After review of phase 3 data, GSK will limit the use of Zejula in the second line to those with inherited BRCA mutations.
At the request of the FDA, GSK said it will restrict the second-line maintenance indication for its ovarian cancer drug Zejula (niraparib) to only the patient population with deleterious germline BRCA mutations. The FDA reviewed a recent GSK phase 3 study, which showed a hazard ratio of 1.05 in the non-germline BRCA mutations cohort in overall survival (OS) with the PARP-inhibitor Zejula, GSK said in a press release.
The FDA has canceled the upcoming meeting with the Oncologic Drugs Advisory Committee that was scheduled for Nov. 22, 2022, to discuss the phase 3 data of Zejula to treat patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer
However, the first-line indication of Zejula remains unchanged for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a complete or partial response to platinum-based chemotherapy, GSK said.
The primary endpoint of the phase 3 NOVA study was progression-free survival (PFS). Results demonstrated the clinically meaningful and statistically significant benefit of Zejula in both cohorts, as well as in subgroups of the non-germline BRCA mutations cohort, particularly patients with homologous recombination deficiency.
Secondary endpoints were safety and long-term exploratory endpoints, including overall survival. “GSK is in ongoing discussions about these and other emerging OS data with health authorities worldwide,” the pharmaceutical manufacturer said.
GSK continues to evaluate Zejula in trials across multiple tumors, including the FIRST phase 3 trial assessing niraparib in combination with dostarlimab, a PD-1-blocking antibody, as a potential treatment for first-line ovarian cancer maintenance and the phase 3 ZEAL trial assessing niraparib in combination with standard of care for the maintenance treatment of first-line advanced non-small cell lung cancer. GSK also is evaluating niraparib in HER2-negative BRCA-mutated or triple-negative breast cancer.
Merck and AstraZeneca voluntary withdrew an indication for another PARP-inhibitor, Lynparza (olaparib), after consulting with the FDA on Lynparza’s phase 3 trial results. “A recent subgroup analysis indicated a potential detrimental effect on overall survival for Lynparza compared to the chemotherapy control arm in the subgroup of patients who had received three or more lines of chemotherapy,” AstraZeneca said in a notice.
In July, Merck and AstraZeneca also announced that the phase 3 LYNK-003 trial investigating Lynparza with or without Genentech’s Avastin (bevacizumab) to treat patients with metastatic colorectal cancer was being stopped for futility.
Lynparza as a monotherapy and in combination with Avastin did not meet its objectives at a planned interim analysis. An independent data monitoring committee made the recommendation to discontinue both arms of the study. No new safety issues were seen, and the safety profile was similar to previous studies
Lynparza is approved for several indications, including advanced ovarian cancer, metastatic prostate cancer, metastatic pancreatic cancer, and early or metastatic breast cancer.