GSK takes fight to AZ/Merck & Co with first-line ovarian cancer approval

The FDA has approved GlaxoSmithKline’s Zejula as first-line maintenance treatment for women with platinum-responsive ovarian cancer, competing against AstraZeneca and Merck & Co’s class rival without the need for a biomarker test. 

Zejula (niraparib) is a once daily oral PARP inhibitor and following this new approval is the only drug in its class that can be used as first-line maintenance monotherapy without needing a test for the BRCA mutation. 

The approval without the BRCA test also allows for the drug to be used in a much wider patient group. 

AZ and Merck & Co’s Lynparza (olaparib) is limited to use in around 20% of patients eligible for maintenance therapy because it needs the presence of BRCA mutations to be effective. 

GSK’s indication covers women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy regardless of biomarker status. 

The new indication is supported by data from the phase 3 PRIMA study, which enrolled patients with newly diagnosed advanced ovarian cancer following a complete or partial response to platinum-based chemotherapy regardless of biomarker status. 

The PRIMA study enrolled women who had higher risk of disease progression, a population with high unmet needs and limited treatment options. 

The primary endpoint in PRIMA was progression-free survival (PFS) analysed sequentially first in patients with BRCA-like mutations, then in the overall population.

Results showed Zejula significantly improved PFS regardless of biomarker status – in patients with homologous recombination deficiency (HRd) mutations, Zejula resulted in a 57% reduction in risk of disease progression versus placebo. 

In the overall population there was a 38% reduction in the risk of disease progression or death compared with placebo. 

There were new surprises in terms of safety with the most common grade 3 or higher adverse events with Zejula including low platelet count (39%), anaemia (31%) and neutropenia (21%). 

At the start of the PRIMA study, patients received a fixed starting dose of 300 mg of Zejula once-daily. The study was later amended to incorporate an individualised starting dose of either 200 mg or 300 mg of Zejula once-daily based on the patient’s baseline weight and/or platelet count. 

The individualised starting dose cut the rates of grade 3 or 4 haematologic side effects, the study showed.