FDA Approval Summary: Niraparib for the Maintenance Treatment of Patients with Recurrent Ovarian Cancer in Response to Platinum-Based Chemotherapy

Abstract

The FDA approved niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline mutation status (gm vs. non-gm). Progression-free survival (PFS) in each cohort was the primary endpoint. In the gm cohort, estimated median PFS on niraparib was 21 months versus 5.5 months on placebo [HR, 0.26; 95% confidence interval (CI), 0.17-0.41; < 0.0001]. In the non-gm cohort, estimated median PFS for niraparib and placebo was 9.3 and 3.9 months, respectively (HR, 0.45; 95% CI, 0.34-0.61; < 0.0001). Common adverse reactions (>20% and higher incidence in the niraparib arm) with niraparib included thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, mucositis, fatigue, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash, and hypertension. There were five cases of myelodysplastic syndrome and acute myeloid leukemia (1.4%) in patients treated with niraparib compared with two cases (1.1%) on placebo. Niraparib is the first PARP inhibitor approved as maintenance therapy for patients with ovarian, fallopian tube, or primary peritoneal cancer, with improvement in PFS, regardless of gm status. .

Pharmacological ascorbate induces ‘BRCAness’ and enhances the effects of Poly(ADP‑Ribose) polymerase inhibitors against BRCA1/2 wild‑type ovarian cancer

“…Currently, three PARPis are used as standard treatment for EOC, and two of these, olaparib and rucaparib, are used for treatment of recurrent BRCA mutant ovarian cancer, as well as maintenance therapy in platinum-sensitive relapsed EOC regardless of BRCA or HRD status (36,37). Niraparib, the third clinically used PARPi, is indicated for maintenance, and used irrespective of BRCA status (38). There is an unmet clinical need to decrease the resistance and enhance the efficacy of PARPis.…”

Mutations of BRCA2 in canine mammary tumors and their targeting potential in clinical therapy

“…Sixty-three percent of the patients with mutations experienced a clinical benefit, thus showing the clinical effect of synthetic lethality using PARPi [61]. This was further confirmed with phase II trials [62][63][64] and as a consequence, olaparib was recently approved for ovarian cancer [65], followed by other PARPi such as rucaparib, niraparib and talazoparib [66][67][68]. Unfortunately, as with other targeted therapies, acquired resistance to PARPi therapy is observed in most patients with advanced cancer [24].…”

Cancer Genetics and Therapeutic Opportunities in Urologic Practice

“…Mutations in BRCA1/2 and ATM can be targeted with PARP inhibitors. There are currently four FDA-approved PARP inhibitors (olaparib, rucaparib, niraparib, talazoparib) for other gBRCAm cancers including ovarian and breast [60][61][62][63][64][65]. These drugs have shown significant survival advantages in gBRCAm patients and previous approvals in other tumor histologies have served as the scientific basis for the currently ongoing PARPi trials in prostate cancer [66,67].…”