FDA Approves Niraparib as Maintenance Therapy for Recurrent Ovarian Cancer
, by NCI Staff
UPDATE: In November 2022, the approval of niraparib as maintenance therapy for women with advanced ovarian cancer underwent an important change. The treatment can now only be prescribed for women who have, or are suspected to have, an inherited mutation (also called a “germline” mutation) in the BRCA1 or BRCA2 genes. The change was requested by FDA based on overall survival data from the trial described below.
Niraparib is one of a class of drugs known as PARP inhibitors, which work by disrupting cancer cells’ ability to repair DNA damage. The approval makes niraparib the third PARP inhibitor approved by FDA for treating ovarian cancer.
The approval covers the use of niraparib as a maintenance therapy in women who have already had a recurrence of high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer but have had a complete or partial tumor response to platinum-based chemotherapy.
Niraparib, which is taken as a pill, is approved for use whether or not patients have germline, or inherited, mutations in the BRCA1 or BRCA2 genes. (FDA changed this approval in November 2022. See the update box at the top of this page for details.)
“The development and approval of several PARP inhibitors has been an important advance in the treatment of ovarian cancer,” said Elise Kohn, M.D., head of Gynecologic Cancer Therapeutics in NCI’s Division of Cancer Treatment and Diagnosis.
And research on their use is quickly expanding to other cancers, Dr. Kohn continued, including breast, prostate, pancreatic, and gastric cancers.
“It’s the beginning of a new class of agents: the DNA repair-inhibitor class,” she said.
Treatment for Cancers with or without BRCA Mutations
This is the first FDA approval for niraparib. It was approved based on a randomized trial of more than 550 patients who had already experienced a recurrence of their high-grade serous ovarian, fallopian tube, or primary peritoneal cancer.
All patients in the trial had undergone at least two courses of treatment with platinum-based chemotherapy and their cancer had responded completely or partially to the most recent treatment. Patients were randomly assigned to receive niraparib or a placebo. The primary endpoint was the length of time patients lived without their disease progressing.
The trial included two cohorts of women: those with and without germline BRCA mutations. Among women who had germline BRCA mutations, those who received niraparib had a median progression-free survival of 21 months, compared with 5.5 months for women who received placebo. Among women without BRCA mutations, median progression-free survival was 9.3 months for those who received niraparib and 3.9 months for those who received the placebo.
Some of the most common side effects for patients who received niraparib were anemia, palpitations, nausea, and fatigue. The drug carries risks of some serious side effects, including the development of myelodysplastic syndrome and acute myeloid leukemia.
The results of this trial, which were originally published last year in the New England Journal of Medicine, focus on progression-free survival, cautioned Dr. Kohn. “We don’t know if niraparib maintenance treatment in this setting will prolong overall survival. We’ll have to wait for the maturation of these data.”
Women with platinum-sensitive recurrent ovarian cancer often go on to receive numerous other treatment regimens during the course of their disease, Dr. Kohn continued, which can make it difficult to pinpoint the effect of one treatment on overall survival.
Next Steps in Research
Because PARP inhibitors block cancer cells from repairing damaged DNA, they have been shown to be especially effective against cancer cells that already have defective DNA repair mechanisms, such as those with BRCA mutations.
The two other FDA-approved PARP inhibitors, olaparib (Lynparza®) and rucaparib (Rubraca™), have been approved for patients with advanced disease who have been previously treated with at least three and two chemotherapy regimens, respectively.
But both drugs are approved as treatment rather than maintenance therapy, and for women with deleterious germline BRCA mutations. Rucaparib is also approved for women with deleterious somatic, or noninherited, BRCA mutations. The FDA granted olaparib priority review for use as a maintenance therapy last month.
Dr. Kohn said key questions for additional research include identifying biomarkers that may predict who is most likely to benefit from PARP inhibitors or other DNA-repair inhibitors, potentially effective drugs to use in combination with PARP inhibitors, mechanisms of resistance, and how these mechanisms can be overcome.
“These questions may apply to ovarian cancer now,” she added. “But as further indications are identified for this new class of agents, they’ll also apply to other cancers.”