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by Piri Welcsh, PhD
Based on the results of this study, today, the FDA announced the approval of Niraparib (Zejula) for adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. Zejula was approved for all patients who fit the above criteria, regardless of BRCA mutation status.
A potential breakthrough for patients with ovarian cancer was recently reported. The results described in “Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer” will likely impact treatment for ovarian cancer patients with inherited mutations in BRCA genes, but they may also apply to the larger group of women with ovarian cancer who do not have a BRCA gene mutation.
Niraparib, a PARP Inhibitor, is a type of “targeted therapy.” PARP inhibitors were developed to target the unique behavior of cancers caused by a BRCA mutation. Currently, two PARP inhibitors have been approved by the U.S. Food and Drug Administration (FDA).
The goal of this study was to determine if niraparib, given as “maintenance therapy” after treatment for ovarian cancer, increased progression-free survival—the length of time survived without cancer getting worse—for women with and without a BRCA mutation.
All of the 553 enrolled patients had platinum-sensitive, recurrent ovarian cancer. Of these, 203 had inherited a mutation in either BRCA1 or BRCA2. The other 350 enrolled ovarian cancer patients had no known inherited BRCA mutation and had high-grade serous, the most common sub-type of ovarian cancer. All patients completed treatment for their recurrence with platinum chemotherapy and were randomly assigned to receive niraparib or a placebo for “maintenance.” The goal of maintenance therapy is to extend the length of time before a new recurrence emerges or even to turn a temporary remission into a long-term cure. The trial was stopped for each patient (end-point) when her ovarian cancer progressed.
Overall, the results of this trial suggest that for those ovarian cancer patients whose cancers remain sensitive to chemotherapy, niraparib considerably extends the interval until recurrence compared to placebo. Researchers compared the response of three different groups in the study:
Some of the common side effects of taking niraparib include nausea, fatigue, constipation, vomiting, a decrease in the number of red blood cells (anemia), and a decrease in blood cells. These side effects were managed by reducing the dose of niraparib. About two-thirds of study patients required a reduced dose of niraparib due to side effects. Patients on niraparib reported a similar overall quality of life comparable to those on placebo.
The results of the niraparib trial are important for ovarian cancer patients because they suggest a benefit for “maintenance therapy” to lower the risk for recurrence after completion of chemotherapy. The addition of niraparib to the treatment of high-grade serous ovarian cancer would likely be meaningful to patients, as they often live with a fear of ovarian cancer recurrence after ending chemotherapy. However, it is important to know that we do not yet know the effect niraparib has on overall survival. At the time the trial ended, niraparib had reduced the risk of death by 27% versus placebo; however, it is too early to know if that impact is real.
In summary, this study provides important new findings that can change how we treat ovarian cancer.
The company that makes niraparib completed its submission to the FDA in November 2016. The application had already won the FDA's “priority” review status, giving it a speedier path through the agency. The FDA decision on niraparib is due June 30, 2017. If approved, niraparib will likely be approved for use after second-line chemotherapy in ovarian cancer patients.
Mirza MR, Monk BJ, Herrstedt J, et al. “Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer.” New England Journal of Medicine; December 2016; 375(22):2154-64.