Search

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.)

Aim: This study aimed to investigate the real-world clinical practice of estrogen and progestogen prescriptions for menopausal women., Methods: Using a health care database in Japan, we conducted a cross-sectional study on estrogen prescriptions and detailed analyses of newly initiated estrogens and concomitant prescriptions of progestogens. Data between January 2005 and December 2021 were analyzed., Results: In 2021, the proportion of women aged 45-49 years receiving estrogens was 25.8 [95% confidence interval (CI): 25.3, 26.3] per 1000 women, while it was 6.4 [95% CI: 6.0, 6.7] for those aged ≥60 years. The prescription of estrogens gradually increased in women aged 50-59 years after 2009. In women without a history of hysterectomy, transdermal estradiol was the primary form of estrogens prescribed for ≥180 days, in women aged <60 years. The proportion of transdermal estradiol gradually increased each year, whereas that of oral-conjugated equine estrogens decreased. Among progestogen, the proportions of dydrogesterone and transdermal norethisterone acetate increased over time, while that of medroxyprogesterone acetate decreased. Approximately 30% of women prescribed estrogens for ≥180 days did not initiate progestogen concurrently. In women undergoing hysterectomy, progestogen was not initiated in >90% of cases, and transdermal estradiol was prescribed in approximately 80% of cases in 2021., Conclusions: This study reviewed the prescription of estrogens in menopausal women in Japan. A considerable number of women with a uterus are receiving estrogen therapy rather than estrogen-progestogen therapy (EPT), despite the guidelines recommending the use of EPT in these women., (© 2023 Japan Society of Obstetrics and Gynecology.)

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20-29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016-2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20-29 years also decreased from 256 cases to 135 cases during 2011-2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20-29 years during 2017-2022 (90.5%-64.7%, p = 0.05; Cochran-Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aim: Hormone replacement therapy (HRT) relieves menopausal syndromes but concerns regarding certain cancer risks remain. This study aimed to investigate cancer risks in perimenopausal women using HRT., Methods: Using a health care database in Japan, we compared breast cancer and other cancer risks in perimenopausal women who started HRT between January 2011 and October 2021 at age 45-54 years with that of women who did not use HRT. Women in the control group were selected by 1:4 exact matching on birth year, and followed from the same index time as their counterparts., Results: Data from 12 207 women in the exposure group and 48 828 age-matched women in the control group were analyzed. The median HRT duration was 16.1 (interquartile range, 9.9-28.0) months. Breast cancer risk was lower in the HRT group (adjusted hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.54-0.82). When stratified by age, breast cancer risk was lower in the HRT group who started HRT at age 45-49 years (adjusted HR, 0.54; 95% CI, 0.40-0.72). Estrogen-major HRT accounted for approximately one-third of HRT and uterine corpus cancer risk was increased in estrogen-major HRT (adjusted HR, 2.44; 95% CI, 1.56-3.81)., Conclusions: Breast cancer risk in women starting HRT between 45 and 49 years is lower than that in the average population; this finding might be susceptible to unmeasured factors such as early menopause among HRT recipients. Unopposed estrogen therapy accounts for considerable proportion of HRT in Japan and it increases uterine corpus cancer., (© 2023 Japan Society of Obstetrics and Gynecology.)

Background: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy., Methods: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death., Results: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively., Conclusions: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer., Materials and Methods: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m 2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m 2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety., Results: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks., Conclusion: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer., Competing Interests: Junzo HamanishiResearch Funding: MSD, Ono Pharmaceutical, Sumitomo Dainippon Pharma Noriyuki KatsumataConsulting or Advisory Role: Nippon Zoki Pharmaceutical Co, Ltd Kimio UshijimaHonoraria: AstraZeneca, Chugai Pharmaceutical, Takeda, Nippon Kayaku, MSD, Kaken Pharmaceutical, Kyowa Kirin InternationalResearch Funding: AstraZeneca, Chugai Pharmaceutical, Takeda, Kaken Pharmaceutical, Nippon Kayaku, Mochida Pharmaceutical Co, Ltd, Taiho Pharmaceutical, Eisai, Ono Pharmaceutical, AbbVie, MSD Tadashi KimuraHonoraria: Nobelpharma Co, Ltd, GE Healthcare Japan, Mochida Pharmaceutical Co, Ltd, Chugai Pharmaceutical Co, Ltd, Bayer Pharmaceuticals, Aska PharmaceuticalConsulting or Advisory Role: Fermata Pharma, Rohto PharmaceuticalResearch Funding: Fuji Pharma, Nippon Shinyaku, Takeda Yakuhin, Taihou Yakuhin, Mochida Pharmaceutical Co, Ltd, Nihon Seiyaku, Zeria Pharmaceutical Koji MatsumotoHonoraria: Chugai Pharmaceutical, AstraZeneca, Kyowa Hakko Kirin, Eisai, MSD K.K., Eli Lilly Japan K.K., Taiho Oncology, AbbVie, PfizerResearch Funding: Ono Pharmaceutical, MSD, AstraZeneca, Novartis, Chugai Pharmaceutical, Eisai Kimihiko ItoHonoraria: AstraZenecaConsulting or Advisory Role: AstraZeneca, AbbVie, Nippon Shinyaku, TerumoUncompensated Relationships: Kansai Clinical Oncology Group Hidemichi WatariHonoraria: MSD K.K., Tsumura & Co, AstraZeneca, Aska Pharmaceutical Co, Ltd, Terumo, Bayer Yakuhin, Kaken Pharmaceutical, Mochida Pharmaceutical Co, Ltd, Daiichi Sankyo/UCB Japan, Chugai Pharmaceutical, TakedaConsulting or Advisory Role: Decision Resources Group Japan, Kaken Pharmaceutical, Chugai PharmaceuticalResearch Funding: Hokkaido Welfare Federation of Agricultural Cooperatives, Kaken Pharmaceutical, Mochida Pharmaceutical Co, Ltd, Taiho Pharmaceutical, Chugai Pharmaceutical, Hokkaido Cancer Society, TakedaOther Relationship: T-PEC Nobutaka TakahashiHonoraria: Olympus, Ethicon/Johnson & Johnson, Intuitive Surgical, Kaken Pharmaceutical Kosei HasegawaHonoraria: MSD K.K., Daiichi Sankyo, Bayer Yakuhin, Bristol-Myers Squibb K.K., Chugai Pharmaceutical, AstraZeneca, EisaiConsulting or Advisory Role: MSD K.K., Kaken PharmaceuticalResearch Funding: Ono Pharmaceutical, Daiichi Sankyo, Takeda Kan YonemoriHonoraria: Eisai, Pfizer, AstraZeneca, Novartis, Taiho PharmaceuticalConsulting or Advisory Role: Chugai Pharmaceutical, Ono Pharmaceutical, Novartis, EisaiResearch Funding: Ono Pharmaceutical Kazuhiro TakeharaHonoraria: Takeda Pharmaceutical Company, AstraZeneca, Eisai, Chugai Pharmaceutical, MSD, Mochida Pharmaceutical Co, LtdResearch Funding: Chugai Pharmaceutical Hitoshi NiikuraHonoraria: Takeda Sari NakaoUncompensated Relationships: Japanese Gynecologic Oncology Group Toshiaki SaitoHonoraria: Nippon Kayaku, Kyowa Hakko Kirin, Eisai, Kaken Pharmaceutical CompanyResearch Funding: Chugai Pharmaceutical, Taiho Pharmaceutical Takayuki EnomotoHonoraria: AstraZeneca, MSD, Chugai Pharmaceutical Satoru NagaseHonoraria: Chugai Pharmaceutical, AstraZeneca Aikou OkamotoHonoraria: AstraZeneca K.K., MSD, Chugai Pharmaceutical, TakedaConsulting or Advisory Role: AstraZeneca K.K., Chugai PharmaceuticalSpeakers' Bureau: AstraZeneca K.K.Research Funding: Kissei Pharmaceutical, Meiji Holdings, Pfizer, Fuji Pharma, Taiho Pharmaceutical, Kaken Pharmaceutical, Chugai Pharmaceutical, Tsumura & Co, Daiichi Sankyo Company, Ltd, Shinnihonseiyaku, Mochida Pharmaceutical Co, Ltd, Aska Pharmaceutical Co, Ltd, Takeda, Terumo Yoshito TeraiResearch Funding: Ethicon/Johnson & Johnson, MSD, Covidien, Terumo, Daiichi Sankyo/UCB Japan, Chugai Pharmaceutical, Taiho Pharmaceutical Akira TakazawaEmployment: Ono Pharmaceutical Yusuke TakahashiEmployment: Ono PharmaceuticalStock and Other Ownership Interests: Ono Pharmaceutical Yoshinobu NambaEmployment: Ono PharmaceuticalHonoraria: Boehringer Ingelheim Daisuke AokiHonoraria: AstraZeneca K.K., MSD K.K., Takeda, Chugai Pharmaceutical, Myriad GeneticsConsulting or Advisory Role: Takeda, MSD K.K., AstraZeneca K.K.Speakers' Bureau: AstraZeneca K.K., Takeda Keiichi FujiwaraHonoraria: Kyowa Hakko Kirin, Zeria Pharmaceutical, Nippon Kayaku, Chugai Pharmaceutical, Eisai, Taiho Pharmaceutical, Daiichi Sankyo, Ono Pharmaceutical, TakedaConsulting or Advisory Role: AstraZeneca, MSD, Taiho Pharmaceutical, Eisai, Takeda, Genmab, AbbVie, Pfizer, NanoCarrierResearch Funding: Eisai, Kaken Pharmaceutical, Chugai Pharmaceutical, Shionogi, ImmunoGen, ONCOtherapeutics, AstraZeneca, Eli Lilly, Zeria Pharmaceutical, Ono Pharmaceutical, MSD, Genmab, Regeneron, Merck KGaA, Ono PharmaceuticalTravel, Accommodations, Expenses: Pfizer, AbbVie, MSDNo other potential conflicts of interest were reported.

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., 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.)

Background: The development of perforations or fistulas in the Gastrointestinal (GI) tract or genitourinary (GU) system is a serious adverse effect of bevacizumab. The aim of this study was to investigate the incidences of these GI/GU events as well as their association with previous radiotherapy (RT) in Japanese women with cervical cancer., Methods: We conducted a written questionnaire survey among 14 gynecological institutions belonging to the Oncology Research Committee of the Obstetrical and Gynecological Society of Kinki District, Japan. The severity of GI/GU events was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. All data were extracted from survey responses and maintained in an Excel spreadsheet and summarized using descriptive statistics., Results: The information of 224 Japanese women with cervical cancer (152 recurrent and 72 advanced) who were treated with bevacizumab-containing chemotherapy was collected from 14 institutions. Of these, 65% had been previously treated with RT. GI/GU events of any grade developed in 25 (11.2%) patients, leading directly to death in 3 (1.3%) patients. When compared, the incidence of GI/GU events was higher in recurrent disease patients than in advanced disease patients (13.8% vs 5.6%, p = 0.0728). When examined according to the history of RT, the incidence of GI/GU events was greater in patients with a history of RT than in those without (14.5% vs 5.1%, p = 0.044)., Conclusion: More than 10% of patients experience GI/GU events during or after receiving bevacizumab-containing chemotherapies. Prior RT is a risk factor for bevacizumab-associated GI/GU events.

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., (Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)