The Food and Drug Administration has approved niraparib, a poly ADP-ribose polymerase (PARP) inhibitor, for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
The indication does not require a suspected or confirmed deleterious BRCA mutation.
Approval was based on an improvement in progression-free survival (PFS) in the phase III NOVA trial of 553 patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received at least two prior treatments of platinum-based chemotherapy and were in a complete or partial response to the most recent chemotherapy treatment.
Median PFS in women with germline BRCA mutations who received niraparib was 21 months, compared with 5.5 months for those on placebo (hazard ratio, 0.26; 95% confidence interval: 0.17-0.41; P less than .0001), according to a study presented at the 2016 European Society for Medical Oncology Congress and published simultaneously in the New England Journal of Medicine.
Among patients who did not have a germline BRCA mutation, median PFS for patients on niraparib was 9.3 months, compared with 3.9 months for those on placebo (HR, 0.45; 95% CI, 0.34-0.61; P less than .0001).
Patients enrolled in NOVA were randomized (2:1) within 8 weeks of the last therapy to either niraparib (300 mg orally daily) or matched placebo. Patients were assigned to one of two cohorts based on the BRACAnalysis CDx . Patients with deleterious or suspected deleterious germline BRCA mutations were assigned to the germline BRCA-mutated cohort (n = 203), and those without germline BRCA mutations were assigned to the nonmutated cohort (n = 350).
Niraparib’s safety was evaluated in 367 patients with platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancer in the NOVA trial, according to a statement from the FDA.
The most common adverse reactions were thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and hypertension.
Myelodysplastic syndrome and/or acute myeloid leukemia occurred in 5 of 367 (1.4%) patients receiving niraparib and in 2 of 179 (1.1%) patients assigned to placebo. Grade 3-4 hypertension occurred in 9% of niraparib-treated patients, compared with 2% of patients assigned to placebo, according to the FDA.
Niraparib is the third PARP inhibitor to receive approval for ovarian cancer, following approval of olaparib (Lynparza) for patients with advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy and whose tumors have a deleterious BRCA mutation as detected by an FDA-approved test and accelerated approval of rucaparib (Rubraca) for women with advanced ovarian cancer who have been treated with two or more chemotherapies and whose tumors have a deleterious BRCA mutation as identified by an FDA-approved companion diagnostic test.
The recommended dose and schedule of niraparib is 300 mg taken once daily with or without food.
Full prescribing information is available here .
Niraparib is being marketed as Zejula by Tesaro. Following FDA announcement of the approval, Tesaro announced an expanded development program for niraparib focused on the treatment of front-line metastatic ovarian and lung cancers and metastatic breast cancer.
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