Evaluation of an individualized starting dose of niraparib in the PRIMA/ENGOT-OV26/GOG-3012 study

Objective The PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016) was amended to prospectively evaluate the safety/efficacy of an individualized starting dose (ISD) of niraparib compared to the approved fixed starting dose (FSD) regimen.

Materials and methods This double-blind, placebo-controlled, phase 3 study randomized 733 patients with newly-diagnosed advanced OC who responded to first-line platinum-based chemotherapy. The protocol was amended from a 300-mg FSD for all patients to an ISD regimen: 200 mg QD in patients with bodyweight < 77 kg and/or platelet count < 150,000/µL or 300 mg QD in all others. Exposure, efficacy, and safety data were compared between the regimens.

Results Patients who received a FSD (0.59; 95% CI, 0.46-0.76) or ISD (0.69; 95% CI, 0.48-0.98) showed similar improvements in progression-free survival compared to placebo. An interaction test showed no treatment difference between ISD and FSD at the pre-specified 0.10 significance level (p=0.30). Medians for dose intensity and relative dose intensity were similar between the subgroups. The safety profile among patients in the niraparib arm (n=484), including grade ≥3 hematologic toxicities, improved with the incorporation of the ISD regimen (Table)

Grade ≥3 hematologic toxicities in patients who received a fixed starting dose (FSD) vs an individualized starting dose (ISD)

Grade ≥3 hematologic toxicities, n (%)	FSD Niraparib n = 315	ISD Niraparib n = 169	FSD Placebo n = 158	ISD Placebo n = 86
Thrombocytopenia event	152 (48)	36 (21)	0	1 (1)
Anemia event	112 (36)	38 (22)	3 (2)	1 (1)
Neutropenia event	75 (24)	25 (15)	2 (1)	1 (1)

Summary ISD in the first-line maintenance setting provided comparable efficacy to FSD while reducing the risk of hematologic toxicities.

Sponsor GlaxoSmithKline, Waltham, MA, USA

Publication History

Article published online:
07 October 2020