The China National Medical Products Administration has approved niraparib for use as a first-line maintenance treatment in adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who achieve a complete or partial response to first-line platinum-based chemotherapy.
The China National Medical Products Administration (NMPA) has approved niraparib (Zejula) for use as a first-line maintenance treatment in adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who achieve a complete or partial response to first-line platinum-based chemotherapy, according to an announcement from Zai Lab Limited.1
“We believe [niraparib] is a potential best-in-class PARP inhibitor. It is the first and only PARP inhibitor approved anywhere globally, including in China as monotherapy for all-comer patients in the first-line and recurrent maintenance treatment settings,” Samantha Du, PhD, founder, chairwoman, and chief executive officer of Zai Lab, stated in a press release. “The NMPA’s rapid approval of our supplemental new drug application (sNDA) for [niraparib] underscores the unmet medical need it serves and further establishes Zai Lab to make a meaningful impact on the way ovarian cancer is treated in China.”
The regulatory decision is based on data from the phase 3 PRIMA trial (ENGOT-OV26/GOG-3012; NCT02655016), which showed that frontline maintenance therapy with the small molecule PARP inhibitor prolonged the median progression-free survival (PFS) of patients with newly diagnosed, advanced ovarian cancer who responded to platinum-based chemotherapy by 5.6 months versus placebo.2,3
The median PFS in the overall study population was 13.8 months with niraparib versus 8.2 months with placebo; this translated to a 38% reduction in the risk of progression or death (HR, 0.62; 95% CI, 0.50-0.76; P <.001). In participants with homologous recombination deficiency (HRD) positivity, the median PFS was 21.9 months in the niraparib arm versus 10.4 months in the placebo arm (HR, 0.43; 95% CI, 0.50-0.76; P <.001).
In the double-blind, randomized, placebo-controlled, phase 3 trial, a total of 733 participants underwent randomization in a 2:1 fashion to either niraparib (n = 487) or placebo (n = 246). Patients were randomized within 12 weeks of completing the 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 adjusted to include a lower dose of 200 mg for patients who weighed less than 77 kg as well as for those with platelet counts that fell below 150L/μL. Additionally, the median relative dose intensity in the trial was 63%.
Approximately 70% of patients had an ECOG performance status of 1, two-thirds had a FIGO stage of III, and one-third had stage IV disease. The primary tumor locations included ovarian, fallopian tube, and peritoneum. Approximately 95% of patients were determined to have serous histology and two-thirds of participants had received neoadjuvant chemotherapy. Notably, none of the patients had received bevacizumab (Avastin) because the trial was designed before the agent was approved for use in the first-line setting.
The median overall survival (OS) with the agent 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 overall 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 subgroup of patients with HRD positivity, the 24-month OS rates were 91% versus 85% with niraparib and placebo, respectively (HR, 0.61; 95% CI, 0.27-1.39).
Among those in the HRD subgroup, investigators also examined PFS in those whose tumors harbored BRCA mutations. For those with BRCA-mutated disease, the median PFS was 22.1 months versus 10.9 months with niraparib and placebo, respectively (HR, 0.40; 95% CI, 0.27-0.62). Those in this subgroup who did not harbor the mutation experienced a median PFS of 19.6 months with niraparib versus 8.2 months with placebo (HR, 0.50; 95% CI, 0.31-0.83).
Niraparib was also found to improve the median PFS in patients with HRD negativity compared with placebo, at 8.1 months versus 5.4 months, respectively (HR, 0.68; 95% CI, 0.49-0.94). The 24-month OS rate in this subgroup was 81% with niraparib versus 59% with placebo (HR, 0.51; 95% CI, 0.27-0.97).
With regard to safety, more any-grade treatment-related adverse effects (TRAEs) were reported with the PARP inhibitor compared with placebo, at 96.3% versus 68.9%, respectively. TRAEs that were grade 3 or higher were reported in 65.3% of patients who received niraparib versus 6.6% of patients who were given placebo. The most commonly experienced grade 3 or higher toxicities included anemia (31.0% with niraparib vs 1.6% with placebo), thrombocytopenia (28.7% vs 0.4%, respectively), platelet count decrease (13.0% vs 0%), and neutropenia (12.8% vs 1.2%).
Moreover, 70.9% of participants who received niraparib required a dose reduction and 12% experienced toxicities that resulted in treatment discontinuation. The main AEs that resulted in discontinuation were myelosuppressive in nature, such as thrombocytopenia (4.3%).
Niraparib monotherapy is approved as a maintenance treatment in the United States for patients with recurrent ovarian cancer. The agent is also approved for use in patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who received treatment with 3 or more chemotherapy regimens and whose cancer is HRD positive.
In April 2020, the FDA approved niraparib for use as 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-based chemotherapy, irrespective of biomarker status. The decision was based on data from PRIMA.
“The approval of [niraparib] for the first-line maintenance treatment setting represents an opportunity to fundamentally change how women with ovarian cancer will be treated in China and a new standard of care for these patients,” Lingying Wu, MD, director of the Department of Gynecologic Oncology of the Cancer Hospital of China Academy of Medical Sciences, added in the release. “In addition to its compelling efficacy data as monotherapy for all-comer patients, [niraparib] also has the convenience of once-daily dosing, excellent safety profile, and attractive pharmacokinetic properties, including its ability to cross the blood-brain barrier.”