Individualized starting dose of niraparib effective, well tolerated in Chinese patients with recurrent ovarian cancer

Individualized starting dose (ISD) of maintenance niraparib improves progression-free survival (PFS) vs placebo in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC), results of the NORA trial have shown.

According to the investigators, the PFS benefit of ISD niraparib is consistent with that of its fixed starting dose demonstrated in the NOVA trial, with an improved safety profile compared with the NOVA regimen. [Wu X et al, ESMO 2020, abstract LBA29]

“NORA is the first fully powered phase III randomized controlled trial assessing the effectiveness and safety of a poly(ADP-ribose) polymerase [PARP] inhibitor in Chinese patients with PSROC,” said NORA principal investigator, Dr Xiaohu Wu of the Gynaecologic Oncology Department of Fudan University Shanghai Cancer Centre, China. “Our findings support the use of ISD of niraparib, which should be considered as standard of care for maintenance therapy of ovarian cancer.”

A former retrospective analysis showed that ISD based on body weight and platelet count measured at baseline may improve the safety profile of niraparib without compromising efficacy. [Ann Oncol 2018;29:1784-1792] A phase I study of niraparib showed comparable pharmacokinetic profile between Chinese and Caucasian patients with recurrent ovarian cancer. [Oncologist 2020;25:19-e10]

The NORA study included 265 Chinese patients (median age, 54.0 years; median body weight, 61 kg) with PSROC who had either germline BRCA (gBRCA) mutation or high-grade serous histologic features and a complete or partial response to previous platinum-based therapy. The patients were randomized (2:1) to receive oral niraparib (n=177) or placebo (n=88). The starting dose was individualized (200 mg QD for patients with a baseline body weight <77 Kg and a platelet count <150,000/μL, or otherwise 300 mg QD as the standard starting dose) following a protocol amendment after 11 patients had received a fixed starting dose of 300 mg.

At baseline, 155 patients were started on olaparib 200 mg QD, 22 patients received niraparib 300 mg QD (11 patients each before and after protocol amendment, while 88 patients received placebo.

Niraparib demonstrated a 68 percent reduction in risk of disease progression or death vs placebo in the intention-to-treat population (ITT) as determined by blinded independent central review (median PFS, 18.3 months vs 5.4 months; hazard ratio [HR], 0.32; 95 percent confidence interval [Cl], 0.23 to 0.45; p<0.0001).

Subgroup analysis revealed a PFS benefit of niraparib vs placebo regardless of gBRCAmut status (gBCRAmut: median PFS, not estimable [NR] vs 5.5 months; HR, 0.22; 95 percent CI, 0.12 to 0.39; p<0.0001) (non-gBRCAmut: median PFS, 11.1 months vs 3.9 months; HR, 0.40; 95 percent CI, 0.26 to 0.61; p<0.0001). “The PFS benefit is consistent with results of the NOVA trial in patients with gBRCAmut tumours [HR, 0.27; 95 percent CI, 0.17 to 0.41] and non-gBRCAmut tumours [HR, 0.45; 95 percent CI, 0.34 to 0.61],” said Xu.

In addition, niraparib significantly extended the chemotherapy-free interval (CFI) (median, 18.5 months vs 9.7 months; HR, 0.34; 95 percent CI, 0.24 to 0.48; p<0.0001) and time to first subsequent therapy (TFST) (median, 16.7 months vs 7.7 months; HR, 0.35; 95 percent CI, 0.25 to 0.50; p<0.0001) vs placebo.

Overall, grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 50.8 percent of patients treated with niraparib vs 19.3 percent of those who received placebo. Grade 3/4 haematological TEAEs were more common with niraparib vs placebo (decreased neutrophil count, 20.3 percent vs 8.0 for placebo) (anaemia, 14.7 percent vs 2.3 percent) (decreased platelet count, 11.3 vs 1.1 percent).

“However, ISD of niraparib demonstrated an improved safety profile compared with the fixed starting dose evaluated in the NOVA trial, particularly in terms of haematological toxicities,” said Xu. “In NOVA, grade 3/4 TEAEs of anaemia occurred in 25.3 percent of patients in the niraparib arm vs no patients in the placebo arm, while neutropenia occurred in 19.6 percent 1.7 percent of patients and thrombocytopenia occurred in 33.8 percent vs 0.6 percent of patients.”