GlaxoSmithKline's Zejula cleared in US for late-line treatment of recurrent ovarian cancer

GlaxoSmithKline announced Thursday that the FDA approved its filing to expand the label for Zejula (niraparib) to include patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with at least three prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status. "This represents the first time a PARP inhibitor has been approved for use in patients beyond those with a BRCA-positive mutation as monotherapy in the late-line treatment setting," the company noted. 

The decision was based on Phase II results from the single-arm QUADRA study, which assessed Zejula monotherapy in a broad population of 461 patients, including women with BRCA-positive, platinum-sensitive, -resistant and -refractory disease, as well as women with HRD-positive, platinum-sensitive disease. The primary endpoint was the proportion of patients achieving an investigator-assessed confirmed overall response. Other objectives looked at Zejula efficacy in the broad late-line ovarian cancer population overall, and in subgroups defined by clinical and molecular biomarkers, such as platinum-sensitivity and BRCA-mutation and HRD status. 

GlaxoSmithKline said clinically meaningful and durable benefit was demonstrated in the FDA-indicated patient population with an objective response rate (ORR) of 24%, and a median duration of response of 8.3 months. 

Testing done in various subpopulations showed that Zejula was also effective in patients with deleterious somatic or germline BRCA mutations (tBRCA) and a genomic instability score (GIS) of at least 42. Specifically, ORRs in tBRCA patients was 39% for those with platinum-sensitive disease and 29% for platinum-resistant disease, while tBRCA patients with platinum-refractory disease achieved an ORR of 19%. In addition, among non-BRCA-mutated patients who had GIS-positive, platinum-sensitive disease, the ORR was of 20%. 

GlaxoSmithKline said Zejula's safety profile was consistent with that seen in the Phase III NOVA trial in the recurrent maintenance population. The most common adverse reactions of grade 3 or higher reported in the QUADRA study included thrombocytopaenia, anaemia, neutropaenia and nausea. 

GlaxoSmithKline gained Zejula, which had sales of £57 million pounds ($73 million) in the second quarter, as part of its $5.1-billion takeover of Tesaro earlier this year. The drug is currently approved in the US and Europe as a treatment for adults with recurrent ovarian cancer, regardless of BRCA mutation or biomarker status. 

Other PARP inhibitors cleared in the US include AstraZeneca's Lynparza (olaparib), Pfizer's Talzenna (talazoparib) and Clovis Oncology's Rubraca (rucaparib), while AbbVie is developing the experimental PARP inhibitor veliparib. 

For related analysis, see ViewPoints: GlaxoSmithKline's push back into oncology gets a lift in the right direction

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