Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer

Abstract

Objective The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. Methods Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients with platinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens. The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30 days after initial niraparib administration) was justified by the incidences of a global pivotal phase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematological adverse event of niraparib. The overall safety analysis examined other treatment-emergent adverse events (TEAEs). Results Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8–79.1) kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib 300 mg/day but this decreased in subsequent cycles (mean±standard deviation dose intensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration. Other common TEAEs included nausea, and decreased platelet or neutrophil counts. No progression-free or overall survival events occurred; only 1 of 4 response-evaluable patients had a post-baseline tumor assessment (stable disease). Conclusion The incidence of grade 3 or 4 thrombocytopenia-related events in Japanese ovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall, the safety profile was acceptable and consistent with the known safety profile and previous experience with niraparib. Trial Registration ClinicalTrials.gov Identifier: NCT03759587

Real-world Experience of Niraparib in Newly-diagnosed Epithelial Ovarian Cancer

“…Therefore, 200 mg niraparib was administered as the starting dose, but A/Es occurred in 50% of patients. In the case of a recurrent study with 300 mg as the starting dose (11,12), Asian patients did not show any significant differences in A/Es from patients in Western populations.…”

Increase in creatinine levels associated with niraparib maintenance therapy in ovarian cancer

“…Asians are generally smaller in stature than Europeans and Americans, which may lead to different AE profiles. In Japanese patients, increased creatine with niraparib was reported in 5.3% (1/19) in a prospective phase 2 study for platinum‐sensitive relapsed ovarian cancer 18 . Another phase 2 study for HRD‐positive ovarian cancer reported 20.0% (4/20), 19 but the number of cases were small in both trials.…”

“…In Japanese patients, increased creatine with niraparib was reported in 5.3% (1/19) in a prospective phase 2 study for platinum-sensitive relapsed ovarian cancer. 18 Another phase 2 study for HRDpositive ovarian cancer reported 20.0% (4/20), 19 but the number of cases were small in both trials. The NORA trial, which examined the efficacy and safety of niraparib maintenance therapy in platinum-sensitive recurrent ovarian cancer in Chinese subjects, included a large prospective data set for the same Asian population.…”

Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs

“…At the individualized starting dose, the dose was reduced in 65.7% of patients, and adverse events improved to 60.4% of Grade 3 or higher adverse events, including 21.3% related to thrombocytopenia, but the effect was somewhat inferior at HR 0.69 [ 28 ]. In Japan, niraparib-2001 and niraparib-2002 studies were conducted with a fixed starting dose for platinum-sensitive relapse cases [ 29 , 30 ], however, insurance approval was granted for individualized starting doses including first-line maintenance therapy.…”