1.Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician’s choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer
Kan YONEMORI ; Keiichi FUJIWARA ; Kosei HASEGAWA ; Mayu YUNOKAWA ; Kimio USHIJIMA ; Shiro SUZUKI ; Ayumi SHIKAMA ; Shinichiro MINOBE ; Tomoka USAMI ; Jae-Weon KIM ; Byoung-Gie KIM ; Peng-Hui WANG ; Ting-Chang CHANG ; Keiko YAMAMOTO ; Shirong HAN ; Jodi MCKENZIE ; Robert J. ORLOWSKI ; Takuma MIURA ; Vicky MAKKER ; Yong Man KIM
Journal of Gynecologic Oncology 2024;35(2):e40-
Objective:
In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis.
Methods:
Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis.
Results:
Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively.
Conclusion
Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.
2.Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician’s choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer
Kan YONEMORI ; Keiichi FUJIWARA ; Kosei HASEGAWA ; Mayu YUNOKAWA ; Kimio USHIJIMA ; Shiro SUZUKI ; Ayumi SHIKAMA ; Shinichiro MINOBE ; Tomoka USAMI ; Jae-Weon KIM ; Byoung-Gie KIM ; Peng-Hui WANG ; Ting-Chang CHANG ; Keiko YAMAMOTO ; Shirong HAN ; Jodi MCKENZIE ; Robert J. ORLOWSKI ; Takuma MIURA ; Vicky MAKKER ; Yong Man KIM
Journal of Gynecologic Oncology 2024;35(2):e40-
Objective:
In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis.
Methods:
Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis.
Results:
Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively.
Conclusion
Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.
3.Analysis of East Asia subgroup in Study 309/KEYNOTE-775: lenvatinib plus pembrolizumab versus treatment of physician’s choice chemotherapy in patients with previously treated advanced or recurrent endometrial cancer
Kan YONEMORI ; Keiichi FUJIWARA ; Kosei HASEGAWA ; Mayu YUNOKAWA ; Kimio USHIJIMA ; Shiro SUZUKI ; Ayumi SHIKAMA ; Shinichiro MINOBE ; Tomoka USAMI ; Jae-Weon KIM ; Byoung-Gie KIM ; Peng-Hui WANG ; Ting-Chang CHANG ; Keiko YAMAMOTO ; Shirong HAN ; Jodi MCKENZIE ; Robert J. ORLOWSKI ; Takuma MIURA ; Vicky MAKKER ; Yong Man KIM
Journal of Gynecologic Oncology 2024;35(2):e40-
Objective:
In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis.
Methods:
Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis.
Results:
Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively.
Conclusion
Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.
4.A Case of Severe Respiratory Failure in a Patient with Sepsis From a Pressure Ulcer in Which Cooperation Among Many Professions Was Useful for Discharge From the Intensive Care Unit
Takashi INOUE ; Kei TAKAMURA ; Taku KOMORI ; Yuiko HASHINO ; Takatoshi SUZUKI ; Ai SHIWAKU ; Hajime KIKUCHI ; Makoto YAMAMOTO ; Yasuhiro ONO ; Keiko YAMAUCHI ; Tomomi OHMUKU ; Hidetoshi MISUMI ; Takiko MORI
Journal of the Japanese Association of Rural Medicine 2020;69(4):379-
A woman in her 60s was being treated for diabetes and hypertension but had impaired activities of daily living (ADL) due to severe obesity (150 kg). She was transported to the emergency department because of disturbance of consciousness in August 201X. Imaging findings showed decreased permeability of the whole right lung field. She was intubated and started on ceftriaxone plus levofloxacin for severe infection with respiratory failure. Erysipelothrix rhusiopathiae was detected in blood cultures, leading to a diagnosis of sepsis due to a large pressure ulcer on the posterior aspect of the thigh. We switched levofloxacin to clindamycin and continued medical treatment, and she was extubated on the 10th day of illness. However, type 2 respiratory failure was prolonged because of alveolar hypoventilation due to obesity and she required noninvasive positive pressure ventilation. Also, she had difficulty getting out of bed due to obesity, disuse syndrome, and pressure ulcer. Cooperation among staff from many professions, including respiratory nursing, intensive care nursing, wound, ostomy and continence nursing, physical therapy, and nutrition management, led to improvement of ADL and weight loss (to 109 kg), allowing her to be transferred out of the intensive care unit.
5.Evaluation of Community Health Medical Education:The Elderly Home Visit Program
Masayo KOJIMA ; Daisaku ASAI ; Daiki ISHIKAWA ; Yuki KIMURA ; Keiko AKASHI ; Hiroyasu AKATSU ; Hirotaka OHARA ; Yoshihiro KAWADE ; Kazunori KIMURA ; Masumi SUZUI ; Tadashi SUZUKI ; Tadahiro HASHITA ; Jyunichiro HAYANO ; Satona MURAKAMI ; Miyuki YAMAMOTO ; Kiyofumi ASAI
Medical Education 2019;48(4):221-235
Introduction: Research was carried out using a mixed method approach in order to evaluate the educational effects of medical students' visit of an elderly home.Methods: Focus group interviews were conducted with 5 medical students and 5 elderlies. All interviewees had experienced the visitation program more than three times. Self-administrative questionnaires were built based on the results of the focus group interview. The questionnaire was then distributed to medical students and elderlies who participated in the program.Results: A total of 84 medical students and 30 elderlies provided informed consent to participate in the study and returned the questionnaire. Nearly 70 percent of the students answered that they had gotten to know about the life of elderly people and sixty percent of the elderlies answered they had experienced some favorable changes after joining the program. While ninety percent of the elderly were satisfied with the program, only half of the students showed positive comments toward it.Discussion: To help all students participate in this program more actively, more organized planning is necessary so that students can have more chances to build communication skills and clarify their own objectives when visiting the elderly.
6.Validation of the Japanese Version of the STOP-Bang Test for the Risk Assessment of Obstructive Sleep Apnea Syndrome
Hideto OSHITA ; Hiroshi FUCHITA ; Noriaki ITO ; Misato SENOO ; Shoko ISOYAMA ; Yutaro YAMAMOTO ; Ayaka YOSHIDA ; Keiko OSAKI ; Kohei KAWASAKI ; Ken OKUSAKI
An Official Journal of the Japan Primary Care Association 2019;42(1):26-31
Objective: The objective of this study was to validate the Japanese version of the STOP-Bang test for risk assessment of obstructive sleep apnea syndrome (OSAS).Methods: We retrospectively evaluated inpatients who underwent nocturnal pulse oximetry for OSAS screening at the internal medical wards.Results: One hundred and forty-four subjects were included the study, and 57 subjects who had a 3% oxygen desaturation index ≥10/hr underwent polysomnography. Seventeen and 29 subjects were diagnosed with moderate and severe OSAS, respectively. According to the receiver operating characteristic (ROC) curve analysis, the STOP-Bang test had a higher diagnostic value using a cutoff of 30 kg/m2 for BMI than using a cutoff of 35 kg/m2. A STOP-Bang score of 3 or greater had a sensitivity of 95.7% and specificity of 42.9% for detecting moderate-to-severe OSAS.Conclusion: The STOP-Bang test is a simple and useful tool for the risk assessment of OSAS.
7.Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children's Health.
Machiko MINATOYA ; Sachiko ITOH ; Keiko YAMAZAKI ; Atsuko ARAKI ; Chihiro MIYASHITA ; Naomi TAMURA ; Jun YAMAMOTO ; Yu ONODA ; Kazuki OGASAWARA ; Toru MATSUMURA ; Reiko KISHI
Environmental Health and Preventive Medicine 2018;23(1):43-43
BACKGROUND:
Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates; however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age.
METHODS:
The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the first trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order, and age at SDQ completed.
RESULTS:
The median concentrations of BPA, MnBP, MiBP, MEHP, and MECPP, primary and secondary metabolites of phthalates, were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. MECPP level was associated with increase conduct problem risk (OR = 2.78, 95% CI 1.36-5.68) overall and the association remained after child sex stratification, and odds ratios were increased with wider confidence interval (OR = 2.85, 95% CI 1.07-7.57 for boys, OR = 4.04, 95% CI 1.31-12.5 for girls, respectively). BPA, ∑DBP (MnBP + MiBP), and ∑DEHP (MEHP+MECPP) levels were not associated with any of the child behavioral problems.
CONCLUSIONS
Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age but suggested possible association between MECPP levels and increased risk of conduct problems.
Adult
;
Age Factors
;
Benzhydryl Compounds
;
blood
;
Child, Preschool
;
Environmental Exposure
;
analysis
;
Female
;
Humans
;
Male
;
Phenols
;
blood
;
Phthalic Acids
;
blood
;
Pregnancy
;
Prenatal Exposure Delayed Effects
;
epidemiology
;
Problem Behavior
;
Smoking
;
epidemiology
;
Socioeconomic Factors
8.Report of Effect on the Medical Education of the Guidebook about the Behaviors of Physicians on the Death Pronouncement
Akihiko Kusakabe ; Jyunko Nozato ; Kazue Hirano ; Naohiro Saitou ; Keiko Ikenaga ; Hukiko Mikan ; Takaomi Kessoku ; Tetuya Matuura ; Asuka Yoshimi ; Akemi Naitou ; Masato Okita ; Masahiko Inamori ; Yuuji Yamamoto ; Tatsuya Morita
Palliative Care Research 2017;12(1):906-910
The experience at the time of a patient’s death can affect the mental health of bereaved families. Performing death pronouncements is an important skill for end-of-life care. However, almost no educational content regarding death pronouncements is presently included in medical educational programs. We have created a guidebook for “Physician behavior at the time of death pronouncement” based on the results of a questionnaire given to the families of deceased patients that included several items related to this topic. The purpose of this research was to investigate the educational effect of using this guidebook. The guidebook was given to 4th-year medical students attending the Yokohama City University School of Medicine. A survey was then conducted to assess evaluations of self-practice and feelings of difficulty at the time of making death pronouncements both before and after the class. Among the 39 students who provided valid responses, the majority (89.5%) indicated that they had difficulty with the item regarding “the specific method of death pronouncement.” A significant improvement was observed between the responses obtained before and those obtained after the class. We concluded that our guidebook for physician behavior at the time of death pronouncement might be useful for the education of medical students.
9.A Case of Primary Cutaneous Gamma-Delta T-Cell Lymphoma with Pautrier Microabscess.
Kohei KATO ; Takeshi NAMIKI ; Makiko UENO ; Madoka IIKAWA ; Shown TOKORO ; Aya NISHIZAWA ; Kouhei YAMAMOTO ; Keiko MIURA ; Hiroo YOKOZEKI
Annals of Dermatology 2017;29(2):229-232
No abstract available.
Lymphoma, T-Cell*
;
T-Lymphocytes*
10.A blended learning program providing core competency in clinical research
Naoki Kakudate ; Yukio Tsugihashi ; Yoko Yokoyama ; Yosuke Yamamoto ; Hiroki Mishina ; Fumiaki Nakamura ; Norio Fukumori ; Misa Takegami ; Shinya Ohno ; Keiko Sato ; Takafumi Wakita ; Kazuhiro Watanabe ; Takuhiro Yamaguchi ; Shunichi Fukuhara
Medical Education 2012;43(3):205-210
In Japan, few health care professionals have a basic understanding(core competency)of the design of clinical research and statistical analysis. We developed a blended distance–learning program comprising face–to–face lectures with e–learning for busy health care professionals who work in the clinical settings to achieve core competency in clinical research. The purpose of this study was to examine the educational effects of this program.
1)Four months after the end of the program, 64% of the participants had started to conduct clinical research.
2)This program may increase the number of research colleagues that can discuss clinical research.
3)This program could enhance the confidence(self–efficacy)of health care professionals in clinical research.


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