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Niraparib as a maintenance treatment demonstrated a statistically significant improvement in progression-free survival compared with placebo in patients with ovarian cancer following first-line platinum-based chemotherapy, regardless of biomarker status, meeting the primary endpoint of the phase III PRIMA (ENGOT-OV26/GOG-3012) trial.
Hal Barron, MD
Niraparib (Zejula) as a maintenance treatment demonstrated a statistically significant improvement in progression-free survival (PFS) compared with placebo in patients with ovarian cancer following first-line platinum-based chemotherapy, regardless of biomarker status, meeting the primary endpoint of the phase III PRIMA (ENGOT-OV26/GOG-3012) trial.1
The safety and tolerability profile of the PARP inhibitor was also found to be consistent with prior clinical studies, stated GlaxoSmithKline, the developer of niraparib, in a press release. Full findings of the study will be presented at an upcoming medical meeting.
“Almost 300,000 women around the world are diagnosed with ovarian cancer every year, yet only about 15% of patients are currently eligible to receive PARP inhibitors as their initial therapy,” Hal Barron, MD, chief scientific officer and president, R&D, GlaxoSmithKline, stated in the press release. “These exciting data demonstrate that Zejula has the potential to significantly benefit even more women with this devastating cancer.”
In the phase III, randomized, double-blind, placebo-controlled PRIMA trial (NCT02655016), investigators compared maintenance niraparib with placebo in approximately 620 patients with stage III/IV ovarian cancer. Patients who had responded to first-line platinum-based chemotherapy were randomized 2:1 to receive either niraparib at a starting dose of 200 mg daily in those with baseline weight <77 kg or platelet count <150K/μL and 300 mg in all other patients, or placebo.
To be eligible for enrollment, patients must have had histologically confirmed, advanced, stage III/IV, high-grade predominantly serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have completed frontline-platinum based chemotherapy; must have had a complete or partial response to chemotherapy; agreed to undergo central tumor HRD testing; and be randomized to study treatment within 12 weeks of the first day of the last cycle of chemotherapy.
Those with mucinous or clear cell subtypes of epithelial ovarian, carcinosarcoma, or undifferentiated ovarian cancer; had >2 debulking surgeries, were slated to receive bevacizumab (Avastin) treatment, were pregnant, had prior treatment with a PARP inhibitor, and were diagnosed and/or treated for any other invasive cancer <5 years prior to study enrollment were excluded from the trial.
The primary endpoint was PFS; secondary endpoints were overall survival, safety and tolerability, and patient-reported outcomes. Other outcome measures include area under the curve (AUC)0-last, AUC, peak plasma concentration, and homologous recombination deficiency (HRD) diagnostic test.
The FDA approved niraparib for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy, in March 2017.
Most recently, in June 2019, the FDA granted a priority review designation to a supplemental biologics license application for niraparib for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥3 or more prior chemotherapy regimens, and who have either a BRCA mutation or have HRD and progressed >6 months after their last platinum-based chemotherapy.
The designation is based on data from the multicenter, open-label, single-arm, QUADRA study, in which researchers evaluated the safety and efficacy of niraparib in 463 adult patients with metastatic, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who previously received ≥3 lines of chemotherapy.
In the study, patients received oral niraparib at 300 mg daily continuously, beginning on day 1 in 28-day cycles until disease progression. The primary endpoint was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with HRD-positive tumors—which include both patients with and without BRCA mutations—who were sensitive to their most recent platinum-based therapy who had received 3 or 4 prior anticancer therapies. Also, efficacy analyses were conducted in all dosed patients with measurable disease at baseline.
Results showed that the overall response rate (ORR) was 28% (95% CI, 15.6-42.6; P = .00053) in the primary efficacy population of patients who had HRD and who received ≥3 prior lines of therapy.2
Under the Prescription Drug User Fee Act, the FDA must make a decision on the application by October 24, 2019.