Niraparib Granted Positive EU Opinion for Frontline Maintenance in Advanced Ovarian Cancer


The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for niraparib for frontline maintenance treatment in patients with advanced ovarian cancer who are responsive to platinum-based chemotherapy.

Axel Hoos, MD, PhD

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for niraparib (Zejula) for frontline maintenance treatment in patients with advanced ovarian cancer who are responsive to platinum-based chemotherapy, according to an announcement from GlaxoSmithKline (GSK).1

The Type II variation application was based on findings from the pivotal phase 3 PRIMA study (ENGOT-OV26/GOG-3012; NCT02655016), which showed that the use of niraparib in the first-line maintenance setting resulted in a clinically meaningful progression-free survival (PFS) benefit in newly diagnosed patients with advanced ovarian cancer who had responded to frontline platinum-based chemotherapy.

“Only 20% of women with ovarian cancer are currently eligible to be treated with a PARP inhibitor in the first-line maintenance setting,” Axel Hoos, MD, PhD, senior vice president and head of Oncology R&D at GSK, stated in a press release. “Today’s positive opinion from the CHMP will give all women in response to platinum-based chemotherapy the option to receive [niraparib] in the maintenance setting, reinforcing our belief in the important role this innovative medicine may play in helping these patients and the physicians working to treat them.”

Results from the phase 3 trial showed that maintenance niraparib resulted in a median PFS of 13.8 months versus 8.2 months with placebo; this translated to a 38% reduction in the risk of progression or death with the PARP inhibitor (HR, 0.62; 95% CI, 0.50-0.76; P <.0001).2 In patients who had homologous recombination deficiency (HRD) positivity, the median PFS was 21.9 months with niraparib versus 10.4 months with placebo (HR, 0.43; 95% CI, 0.31-0.59; P <.0001).

In the phase 3 trial, a total of 733 patients were randomized 2:1 to receive niraparib (n = 487) or placebo (n = 246). Participants underwent randomization within 12 weeks of completing their last cycle of chemotherapy. At the start of the study, the PARP inhibitor was administered at a fixed dose of 300 mg; this was then reduced to a dose of 200 mg for patients who weighed less than 77 kg and those with platelet counts below 150K/μL. The median relative dose intensity in PRIMA was 63%.

Patient characteristics were comparable across the arms. Seventy percent of participants had an ECOG performance status of 1 and two-thirds had a FIGO stage of III; one-third of patients had stage IV disease. The primary tumor locations of participants included ovary, fallopian tube, and peritoneum. Most of the patients, or approximately 95%, had serous histology.

Moreover, 70% of participants had experienced a complete response to previous chemotherapy, two-thirds of patients had received neoadjuvant chemotherapy, and none received bevacizumab (Avastin).

The median overall survival (OS) with niraparib had not yet been reached at the time of the interim analysis; data maturity was just 10.8%. The 24-month OS rate in the full study population was 84% in the investigational arm versus 77% in the control arm (HR, 0.70; 95% CI, 0.44-1.11). In the HRD-positive subgroup, the 24-month OS rates with the PARP inhibitor and placebo were 91% versus 85%, respectively (HR, 0.61; 95% CI, 0.27-1.39).

Of those in the HRD-positive cohort, those whose tumor harbored a BRCA mutation experienced a median PFS of 22.1 months with the PARP inhibitor versus 10.9 months with placebo (HR, 0.40; 95% CI, 0.27-0.62). Among those with HRD positivity who did not harbor this mutation, the median PFS with niraparib and placebo was 19.6 months versus 8.2 months, respectively (HR, 0.50; 95% CI, 0.31-0.83).

Niraparib showed superior PFS benefit over placebo across all subgroups analyzed, including in patients those tumors were HRD negative. In this group, the median PFS with the PARP inhibitor was 8.1 months versus 5.4 months with placebo (HR, 0.68; 95% CI, 0.49-0.94). Interim OS data for this subgroup showed a 24-month OS rate of 81% with niraparib versus 59% with placebo (HR, 0.51; 95% CI, 0.27-0.97).

Regarding safety, those in the niraparib arm experienced more any-grade treatment-related toxicities than those in the placebo arm, at 96.3% versus 68.9%, respectively. Moreover, 65.3% of patients in the investigational arm reported treatment-related adverse effects (TRAEs) that were grade 3 or higher in severity versus 6.6% of those in the control arm.

The most commonly reported grade 3 or higher effects included anemia (31.0%, niraparib vs 1.6%, placebo), thrombocytopenia (28.7% vs 0.4%, respectively), decrease in platelet count (13.0% vs 0%), and neutropenia (12.8% vs 1.2%).

Additionally, 70.9% of patients in the niraparib arm required a dose reduction, while 12% discontinued treatment because of toxicities. The key toxicities that led to discontinuation of treatment were myelosuppressive in nature, with 4.3% of patients discontinuing due to thrombocytopenia.

Patient-reported outcomes data from the trial will be presented during the 2020 ESMO Virtual Congress.

In April 2020, niraparib received approval from the FDA for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-containing chemotherapy, irrespective of biomarker status. On September 10, 2020, the China Medicinal Products Administration approved niraparib for the same indication.

Previously, the PARP inhibitor was approved for use as a maintenance treatment in the recurrent ovarian setting. Niraparib is also indicated for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who received 3 or more prior chemotherapy regimens, and whose cancer does not have HRD positivity.


  1. GSK receives CHMP positive opinion for recommending approval of Zejula (niraparib) as first-line monotherapy maintenance treatment for women with platinum-responsive advanced ovarian cancer. News release. GSK. September 18, 2020. Accessed September 18, 2020.
  2. FDA approves niraparib for first-line maintenance of advanced ovarian cancer. News release. FDA. April 29, 2020. Accessed September 18, 2020.
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