Maintenance niraparib improved progression-free survival in Chinese patients with recurrent ovarian cancer who were in a complete or partial response to platinum-based chemotherapy, meeting the primary end point of the phase 3 NORA study.
Maintenance niraparib (Zejula) improved progression-free survival (PFS) versus placebo in Chinese patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were in a complete or partial response to platinum-based chemotherapy, meeting the primary end point of the phase 3 NORA study.1
“The data of the NORA study will have a significant impact on the clinical practice in the treatment of ovarian cancer in China and beyond, as the individualized starting dose regimen has demonstrated clear clinical benefit with improved safety profile,” said Xiaohua Wu, MD, professor and chair of Gynecologic Oncology Department of Fudan University Shanghai Cancer Centre, stated in a press release. “In addition, the NORA study is the first fully powered, randomized, controlled phase 3 trial ever done in ovarian cancer in China.”
The double-blind phase 3 NORA study included 265 Chinese patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who were in a complete or partial response to platinum-based chemotherapy. Patients were randomized in a 2:1 ratio to receive maintenance niraparib or placebo. Patients received a starting dose of 200 mg of niraparib, except for patients with a bodyweight at baseline of >77kg and a platelet count >150K/μL, who began at a dose of 300 mg.
Zai Lab reported in a press release that the topline NORA findings were consistent with the data previously reported in the global phase 3 NOVA study. In March 2017, based on the NOVA study, 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. The data the FDA reviewed at the time showed that niraparib reduced the risk of progression or death by 74% compared with placebo for patients with germline BRCA-positive platinum-sensitive, recurrent ovarian cancer.2,3
The median PFS with maintenance niraparib was 21 months compared with 5.5 months for placebo in patients with germline BRCA mutations (HR, 0.26; 95% CI, 0.17-0.41; P <.0001). These findings remained consistent across subgroups of patients, including those without BRCA mutations.
The phase 3 NOVA study randomized patients in a 2:1 ratio across 2 independent cohorts. In the first cohort, 201 patients with germline BRCA mutations received niraparib at 300 mg daily (n = 138) or placebo (n = 65). In the second cohort, 345 patients with non-germline BRCA-mutant tumors received the PARP Inhibitor (n = 231) or placebo (n = 114). Patients in this group were tested for homologous recombination deficiency (HRD), and could be either positive (n = 162) or negative (n = 134). Of those who tested positive, 47 had somatic BRCA mutations and 115 were wild-type.
Patient demographics were well balanced between the arms for each cohort. In the germline BRCA group, the median age was 57 years and 65.9% had an ECOG performance status (PS) of 0. In the placebo group, the median age was 58 years and 73.8% of patients had an ECOG PS of 0. Overall, 48.6% and 53.8% of patients had received ≥3 prior therapies, in the niraparib and placebo arms, respectively.
Across both cohorts, the majority of patients had stage III cancer (68.8% to 74.1%). Approximately half of patients had achieved a complete response to prior platinum-based therapy and a quarter had received prior bevacizumab. In the non-BRCA-mutant arm, 33.8% and 32.8% of patients had received ≥3 prior therapies.
In the germline BRCA mutation group, the chemotherapy-free interval was 22.8 months with niraparib compared with 9.4 months for placebo (HR, 0.26; 95% CI, 0.17-0.41; P <.001). The median time to subsequent therapy was 21 months with niraparib versus 8.4 months with placebo (HR, 0.31; 95% CI, 0.21-0.48).
In patients with HRD-positive, BRCA wild-type tumors, median PFS was 9.3 versus 3.7 months for niraparib and placebo, respectively (HR, 0.38; 95% CI, 0.23-0.63; P <.001). In those with HRD-positive, somatic BRCA-mutated tumors, the median PFS was 20.9 months with niraparib versus 11.0 months for placebo (HR, 0.27; 95% CI, 0.08-0.90; P = .02). In patients with HRD-negative, non-germline BRCA-mutated tumors, median PFS was 6.9 versus 3.8 months for niraparib and placebo, respectively (HR, 0.58; 95% CI, 0.36-0.92; P = .02).
In those with non-germline BRCA mutations regardless of HRD status, the median chemotherapy-free interval was 12.7 versus 8.6 months for niraparib and placebo, respectively (HR, 0.50; 95% CI, 0.37-0.67; P <.001). The median time to subsequent therapy was 11.8 versus 7.2 months (HR, 0.55; 95% CI, 0.41-0.72; P <.001) and the median PFS2 was 18.6 and 15.6 months for the niraparib and placebo arms, respectively (HR, 0.69; 95% CI, 0.49-0.96; P = .03).
Across cohorts, 14.7% of 367 niraparib-treated patients discontinued therapy due to an adverse event (AE) compared with 2.2% of the 179 patients in the placebo arm. There were no treatment-related deaths in the study. In the follow-up period, 1 patient in the niraparib arm and 2 in the placebo group died of myelodysplastic syndrome or acute myeloid leukemia. One of these deaths in each arm was deemed to be treatment related.
The most common all-grade AEs for niraparib versus placebo, respectively, were nausea (73.6% vs 35.2%, respectively), thrombocytopenia (61.3% vs 5.6%), fatigue (59.4% vs 41.3%), anemia (50.1% vs 6.7%), constipation (39.8% vs 20.1%), vomiting (34.3% vs 16.2%), and neutropenia (30.2% vs 6.1%).
The most common grade 3/4 AEs in the niraparib arm were hematologic, and included thrombocytopenia (33.8%), anemia (25.3%), and neutropenia (19.6%). The most common non-hematologic AEs were hypertension (8.2%), fatigue (8.2%), and nausea (3%). A majority of hematologic AEs were experienced in the first 3 cycles.
The PFS benefit was observed regardless of patient biomarker status. No new safety signals emerged with niraparib compared with previous studies of the PARP inhibitor, according to Zai Lab Limited, which has the rights to market niraparib in Mainland China, Hong Kong, and Macau.