The U.S. Food and Drug Administration (FDA) has accepted GSK‘s request to extend approval for Zejula (niraparib) to include as a first-line maintenance therapy for women with newly diagnosed and advanced ovarian cancer who responded to platinum-based chemotherapy, regardless of mutations in DNA repair genes.
The application, made in the form of a supplemental New Drug Application (sNDA), is being reviewed under the Real-Time Oncology Review (RTOR) pilot program, set to speed up the review process and ensure that safe treatments are available as soon as possible, GSK announced in a press release.
Zejula is an oral, once-daily PARP inhibitor. It works by preventing the activity of PARP enzymes, which are involved in DNA repair. Interfering with the ability of cancer cells to repair DNA can kill these cells.
Zejula is currently approved in the United States and Europe as a maintenance therapy for patients with recurrent and high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are completely or partially responsive to platinum-based chemotherapy (usually cisplatin or carboplatin).
The FDA also approved Zejula as a late-line therapy for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer previously treated with three or more chemotherapy regimens, and whose tumors are positive for homologous recombination deficiency (HRD). That is, mutations in certain genes that hamper efficient DNA repair.
The company’s application was based on promising results from the Phase 3 PRIMA trial (PRIMA/ENGOTOV26/GOG-3012; NCT02655016).
This trial evaluated Zejula’s effectiveness and safety as a maintenance therapy in 733 women with newly diagnosed advanced cancer of the ovary, peritoneum, or fallopian tube, with or without BRCA mutations. All had responded to first-line platinum-based chemotherapy and were at high risk for relapse.
Within 12 weeks of completing the last dose of chemotherapy, these women were randomized to either 300 mg of Zejula (487 patients) or placebo (246 patients), given once daily in 28-day cycles for 36 months or until disease progression.
About half the patients (51%) had tumors positive for homologous recombination deficiency, as measured by Myriad‘s myChoice test. HDR is used to identify patients most likely to benefit from certain cancer therapies like PARP inhibitors.
Of note, myChoice is under review by the FDA for approval as a test to identify advanced ovarian cancer patients more likely to benefit from treatment with Zejula after responding to first-line platinum-based chemotherapy.
Results showed that patients in the overall population treated with Zejula lived significantly longer and with no signs of disease progression (progression-free survival, PFS) compared to similar patients given a placebo — a median of 13.8 months versus 8.2 months. This meant that those taking Zejula were 38% less likely to experience disease progression or die.
The survival benefit was even greater among patients who had HRD-positive tumors (including those who had BRCA mutations), a median PFS of 21.9 months with Zejula versus 10.4 months with a placebo. This corresponded to a 57% reduction in the risk of disease progression or death.
The most common treatment side effects graded as severe or worse were low red blood cell counts (31.0%), low platelet counts (28.7%), and low levels of neutrophils (a type of white blood cell, 12.8%). No treatment-related deaths occurred.
The results of the PRIMA trial were recently published in the journal New England Journal of Medicine in a study titled, “Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.”