Clinicopathologic features and outcomes of patients with microsatellite instability-high endometrial cancer treated with pembrolizumab in Japan: the KCOG-G1902S/1903S study
Objective: To characterize clinicopathologic features of microsatellite instability-high (MSI-high) gynecologic malignancies in Japan and evaluate outcomes of pembrolizumab in MSI-high endometrial cancer, including an exploratory assessment of MLH1 promoter methylation and obesity.Methods: Gynecologic malignancies undergoing routine MSI testing at 11 institutions were registered (KCOG-G1902S).Clinicopathologic data of MSI-high cases were collected from medical records.Patients with MSI-high endometrial cancer treated with pembrolizumab were prospectively followed (KCOG-G1903S).MLH1 promoter methylation was assessed in tumors with MLH1 loss, and exploratory analyses evaluated outcomes according to MLH1 methylation status and body mass index (BMI).Results: Among 529 tumors tested, 56 (10.6%) were MSI-high, most arising in the endometrium (52/251; 20.7%).MSI-high tumors from other organs were predominantly endometrioid.All MSI-high tumors showed mismatch repair protein loss on immunohistochemistry; 41/56 (73.2%) demonstrated PMS2 and/or MLH1 loss.Pembrolizumab was administered to 25 patients with MSI-high endometrial cancer.The objective response rate was 48% (12/25), with median progression-free survival (PFS) of 21.2 months and overall survival
Authors
- Yasuyuki Hirashima (ORCID: https://orcid.org/0000-0003-0269-9313)
- Yoko Kashima (ORCID: https://orcid.org/0000-0003-0212-2047)
- Naoyuki Iwahashi (ORCID: https://orcid.org/0000-0002-6422-325X)
- Kaori Yoriki (ORCID: https://orcid.org/0000-0002-9893-6688)
- Atsushi Arakawa
- Kimihiko Ito (ORCID: https://orcid.org/0000-0002-3115-7997)
- Kentaro Kai (ORCID: https://orcid.org/0000-0003-2916-5303)
- Takahiro Katsuda (ORCID: https://orcid.org/0000-0002-5124-5599)
- A Mochizuki
- Noriomi Matsumura (ORCID: https://orcid.org/0000-0002-4512-7975)
- Tomoyuki Otani (ORCID: https://orcid.org/0000-0002-4351-324X)
- Kosuke Murakami (ORCID: https://orcid.org/0000-0003-4278-5849)
- Hidekatsu Nakai (ORCID: https://orcid.org/0000-0002-9994-2131)
- Takashi Motohashi (ORCID: https://orcid.org/0000-0003-3459-7485)
- Satoe Fujiwara (ORCID: https://orcid.org/0000-0003-4466-2068)
- Hiroaki Nagano (ORCID: https://orcid.org/0000-0001-8208-1876)
- Yoh Hayasaki (ORCID: https://orcid.org/0009-0007-2000-1181)
- Michiko Kubo‐Kaneda (ORCID: https://orcid.org/0000-0003-3493-8753)
- Emi Yoshioka (ORCID: https://orcid.org/0000-0003-3912-5006)
Institutions
- Kurume University (JP)
- Mie University (JP)
- Oita University (JP)
- Wakayama Medical University (JP)
- Nagoya City University (JP)
- Kyoto Prefectural University of Medicine (JP)
- Shizuoka Cancer Center (JP)
- National Sanyo Hospital (JP)
- Kansai Rosai Hospital (JP)
- Kindai University Sakai Hospital (JP)
- Tokyo Women's Medical University Adachi Medical Center (JP)
- Tokyo Women's Medical University (JP)
- Nagoya Medical Center (JP)
- Gifu University (JP)
- Osaka University of Pharmaceutical Sciences (JP)
Publication Details
- Journal
- Journal of Gynecologic Oncology
- Published
- 2026-09-01
- DOI
- https://doi.org/10.3802/jgo.2027.38.e19
- Primary Topic
- Endometrial and Cervical Cancer Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Society for the Promotion of Science