FDA has approved a supplemental New Drug Application for Zejula (niraparib) an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor, as a monotherapy maintenance treatment for 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.
Until now, only 20% of women with ovarian cancer, those with a BRCA mutation, were eligible to be treated with a PARP inhibitor as monotherapy in the first-line maintenance setting.
GlaxoSmithKline sponsors Zejulia.
Efficacy was investigated in PRIMA (NCT02655016), a double-blind, placebo-controlled trial that randomized 733 patients to niraparib or matched placebo. Patients were in a complete or partial response to first-line platinum-based chemotherapy.
“PRIMA was designed for patients with ovarian cancer who have a high unmet need. The positive data observed regardless of biomarker status in this study is extremely encouraging and suggests benefit beyond the BRCAm population,” Bradley Monk, PRIMA investigator, US Oncology, University of Arizona College of Medicine, Phoenix Creighton University School of Medicine at St. Joseph’s Hospital Phoenix, said in a statement. “This approval is an important step forward in the treatment of ovarian cancer. In my opinion, maintenance treatment with niraparib should be considered an option for appropriate patients who responded to first-line platinum-based chemotherapy versus active surveillance.”
The main efficacy outcome measure, progression-free survival, was first tested in the homologous recombination deficient population, then in the overall population and was determined by blinded independent central review per RECIST 1.1. Tumor samples were tested for homologous recombination deficiency status; homologous recombination deficient was defined by either presence of tumor breast cancer susceptibility gene mutation or genomic instability score ≥42. An FDA-approved companion diagnostic is not required to initiate treatment with ZEJULA for this indication.
The trial demonstrated a statistically significant improvement in PFS for patients randomized to niraparib compared with placebo in the homologous recombination deficient and overall population. Median PFS in the homologous recombination deficient population was 21.9 months (19.3, NE) for patients receiving niraparib compared with 10.4 months (8.1, 12.1) for those receiving placebo (HR 0.43; 95% CI: 0.31, 0.59; p<0.0001). Median PFS in the overall population was 13.8 months (11.5, 14.9) for patients receiving niraparib compared with 8.2 months (7.3, 8.5) for those receiving placebo (HR 0.62; 95% CI: 0.50, 0.76; p<0.0001).
“It’s so important for patients with ovarian cancer to have treatment options, and this approval is positive news for our community,” Audra Moran, president and CEO, Ovarian Cancer Research Alliance, said in a statement. “PARP inhibitors represent a major advancement in the fight against ovarian cancer, and having a new first-line maintenance option for platinum-responsive advanced ovarian cancer patients—regardless of BRCA mutation status—is especially exciting. We are determined to keep funding research and partnering with scientists who are on the frontline of finding new treatments like this one to help those impacted by this disease.”
PRIMA study results were previously presented at the 2019 European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine.
