Kazuhiro Takehara1, Takashi Matsumoto2, Junzo Hamanishi3, Kosei Hasegawa4, Motoki Matsuura5, Kiyonori Miura6, Shoji Nagao7, Hidekatsu Nakai8, Naotake Tanaka9, Hideki Tokunaga10, Kimio Ushijima11, Hidemichi Watari12, Yoshihito Yokoyama13, Yoichi Kase14, Shuuji Sumino15, Ajit Suri16, Hiroaki Itamochi17, Nobuhiro Takeshima18. 1. Department of Gynecologic Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 2. Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Matsuyama, Japan. 3. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 4. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Japan. 5. Department of Obstetrics and Gynecology, Sapporo Medical University, Sapporo, Japan. 6. Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan. 7. Department of Gynecologic Oncology, Hyogo Cancer Center, Akashi, Japan. 8. Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan. 9. Department of Gynecology, Chiba Cancer Center, Chiba, Japan. 10. Department of Obstetrics and Gynecology, Tohoku University, Sendai, Japan. 11. Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan. 12. Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 13. Department of Obstetrics and Gynecology, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan. 14. Oncology Clinical Research Department, Oncology Therapeutic Area Unit for Japan and Asia, Takeda Pharmaceutical Company Limited, Osaka, Japan. 15. Biostatistics, Japan Development Center, Takeda Pharmaceutical Company Limited, Osaka, Japan. 16. Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. 17. Department of Clinical Oncology, Iwate Medical University School of Medicine, Morioka, Japan. itamochi@iwate-med.ac.jp. 18. Department of Gynecology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
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.
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 cancerpatients 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.