The phase 3 NORA clinical trial has confirmed that an individualized starting dose of niraparib (Zejula) significantly improves outcomes in patients with platinum-sensitive, recurrent ovarian cancer.
The findings, presented at the European Society for Medical Oncology Virtual Congress 2020 by Xiaohua Wu, MD, Director, Gynecologic Oncology, Fudan University Shanghai Cancer Center, China, validated data from an earlier retrospective analysis of the NOVA phase 3 clinical trial, in which an individualized starting dose based on baseline body weight and platelet count preserved the efficacy of niraparib given at a fixed starting dose of 300 mg once daily while improving safety.
Based on the findings from NORA, “an individualized starting dose of niraparib is effective and safe and should be considered the standard clinical practice for the maintenance therapy of patients with ovarian cancer,” said Dr Wu.
In NOVA, patients with a low body weight (<77 kg) or low platelet count (<150,000/μL) were found to benefit from a 200-mg starting dose of niraparib on the end point of progression-free survival (PFS).
The NORA trial therefore was conducted with an amended protocol to assess prospectively the efficacy and safety of a 200-mg starting dose of niraparib in those patients with a body weight <77 kg or platelet count <150,000/μL.
NORA included 265 patients with platinum-sensitive, recurrent ovarian cancer who were treated at 1 of 32 hospitals in China.
Patients had either germline BRCA mutation or high-grade serous histologic features and exhibited complete or partial response after completing their last round of platinum therapy. They were randomized 2:1 to receive niraparib (N = 177) or placebo (N = 88) once daily. The primary end point was PFS.
Of the 265 total patients, the first 16 received the fixed starting dose of 300 mg, after which the protocol was amended such that patients with a baseline body weight <77 kg or a platelet count <150,000/μL received 200 mg (N = 235), while other patients received 300 mg (N = 14).
At data cutoff, 43% of patients in the niraparib group and 13% of patients in the placebo group were still receiving treatment. The median duration of follow-up at the time of data cutoff was 15.8 months.
The median PFS in the intent-to-treat population was 18.3 months in patients randomized to niraparib versus 5.4 months in those assigned to placebo, corresponding to a hazard ratio (HR) of 0.32 (P <.0001).
“Prespecified subgroup analysis revealed that the PFS benefit of niraparib was consistent among all patient subgroups,” including by BRCA mutation status, said Dr Wu.
Consistent with the primary end point, niraparib improved the chemotherapy-free interval (median, 18.5 vs 9.7 months; HR, 0.34; P <.0001) and time to first subsequent therapy (median, 16.7 vs 7.7 months; HR, 0.35; P <.0001) compared with placebo. At the time of data cutoff, overall survival data were immature.
“[Using] the individualized dosing regimen adopted in the NORA study, niraparib treatment was generally well tolerated, with no new safety signals identified,” Dr Wu said. Overall, most adverse events were grade 1 or 2 and could be managed with dose modification.
Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 50.8% of patients in the niraparib arm versus 19.3% of patients in the placebo arm. TEAEs led to treatment discontinuation in 4.0% of the niraparib arm and 5.7% of the placebo arm.
The most common TEAEs grade ≥3 in the niraparib arm were decreased neutrophil count (20.3% vs 8.0% for placebo), anemia (14.7% vs 2.3% for placebo), decreased platelet count (11.3% vs 1.1% for placebo), and decreased white blood cell count (7.3% vs 2.3% for placebo).