The Food and Drug Administration (FDA) has expanded the indication for Zejula (niraparib; GlaxoSmithKline) for the treatment of advanced ovarian, fallopian tube, or primary peritoneal cancer patients, who have been treated with ≥3 prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:
- A deleterious or suspected deleterious BRCA mutation, or
- Genomic instability and who have progressed more than 6 months after response to the last platinum-based chemotherapy.
The approval is supported by data from the phase 2, multicenter, open-label, single-arm QUADRA study that evaluated the efficacy and safety of niraparib in 98 patients with advanced ovarian cancer with HRD-positive tumors who have received ≥3 prior chemotherapy regimens. HRD positive status was determined using the Myriad myChoice CDx as either tBRCAm (n=63) and/or a genomic instability score (GIS) ≥42 (n=35). All patients received niraparib 300mg once daily as monotherapy. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR), assessed by RECIST v1.1.
Results demonstrated niraparib treatment was associated with a clinically meaningful and durable benefit in the FDA-indicated patient population with an ORR of 24% (95% CI: 16, 34) and a median DOR of 8.3 months (95% CI: 6.5, not estimable).
Additionally, objective response with niraparib was assessed in various subgroups:
- tBRCA+ platinum-sensitive: ORR of 39% (95% CI: 17, 64)
- tBRCA+ platinum-resistant: ORR of 29% (95% CI: 11, 52)
- tBRCA+ platinum-refractory: ORR of 19% (95% CI: 4, 46)
- Platinum-sensitive GIS-positive (without BRCAmut): ORR of 20% (95% CI: 8, 37)
The safety profile of niraparib was consistent with that observed in the phase 3 NOVA trial. The most common grade ≥3 adverse reactions (≥10%) were thrombocytopenia (28%), anemia (27%), and neutropenia (13%); serious adverse reactions (>3%) included small intestinal obstruction (7%), vomiting (6%), nausea (5%), and abdominal pain (4%).
Commenting on the approval, Dr Kathleen Moore, lead Investigator of the QUADRA study; Director, Oklahoma TSET Phase 1 Program; Associate Professor, Section of Gynecologic Oncology, Stephenson Cancer Center, University of Oklahoma, said, “Ovarian cancer has a high rate of recurrence, so there is a real need for therapies for women whose cancer has progressed through multiple lines of treatment and who have few or no options left. It’s meaningful to see that Zejula has been approved as a late-line treatment for women including those with and without BRCA mutations.”
Zejula, a poly(ADP-ribose) polymerase (PARP) inhibitor, is also approved for maintenance treatment in adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. It is available as 100mg strength capsules in 30- and 90-count bottles.
For more information visit zejula.com.