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Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer., Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1 / 2 mutation ( BRCA1 / 2 mut) status detected by ctDNA sequencing., Results: Baseline samples were available from 23 BRCA1 / 2 mut-positive patients and 33 BRCA1/2 mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium , Roseburia , Dialister , Butyricicoccus , and Bilophila for BRCA1/2 mut-positive patients and Phascolarctobacterium for BRCA1/2 mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2 mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2 mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11-0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016)., Conclusion: High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2 mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research., Competing Interests: Mika Okazawa-Sakai declares no competing interests. Shunsuke A. Sakai declares no competing interests. Ichinosuke Hyodo reports advisory roles for Asahi-Kasei, Ono, Taiho, Chugai, and Eisai Pharmaceutical Companies. Satoshi Horasawa declares no competing interests. Kentaro Sawada declares no competing interests. Takao Fujisawa reports honoraria from Amelieff Co. Ltd. Yasuko Yamamoto declares no competing interests. Shogen Boku reports honoraria from Nippon Kayaku Co., Ltd., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol-Myers Squibb Japan, and MSD. Yoh Hayasaki declares no competing interests. Masanori Isobe declares no competing interests. Daisuke Shintani declares no competing interests. Kosei Hasegawa reports honoraria from AstraZeneca, GSK, MSD, and Takeda; advisory role for GSK, MSD, and Takeda; research grants from MSD. Tomomi Egawa-Takata declares no competing interests. Kimihiko Ito reports honoraria from AstraZeneca. Kei Ihira declares no competing interests. Hidemichi Watari reports honoraria from AstraZeneca, Takeda, MSD, and Chugai. Kazuhiro Takehara reports honoraria from AstraZeneca, Takeda, MSD, Chugai, Eisai, and Sanofi. Hiroshi Yagi declares no competing interests. Kiyoko Kato declares no competing interests. Tatsuyuki Chiyoda reports research grants from Takeda Pharmaceutical Company. Kenichi Harano reports honoraria from AstraZeneca, Chugai, Eizai, MSD, Taiho and Takeda, and advisory roles for AstraZeneca, Chugai, Eizai, Taiho and Takeda. Yoshiaki Nakamura declares advisory role from Guardant Health Pte Ltd., Natera, Inc., Roche Ltd., Seagen, Inc., Premo Partners, Inc., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Exact Sciences Corporation, Gilead Sciences, Inc.; speakers' bureau from Guardant Health Pte Ltd., MSD K.K., Eisai Co., Ltd., Zeria Pharmaceutical Co., Ltd., Miyarisan Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., CareNet, Inc., Hisamitsu Pharmaceutical Co., Inc., Taiho Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Becton, Dickinson and Company, Guardant Health Japan Corp; research funding from Seagen, Inc., Genomedia Inc., Guardant Health AMEA, Inc., Guardant Health, Inc., Tempus Labs, Inc., Roche Diagnostics K.K., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd. Riu Yamashita declares no competing interests. Takayuki Yoshino reports honoraria from Chugai Pharma, Takeda Pharma, Merck, Bayer Yakuhin, Ono Pharmaceutical and MSD K. K.; consulting fees from Sumitomo Corp.; and research grants from Amgen, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, FALCO Biosystems, Genomedia Inc., Medical & Biological Laboratories, Merus N.V., Molecular Health, MSD, Nippon Boehringer Ingelheim, Ono, Pfizer, Roche Diagnostics, Sanofi, Sysmex, Taiho and Takeda. Daisuke Aoki reports honoraria from AstraZeneca, Takeda, MSD, Chugai, and Myriad Genetics., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer., Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs)., Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively., Conclusion: The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified., Trial Registration: ClinicalTrials.gov Identifier: NCT03759600., Competing Interests: Daisuke Aoki declares the receipt of consulting fees from AstraZeneca, Chugai, MSD, and Takeda Pharmaceutical Company Ltd, and honoraria from AstraZeneca, Chugai, MSD, Myriad Genetics, and Takeda Pharmaceutical Company Ltd. Tsutomu Tabata declares the receipt of lecture fees from AstraZeneca, Chugai, and Takeda Pharmaceutical Company Ltd. Satoshi Yanagida, Toshiaki Nakamura and Hidekatsu Nakai declare the receipt of lecture fees from Takeda Pharmaceutical Company Ltd. Kenichi Harano declares the receipt of grants from AstraZeneca, Chugai, Daiichi Sankyo, MSD, and Takeda Pharmaceutical Company Ltd, and speaker fees from Astra Zeneca, Chugai, Eisai, MSD, Taiho, and Takeda Pharmaceutical Company Ltd. Kenichi Harano also declares an advisory role for AstraZeneca, Chugai, Taiho and Takeda Pharmaceutical Company Ltd, and receipt of institutional research funding from Takeda Pharmaceutical Company Ltd. Kosei Hasegawa declares the receipt of research grants from Daiichi Sankyo, Eisai, MSD, and Takeda Pharmaceutical Company Ltd, honoraria from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Genmab, Kaken, Kyowa Kirin, MSD, Sanofi, and Takeda Pharmaceutical Company Ltd, and travel expenses from Regeneron. Kosei Hasegawa is also on the advisory board of Chugai, Eisai, Genmab, MSD, Roche, Sanofi, and Takeda Pharmaceutical Company Ltd. Shinichi Komiyama declares the receipt of consulting fees from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, and MSD, and honoraria from AstraZeneca, Chugai, Eisai, and Takeda Pharmaceutical Company Ltd. Kazuhiro Takehara declares the receipt of speaker bureaus fees from AstraZeneca, MSD, and Takeda Pharmaceutical Company Ltd, and manuscript writing fees from MSD. Yoichi Kase and Ai Kato are employees of, and hold stocks in Takeda Pharmaceutical Company Ltd. Shuuji Sumino and Junpei Soeda are employees of Takeda Pharmaceutical Company Ltd. Ajit Suri is an employee of Millennium Pharmaceuticals, part of Takeda, and holds stocks in Takeda Pharmaceutical Company Ltd. Aikou Okamoto declares the receipt of honoraria from ASKA Pharmaceutical Co., Ltd, AstraZeneca, Bayer Holding Ltd, Chugai, Covidien Japan Inc., Eisai, Fuji Pharma Co., Ltd, Johnson & Johnson K.K., Kaken Pharmaceutical Co., Ltd, Kissei Pharmaceutical Co., Ltd, MSD, Mochida Pharmaceutical Co., Ltd, Myriad Genetics G.K., Otsuka Pharmaceutical Co., Ltd, Sanofi, Takeda Pharmaceutical Company Ltd, and Zeria Pharmaceutical Co., Ltd. Aikou Okamoto also declares the receipt of institutional grants from ASKA Pharmaceutical Co., Ltd, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Fuji Pharma Co., Ltd, Gyne Mom Co., Ltd, Kaken Pharmaceutical Co., Ltd, Linical Co., Ltd, Meiji Holdings Co., Ltd, Merck BioPharma Japan, Mochida Pharmaceutical Co., Ltd, MSD, Nippon Shinyaku Co., Ltd, Taiho Pharmaceutical Co., Ltd, and Tsumura & Co. Other authors have no conflict of interest to disclose., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer., Methods: This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms "thrombocytopenia" and "platelet count decreased") occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival., Results: Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56-1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6-26.7) months., Conclusion: Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients., Trial Registration: ClinicalTrials.gov Identifier: NCT03759587., Competing Interests: Kosei Hasegawa declares the receipt of research grants from Daiichi Sankyo, Eisai, MSD, and Takeda Pharmaceuticals Company Ltd, honoraria from AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Genmab, Kaken, Kyowa Kirin, MSD, Sanofi, and Takeda Pharmaceuticals Company Ltd, and travel expenses from Regeneron. Kosei Hasegawa is also on the advisory board of Chugai, Eisai, Genmab, MSD, Roche, Sanofi, and Takeda Pharmaceuticals Company Ltd. Shoji Nagao declares the receipt of grants from AstraZeneca, consulting fees from AstraZeneca, and honoraria from AstraZeneca, Chugai, Eisai, MSD, and Takeda Pharmaceuticals Company Ltd. Kazuhiro Takehara declares the receipt of speaker bureaus fees from AstraZeneca, MSD, and Takeda Pharmaceutical Company Ltd, and manuscript writing fees from MSD. Hidekatsu Nakai and Hidemichi Watari declare the receipt of lecture fees from Takeda Pharmaceutical Company Ltd. Shuuji Sumino is an employee of Takeda Pharmaceutical Company Ltd. Yoichi Kase and Ai Kato are employees of, and hold stocks in Takeda Pharmaceutical Company Ltd. Ajit Suri is an employee of Millennium Pharmaceuticals, part of Takeda Pharmaceutical Company Ltd, and holds stocks in Takeda Pharmaceutical Company Ltd. Other authors have no conflict of interest to disclose., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: This study aimed to determine whether the number of resected pelvic lymph nodes (PLNs) affects the prognosis of endometrial cancer (EC) patients at post-operative risk of recurrence., Methods: JGOG2043 was a randomized controlled trial to assess the efficacy of three chemotherapeutic regimens as adjuvant therapy in EC patients with post-operative recurrent risk. A retrospective analysis was conducted on 250 patients who underwent pelvic lymphadenectomy alone in JGOG2043. The number of resected and positive nodes and other clinicopathologic risk factors for survival were retrieved., Results: There were 83 patients in the group with less than 20 PLNs removed (group A), while 167 patients had 20 or more PLNs removed (group B). There was no significant difference in patients' backgrounds between the two groups, and the rate of lymph node metastasis was not significantly different. There was a trend toward fewer pelvic recurrences in group B compared with group A (3.5% vs. 9.6%; p=0.050). Although Kaplan-Meier analysis showed no statistically significant difference in survival rates between the two groups (5-year overall survival [OS]=90.3% vs. 84.3%; p=0.199), multivariate analysis revealed that resection of 20 or more nodes is one of the independent prognostic factors (hazard ratio=0.49; 95% confidence interval=0.24-0.99; p=0.048), as well as surgical stage, high-risk histology, and advanced age for OS., Conclusion: Resection of 20 or more PLNs was associated with improved pelvic control and better survival outcomes in EC patients at risk of recurrence who underwent pelvic lymphadenectomy alone and were treated with adjuvant chemotherapy., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: Fertility preserving therapy using medroxyprogesterone acetate (MPA) is an important option for young patients with endometrial cancer or atypical endometrial hyperplasia (AEH). However, the effectiveness and feasibility of repeated MPA therapy for patients with intrauterine recurrence following initial MPA therapy is controversial. Only a few single-institution retrospective studies have been conducted on repeated MPA therapy, therefore, multicenter prospective studies for repeated MPA therapy are highly needed. The aim of this study is to assess whether repeated MPA therapy is effective and feasible for patients with intrauterine recurrence following initial MPA therapy., Methods: This is a prospective, single-arm, a multicenter phase II trial on repeated MPA therapy for intrauterine recurrence following fertility-preserving therapy for AEH or stage IA (the International Federation of Gynecology and Obstetrics [FIGO] 2008) non-myoinvasive endometrioid carcinoma grade 1. Patients are treated with oral MPA (500-600 mg/day). Pathologically assessment via dilation and curettage will be performed every 2 months until complete response. The major inclusion criteria are 1) intrauterine recurrence of AEH or stage IA (FIGO 2008) endometrioid carcinoma grade 1 without myometrial invasion or extrauterine spread confirmed by imaging tests after complete remission with the previous MPA therapy. 2) The number of recurrences should be up to twice. 3) histologically diagnosed as AEH or endometrioid carcinoma grade 1, 4) 20-42 years of age, and 5) strong desire and consent for fertility-sparing treatment. The primary endpoint is 2-year recurrence-free survival rate. A total of 115 patients will be enrolled from multiple institutions in Japan and Korea within 4 years and followed up for 2 years., Trial Registration: Japan Registry of Clinical Trials Identifier: jRCTs031200256., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: The practices pertaining to hereditary breast and ovarian cancer (HBOC) in Japan have been rapidly changing owing to the clinical development of poly(ADP-ribose) polymerase inhibitors, the increasing availability of companion diagnostics, and the broadened insurance coverage of HBOC management from April 2020. A questionnaire of gynecologic oncologists was conducted to understand the current status and to promote the widespread standardization of future HBOC management., Methods: A Google Form questionnaire was administered to the members of the Japan Society of Gynecologic Oncology. The survey consisted of 25 questions in 4 categories: respondent demographics, HBOC management experience, insurance coverage of HBOC management, and educational opportunities related to HBOC., Results: A total of 666 valid responses were received. Regarding the prevalence of HBOC practice, the majority of physicians responded in the negative and required human resources, information sharing and educational opportunities, and expanded insurance coverage to adopt and improve HBOC practice. Most physicians were not satisfied with the educational opportunities provided so far, and further expansion was desired. They remarked on the psychological burdens of many HBOC managements. Physicians reported these burdens could be alleviated by securing sufficient time to engage in HBOC management, creating easy-to-understand explanatory material for patients, collaboration with specialists in genetic medicine, and educational opportunities., Conclusion: Gynecologic oncologists in Japan are struggling to deal with psychological burdens in HBOC practice. To promote the clinical practice of HBOC management, there is an urgent need to strengthen human resources and improve educational opportunities, and expand insurance coverage for HBOC management., Competing Interests: Dr. Kobayashi reports grants and personal fees from Takeda Pharmaceutical Co., Ltd., personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd. Dr. Hirasawa reports personal fees from ACTmed Co. Ltd. Dr. Takehara reports personal fees from Takeda Pharmaceutical Co., Ltd. and AstraZeneca K.K. Dr. Aoki reports personal fees from Takeda Pharmaceutical Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K. The other authors have nothing to disclose., (© 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: To determine the safety and efficacy of dose-dense (dd) paclitaxel (PTX) and carboplatin (CBDCA) in treating advanced or recurrent endometrial cancer., Methods: Women aged 20-75 years with histologically confirmed endometrial cancer, the International Federation of Gynecology and Obstetrics (FIGO) stage III disease with some residual tumor, FIGO stage IV disease, recurrence after front-line curative treatment, or recurrence after second-line chemotherapy or radiotherapy were enrolled in this study. PTX (80 mg/m²) was administered intravenously (IV) to every participant on days 1, 8, and 15, and CBDCA (area under the curve of 5) was administered IV on day 1 once every 3 weeks until the disease progressed, unacceptable adverse events occurred, or consent was withdrawn. The primary endpoint was the response rate (RR), while the secondary endpoints were progression-free survival, overall survival, and adverse effects., Results: Forty-eight participants were enrolled, and 46 were eligible to receive treatment. The patients' median age was 61 years (range, 43-76 years). Twenty-two participants had experienced recurrence, and the remaining patients had primary advanced endometrial cancer. There were 10 cases of serous carcinoma, 3 cases of endometrioid carcinoma G3, 2 cases of carcinosarcoma, and 2 cases of clear-cell carcinoma according to histology. Twenty-nine participants (63.0%) received ≥6 cycles of chemotherapy. The RR (complete, 13 cases; partial, 20 cases) was 71.3% (95% confidence interval: 59.0%-84.5%)., Conclusion: The dd PTX with CBDCA is feasible and available as a treatment option for advanced or recurrent endometrial cancer., Trial Registration: UMIN Clinical Trials Registry Identifier: UMIN000017138., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)