The European Commission has approved Zejula ( Niraparib ), an oral, once-daily PARP [ poly(ADP-ribose)polymerase ] inhibitor, as first-line monotherapy maintenance treatment for adult patients with advanced epithelial ( FIGO stages III and IV ) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response following Platinum-based chemotherapy.
This approval makes Zejula the only PARP inhibitor approved in the European Union for use as a monotherapy for patients with advanced ovarian cancer, regardless of their biomarker status.
Until now, only women with BRCA-mutant ( BRCAm ) ovarian cancer, representing just 20% of patients with advanced ovarian cancer, were eligible to be treated with a PARP inhibitor as monotherapy in the first-line maintenance setting.
In April 2020, the US Food and Drug Administration ( FDA ) approved a supplemental New Drug Application ( sNDA ) for Zejula in the United States for the same indication, which is supported by data from the pivotal phase 3 PRIMA study ( ENGOT-OV26 / GOG-3012 ) that demonstrated a clinically meaningful progression-free survival benefit of Zejula in the first-line maintenance setting.
The PRIMA study enrolled patients with newly diagnosed advanced ovarian cancer who responded to first-line treatment with Platinum-based chemotherapy, a population with high unmet needs and limited treatment options.
The primary endpoint in the PRIMA study was progression free survival analysed sequentially, first in the homologous recombination deficient ( HRd ) population, then in the overall population.
The PRIMA study has significantly improved progression-free survival for patients treated with Niraparib, regardless of biomarker status.
In the HRd population, Niraparib resulted in a 57% reduction in the risk of disease progression or death versus placebo ( hazard ratio, HR 0.43; 95% CI, 0.31 to 0.59; p less than 0.0001 ) and a 38% reduction in the risk of disease progression or death versus placebo in the overall population ( HR 0.62; 95% CI, 0.50 to 0.76; p less than 0.001 ).
In addition, there was a 60% reduction in risk of progression in those with BRCA mutation tumours ( HR 0.40; 95% CI, 0.27 to 0.62; p less than 0.001).
At initiation 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.
Niraparib’s safety profile, as demonstrated by the PRIMA results, was consistent with the previously observed clinical safety profile.
Lower rates of grade 3 and 4 haematologic treatment-emergent adverse events were observed with an individualised starting dose, compared to the overall population, including thrombocytopenia ( 21% compared to 39% ), anaemia ( 23% compared to 31% ) and neutropenia ( 15% compared to 21% ).
In Europe, ovarian cancer is the sixth deadliest cancer among women and more than 65,000 women are diagnosed each year.
Despite high response rates to Platinum-based chemotherapy in the first-line, approximately 85% of women with advanced ovarian cancer will develop recurrence. ( Xagena )
Source: GSK, 2020