Niraparib (Zejula, Tesaro) has been approved by the US Food and Drug Administration (FDA) for use in the maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy.
Niraparib is a poly ADP-ribose polymerase (PARP) inhibitor, but unlike other drugs in this class, it is active both in patients with and those without BRCA mutations.
Another PARP inhibitor, olaparib (Lynparza, AstraZeneca), is restricted for use in patients with ovarian cancer who carry the BRCA mutation, which amounts to 15% to 20% of the patient population.
The approval is based on results from the phase 3 trial known as NOVA, which showed a significant improvement in progression-free survival (PFS) with niraparib compared to placebo.
These results were reported by Medscape Medical News last year when they were presented at the 2016 European Society for Medical Oncology (ESMO) Congress and were simultaneously published in the New England Journal of Medicine.
"This is a breakthrough for patients with ovarian cancer," lead investigator Mansoor Mirza, MD, chief oncologist, Department of Oncology, Copenhagen University Hospital-Rigshospitalet, Denmark, said at the time.
"We have never seen such large benefits in PFS in recurrent ovarian cancer. Niraparib significantly improved all endpoints across a broad patient population, representing 70% of all ovarian cancer patients. These landmark results could change the way we treat this disease," he added.
The trial was conducted in 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. Within 8 weeks of their last therapy, patients were randomly allocated in a 2:1 ratio to receive either niraparib 300 mg orally daily or matched placebo.
This is also the dose that has been approved – niraparib 300 mg, taken once daily with or without food.
Patients in the NOVA trial were divided into two groups – those with germline BRCA mutation (n = 203) and those without (n = 350).
The results showed a significant improvement in PFS in both cohorts.
In the patients with a germline BRCA mutation, the estimated median PFS for those taking niraparib was 21 months compared with 5.5 months for those taking placebo (hazard ratio [HR] = 0.26; P < .0001).
In patients without a mutation, the estimated median PFS for those taking niraparib was 9.3 months compared with 3.9 months for those taking placebo (HR = 0.45; P < .0001).
"Significant Step Forward"
Discussing these results at the ESMO meeting, Sandro Pignata, MD, PhD, director, Instituto Nazionale Tumori, IRCCS Fondazione Pascale, Napoli, Italy, described the findings as a "significant step forward in the treatment of ovarian cancer."
He said that the "main novelty" of the study in comparison with previous investigations with PARP inhibitors was that non-germline-mutation patients were included along with HRD-positive individuals.
For Dr Pignata, niraparib achieved "extraordinary results" in patients with BRCA mutations "that modified the clinical history of these patients," and the patient subgroups experienced significant benefits. He said that overall, he feels these results will change the treatment of ovarian cancer and that we are ready to "move beyond" BRCA mutation for determining therapeutic choices.
Nevertheless, Dr Pignata asked, "Who are these patients who are responding to niraparib?" He noted that all patients were selected for being highly sensitive to platinum, "which is the main clinical parameter for selecting PARP inhibitors," and questions remain as to why the different subgroups responded to treatment.
He added that it is important to note that a number of patients in the current study remained on treatment at 18 months, which has also been seen in trials of olaparib. "So, we have to concluded that there are many exceptional responders" to PARP inhibitors, he said. However, the across-the-board responses among subgroups means it is currently not possible to determine who will will have a long-term response.
The FDA notes that niraparib's safety was evaluated in 367 patients with platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancer in the NOVA trial. The most common adverse reactions occurring in at least 10% of patients receiving niraparib 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 who received niraparib and in 2 of 179 (1.1%) patients who received placebo. Grade 3-4 hypertension occurred in 9% of niraparib-treated patients compared with 2% of patients who received placebo.
Full prescribing information is available online.
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Cite this: Niraparib Approved for Ovarian Cancer Maintenance Tx - Medscape - Mar 27, 2017.