FDA expands Zejula approval for gynecologic cancers
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The FDA expanded the approval of niraparib for gynecologic cancers.
The new indication applies to use of niraparib (Zejula, Tesaro/GlaxoSmithKline) — a poly(ADP-ribose) polymerase (PARP) inhibitor — to treat women with advanced ovarian, fallopian tube or primary peritoneal cancers who underwent at least three prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency-positive status.
“This new indication reinforces our commitment to providing treatment options for more women impacted by ovarian cancer, especially those with high unmet needs,” Axel Hoos, MD, PhD, senior vice president of oncology research and development at GlaxoSmithKline, said in a company-issued press release. “We look forward to continuing our clinical development program of Zejula and understanding its full potential as a treatment for people living with ovarian cancer.”
The FDA also approved the Myriad myChoice CDx (Myriad Genetics) companion diagnostic to measure tumor homologous recombination deficiency status to select patients for niraparib.
Homologous recombination deficiency status is determined either by presence of a deleterious or suspected deleterious BRCA mutation, or by genomic instability among patients whose disease progressed more than 6 months after response to their most recent platinum-based chemotherapy.
The FDA previously approved niraparib for maintenance treatment of women with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
The agency based the new indication on results of the single-arm QUADRA trial, which included 98 women with advanced ovarian cancer who had homologous recombination deficiency-positive tumors, had undergone at least three lines of prior chemotherapy, and had no prior exposure to PARP inhibitors.
Investigators used the Myriad myChoice CDx companion diagnostic to identify BRCA mutations (n = 63) and/or a genomic instability score of 42 or higher (n = 35). Women without BRCA mutations had progressed at least 6 months after their most recent dose of platinum-based therapy.
All women in the study received niraparib dosed at 300 mg once daily. Treatment continued until disease progression or unacceptable toxicity.
Objective response rate and duration of response served as primary outcome measures.
Researchers reported an ORR of 24% (95% CI, 16-34) — with all responses being partial responses — and an estimated median duration of response of 8.3 months (95% CI, 6.5-not estimable).
Among women with BRCA-mutated ovarian cancer, results showed ORRs of 39% (95% CI, 17-64) for those with platinum-sensitive disease, 29% (95% CI, 11-52) for those with platinum-resistant disease and 19% (95% CI, 4-46) for those with platinum-refractory disease.
Researchers reported an ORR of 20% (95% CI, 8-37) among women who did not have BRCA mutations but had genomic instability score-positive, platinum-sensitive disease.
“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,” Kathleen Moore, MD, associate director of clinical research at Stephenson Cancer Center at University of Oklahoma College of Medicine, said in a press release. “It’s meaningful to see that Zejula has been approved as a late-line treatment for women including those with and without BRCA mutations.”
Nearly three-quarters (73%) of patients required dose reductions or interruption due to adverse reactions, the most common of which were thrombocytopenia (40%), anemia (21%), neutropenia (11%), nausea (13%), vomiting (11%), fatigue (9%) and abdominal pain (5%).