% of patients with ovarian cancer are aware of their BRCA status. Previously, the BRACAnalysis CDx device had been sold as a laboratory developed test not specifically for the determination of BRCA status. However, with FDA approval, the device is now specifically indicated for use in determining olaparib-eligible candidates.
Approvals of olaparib and the BRACAnalysis CDx device were based on the same trial in 137 patients with ovarian cancer and the BRCA mutation, all of whom received olaparib. The study measured the objective response rate (ORR), or the percentage of patients with shrinkage or complete disappearance of the tumor. Results demonstrated that 34% of patients experienced an overall response for an average of 7.9 months. Serious adverse effects can be associated with olaparib therapy, including the development of myelodysplastic syndrome or acute myeloid leukemia (2% incidence in the 137-patient trial), and lung inflammation. Adverse effects most commonly associated with olaparib include nausea, fatigue, vomiting, diarrhea, distorted taste (dysgeusia), dyspepsia, headache, decreased appetite, nasopharyngitis, cough, arthralgia, musculoskeletal pain, myalgia, back pain, dermatitis, and abdominal pain.
Contributed by William Yarnall, RPh, CCP Medical Writer, Connexion Healthcare