Maintenance with niraparib significantly prolongs progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer, according to a phase 3 trial published in Annals of Oncology.
The results also suggest that an individualized starting dose (ISD) of niraparib, based on baseline body weight and platelet count, is safe and effective.
The phase 3 NORA trial (ClinicalTrials.gov Identifier: NCT03705156) was conducted at 30 study centers in China. It included 265 patients with recurrent ovarian cancer who had responded to platinum-containing chemotherapy.
The patients were randomly assigned to receive niraparib (177 patients) or placebo (88 patients) maintenance. An ISD of niraparib or placebo was given to 249 patients, 235 patients received a 200 mg dose, and 14 patients received a 300 mg dose.
In the intention-to-treat population, the median PFS was significantly longer with niraparib than with placebo — 18.3 months and 5.4 months, respectively (hazard ratio [HR], 0.32; 95% CI, 0.23-0.45; P <.0001).
The PFS was also longer with niraparib among patients who received an ISD. In this group, the median PFS was 18.3 months with niraparib and 5.4 months with placebo (HR, 0.30; 95% CI, 0.21-0.43).
The PFS benefit with niraparib was independent of BRCA mutation status. Among patients with germline BRCA mutations, the median PFS was not reached in the niraparib arm and was 5.5 months in the placebo arm (HR, 0.22; 95% CI, 0.12-0.39).
Among patients without germline BRCA mutations, the median PFS was 11.1 months in the niraparib arm and 3.9 months in the placebo arm (HR, 0.40; 95% CI, 0.26-0.61).
There was a significantly longer median chemotherapy-free interval in patients receiving niraparib than in those receiving placebo — 18.5 months and 9.7 months, respectively (HR, 0.34; 95% CI, 0.24-0.48; P <.0001).
The median time to first subsequent treatment was 16.7 months in the niraparib arm and 7.7 months in the placebo arm (HR, 0.35; 95% CI, 0.25-0.49; P <.0001).
Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported in 50.8% of patients in the niraparib arm and 19.3% of patients in the placebo arm.
Grade 3 or higher TEAEs that occurred more frequently in the niraparib arm than in the placebo arm included decreased neutrophil count (20.3% vs 8.0%), decreased platelet count (11.3% vs 1.1%), and anemia (14.7% vs 2.3%).
There was 1 case of treatment-related acute leukemia in the niraparib arm, which proved fatal.
“This is the first trial of PARP inhibitor maintenance therapy for ovarian cancer conducted in an Asian patient population and will support a change in clinical practice,” the study authors wrote. “Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.”
Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Wu XH, Zhu JQ, Yin RT, et al. Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): A randomized, double-blind, placebo-controlled phase III trial. Ann Oncol. 2021;32(4):512-521. doi:10.1016/j.annonc.2020.12.018