At the request of the Food and Drug Administration (FDA), GlaxoSmithKline is restricting the use of Zejula® (niraparib) for second-line maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy to those with deleterious or suspected deleterious germline BRCA mutations (gBRCAmut) only.
The decision to restrict the indication follows an FDA review of the double-blind, placebo-controlled phase 3 ENGOT-OV16/NOVA trial (ClinicalTrials.gov Identifier: NCT01847274), which compared the efficacy and safety of niraparib to placebo for the maintenance treatment of women with platinum-sensitive recurrent ovarian cancer. Patients with deleterious or suspected deleterious gBRCAmut were assigned to the gBRCAmut cohort (n=203), and those without gBRCAmut were assigned to the non-gBRCAmut cohort (n=350).
While both cohorts met the primary endpoint of progression-free survival, the final overall survival (OS) analysis showed a hazard ratio of 1.06 (95% CI, 0.81-1.37) in the non-gBRCAmut cohort; median OS was 31 months for the niraparib arm and 34.8 months for the placebo arm. In the non-gBRCAmut/HRD positive status subgroup, median OS was 35.6 months for the niraparib arm and 41.4 months for the placebo arm (HR, 1.29; 95% CI, 0.85-1.95).
In the gBRCAmut cohort, median OS was reported to be 40.9 months for niraparib-treated patients vs 38.1 months for patients on placebo (HR, 0.85 [95% CI, 0.61-1.20]).
In a letter to health care providers, GlaxoSmithKline is advising prescribers not to initiate new treatment with Zejula for maintenance treatment of patients with non-gBRCAmut platinum sensitive recurrent high grade serious epithelial ovarian, fallopian tube, or primary peritoneal cancer in the second or later line setting. For patients already receiving treatment for this indication, an individual benefit-risk assessment should be conducted so that an informed decision regarding ongoing care can be made.
The first-line indication for Zejula for the maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a complete or partial response to platinum-based chemotherapy remains unchanged.
GlaxoSmithKline is currently working with the FDA on the revisions to the prescribing information for Zejula to reflect the restriction.
- GSK provides an update on Zejula (niraparib) US prescribing information. News release. GSK plc. November 11, 2022. Accessed November 15, 2022. https://www.gsk.com/en-gb/media/press-releases/gsk-provides-an-update-on-zejula-niraparib-us-prescribing-information/
- Zejula. Package insert. GSK plc; 2022. Accessed November 15, 2022. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Zejula_Capsules/pdf/ZEJULA-CAPSULES-PI-PIL.PDF
- Dear Health Care Provider Letter (Niraparib). GSK plc. Accessed November 15, 2022. https://www.zejulahcp.com/content/dam/cf-pharma/hcp-zejulahcp-v2/en_US/pdf/ZEJULA%20(niraparib)%20Dear%20HCP%20Letter%20November%202022.pdf