Objective: Epithelial ovarian cancer (EOC) is the leading cause of female mortality in gynecologic malignancies, with a rising incidence in Japan. This study aimed to validate the treatment patterns and safety of niraparib as maintenance therapy for EOC following initial chemotherapy in clinical practice in Japan. Methods: Leveraging claims data between April 2008 and December 2022, this descriptive study comprised EOC-diagnosed patients receiving initial platinum-based chemotherapy, debulking surgery, and niraparib as maintenance therapy. Patient characteristics, prescription status, transfusion details, and laboratory data were assessed and reported as summary statistics and frequencies. Results: Among 291 patients, the median age was 64.0 years and 94.5% received a 200-mg daily dose of niraparib. At week 12, 78.7% (229/291) continued niraparib treatment, 21.3% (62/291) discontinued, and 52.2% (152/291) required treatment interruptions. Of the 62 patients who discontinued treatment, 27 patients initiated subsequent EOC treatment within 12 weeks following niraparib discontinuation. Blood transfusions were needed in 10.3% (30/291), and of 55 patients with available laboratory data, 61.8% (34/55) had decreased platelet count <100,000/µL, 25.5% (14/55) had decreased hemoglobin level <8 g/dL, and 22.7% (5/22) had decreased neutrophil count <1,000/µL, meeting the criteria for treatment interruption. Among those with thrombocytopenia, 88.2% (30/34) were able to either resume or continue treatment. Conclusion Niraparib demonstrated favorable tolerability in Japanese patients with advanced EOC, with effective management of thrombocytopenia through dose adjustments and supportive care, supporting its viability as post-chemotherapy maintenance therapy.

Objective: The standard dose for pegylated liposomal doxorubicin (PLD) is 50 mg/m2 every 4 weeks. While 40 mg/m2 has recently been used in clinical practice, evidence supporting this use remains lacking. Methods: This phase III randomized, non-inferiority study compared progressionfree survival (PFS) for patients with platinum-resistant ovarian carcinoma between an experimental arm (40 mg/m2 PLD) and a standard arm (50 mg/m2 PLD) until 10 courses, disease progression or unacceptable toxicity. Eligible patients had received ≤2 prior lines.Stratification was by performance status and PFS of prior chemotherapy (<3 months versus ≥3 months). The primary endpoint was PFS and secondary endpoints were overall survival (OS), toxicity profile, clinical response and tolerability. The total number of patients was 470. Results: The trial was prematurely closed due to slow recruitment, with 272 patients randomized to the experimental arm (n=137) and standard arm (n=135). Final analysis was performed with 234 deaths and 269 events for PFS. In the experimental arm vs. standard arm, median PFS was 4.0 months vs. 4.0 months (hazard ratio [HR]=1.065; 95% confidence interval [CI]=0.830–1.366) and median OS was 14.0 months vs. 14.0 months (HR=1.078; 95% CI=0.831–1.397). Hematologic toxicity and oral cavity mucositis (≥grade 2) were more frequent in the standard arm than in the experimental arm, but no difference was seen in ≥grade 2 hand-foot skin reaction. Conclusion Non-inferiority of 2 PLD dosing schedule was not confirmed because the trial was closed prematurely. However, recommendation of dose reduction of PLD should be based both on efficacy and safety.

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.
Carcinoma, Large Cell ; Carcinoma, Neuroendocrine ; Carcinoma, Small Cell ; Endometrial Neoplasms ; Endometrium ; Female ; Gynecology ; Japan ; Medical Oncology ; Multivariate Analysis ; Obstetrics ; Prognosis ; Retrospective Studies