Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer

Abstract

Objective To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs. Results Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%. Conclusion Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified. Trial Registration ClinicalTrials.gov Identifier: NCT03759600

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

“…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. 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 20 .…”

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.…”