Niraparib Grabs Regulatory Attention in China for Treatment of Advanced Ovarian Cancer

April 16, 2020

Niraparib was granted Priority Review in China as a maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, by the National Medical Products Administration.

Niraparib (Zejula) was granted Priority Review in China as a maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, by the National Medical Products Administration, according to a press release from Zai Lab Limited.1

The supplemental New Drug Application for niraparib was accepted in February 2020, based on results from the phase III PRIMA/ENGOT-OV26/GOG-3012 study. The latest efficacy data were released in an abstract for presentation at the 2020 Society for Gynecologic Oncology (SGO) Annual Meeting, which showed that niraparib statistically and significantly improved progression-free survival (PFS) in patients with advanced ovarian cancer and the agent showed no new safety signals.2

In the study, 733 patients were randomized 2:1 to receive niraparib (n = 487) or placebo (n = 246). A subgroup of patients were homologous recombination deficient (HRD)—positive and was divided between the niraparib arm (n = 247) and the placebo arm (n = 126). Another subgroup was homologous recombination proficient and 169 of these patients were in the niraparib arm and 80 were in the placebo arm. In terms of baseline characteristics, 35% of patients had stage IV disease, 67% had received chemotherapy in the neoadjuvant setting, and 31% had a partial response to first-line chemotherapy.

Treatment with niraparib led to a median PFS of 21.9 months with niraparib compared with 10.4 months with placebo (hazard ratio [HR], 0.43; 95% CI, 0.31-0.59;P<.001), among patients with HRD-positivity. In the overall study population, the median PFS was 13.8 months with niraparib and 8.2 months with placebo (HR, 0.62; 95% CI, 0.50-0.76; P<.001).3

The 24-month interim analysis revealed data for the secondary end point, overall survival (OS). The OS rate observed with niraparib was 84% versus 77% in the placebo group (HR for death, 0.70; 95% CI, 0.44-1.11), in the overall population. For patients with HRD-positivity, the OS rate was 91% in the niraparib group and 85% in the placebo group (HR, 0.61; 95% CI, 0.27-1.39).

The exploratory analysis looked for differences in PFS and OS between patients with and withoutBRCAmutations.

For patients with HRD-positivity, median duration of PFS was 22.1 months in the niraparib group versus 10.9 months in the placebo group (HR, 0.40; 95% CI, 0.27-0.62) among patients withBRCA-mutant disease. For those withoutBRCAmutations, the PFS was 19.6 months in the niraparib group versus 8.2 months in the placebo group (HR, 0.50; 95% CI, 0.31-0.83). In the subgroup of patients with HRD-negativity, the median PFS was 8.1 months in the niraparib group compared with 5.4 months in the placebo group (HR, 0.68; 95% CI, 0.49-0.94). Overall, the BRCA-mutated group versus the patient withoutBRCAmutations had 24-month OS rates of 81% versus 59%, respectively (HR, 0.51; 95% CI, 0.27-0.97).

In terms of safety, anemia (31%), thrombocytopenia (29%), and neutropenia (13%) were the most common grade 3 or higher adverse events observed.2Over 70% of patients in the niraparib group required dose reductions. Treatment discontinuation occurred in 12.0% of patients in the niraparib group and 2.5% in the placebo group. The leading reason for treatment discontinuation was myelosuppressive adverse events.

In the United States,niraparib is approved for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancertreated with ≥3 prior chemotherapy regimens and whose cancer is associated with HRD-positivity.

References

  1. Zai Lab announces china&rsquo;s nmpa grants priority review to the snda for zejula (niraparib) for first-line ovarian cancer maintenance treatment [news release]. Shanghai, China: Zai Lab Limited: April 16, 2020.https://bit.ly/3aiojBo. Accessed April 16, 2020.
  2. Monk BJ and Marton AG. Efficacy of niraparib therapy in patients with newly diagnosed advanced ovarian cancer by BRCA&nbsp;and homologous recombination status: PRIMA/ENGOT-OV26/GOG-3012 study. Data made available as part of the virtual platform for the SGO 2020 Annual Meeting. Abstract 31.
  3. Marton AG, Pothuri B, Vergote I, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.N Engl J Med.2019; 381:2391-2402. DOI: 10.1056/NEJMoa1910962