Personalized starting doses of niraparib based on body weight and platelet count are associated with reductions in thrombocytopenia and other hematologic events.
Compared with the 300-mg fixed starting dose, an individualized starting dose of niraparib reduces the risk of hematologic toxicities while efficacy is maintained as first-line maintenance treatment of patients with recurrent ovarian cancer. Based on the phase 3 PRIMA study, the individualized starting dose was based on baseline body weight and platelet count and performed no differently than the fixed starting dose on the end point of progression-free survival. In addition, the dose was associated with fewer dose interruptions and reductions. The US Food and Drug Administration approved niraparib at a fixed starting dose of 300 mg daily for maintenance treatment.
Data were presented by investigators in a poster during this year’s 2020 American Society of Clinical Oncology Virtual Scientific Program. “Based on these results, an individualized starting dose is recommended for first-line maintenance treatment of patients with ovarian cancer,” concluded the investigators, led by Mansoor Raza Mirza, MD, Medical Director, Nordic Society of Gynecological Oncology-Clinical Trial Unit, and Chief Oncologist, Rigshospitalet Copenhagen University Hospital, Denmark.
PRIMA is a randomized double-blind study of niraparib versus placebo in patients with newly diagnosed advanced ovarian cancer who responded to first-line, platinum-based chemotherapy. A total of 733 patients who had a complete or partial response to first-line, platinum-based chemotherapy were randomized in a 2:1 ratio to niraparib at 300 mg daily or placebo. A post-hoc analysis of the phase 3 ENGOT-OV16/NOVA clinical trial identified baseline body weight and platelet count as predictors of high-grade thrombocytopenia and niraparib dose reductions, and the study protocol was amended. “Most thrombocytopenia events and dose adjustments occurred in the first 3 months, after which 200 mg was the most common dose,” said Dr Mirza and colleagues. “Retrospective analysis showed no impact of dose change on efficacy.”
In PRIMA, after the protocol was amended, patients randomized to niraparib were assigned to either 200 or 300 mg based on baseline body weight and platelet count. Patients with body weight ≥77 kg and a platelet count ≥150,000/µL were assigned to 300 mg daily of niraparib or placebo, whereas those with body weight <77 kg or a platelet count <150,000/µL were assigned to 200 mg daily of niraparib or placebo. After the protocol was amended, approximately 35% of the patients were enrolled. “The hazard ratio for efficacy for the 2 groups was similar at 0.59 for fixed starting dose and 0.69 for the individualized starting dose,” Dr Mirza said. “To determine if these results were statistically different, an interaction test was performed at the prespecified alpha of 0.1. The interaction was not statistically significant, which suggests that starting dose does not affect efficacy.” Based on Kaplan-Meier progression-free survival curves, there was no relationship between improved response in the niraparib arm and increased dose exposure, said Dr Mirza.
The rate of hematologic events was reduced by >50% with implementation of the individualized starting dose. The rate of thrombocytopenia was reduced from 48.3% in patients who received the fixed starting dose to 21.3% in those who received an individualized starting dose. Similar trends were observed in patients with anemia and neutropenia. The incidence of any grade ≥3 treatment-emergent adverse events was reduced from 75.9% to 60.4%.
Source: Mirza MR, et al. J Clin Oncol. 2020;38(15_suppl). Abstract 6050.