{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T11:32:19Z","timestamp":1782732739543,"version":"3.54.5"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The Proactive Molecular Risk Classifier for Endometrial Cancer has identified four risk groups for the prognosis of endometrial cancer. Lenvatinib plus pembrolizumab was recently approved as a second-line treatment for unresectable endometrial cancer, but reports in clinical practice are lacking. The relationship between the efficacy of lenvatinib\/pembrolizumab and Proactive Molecular Risk Classifier for Endometrial Cancer classification is unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This single-centre retrospective study included patients who underwent lenvatinib\/pembrolizumab therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient, p53 abnormal and no specific molecular profile subtypes using immunohistochemistry. The response rate, progression-free survival and adverse events were evaluated using electronic medical records. The study was approved by the hospital\u2019s ethics committee (approval number: MH2022-093).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>This study enrolled 20 patients, who underwent a median follow-up of 17.8\u00a0months (95% confidence interval: 16.6\u201318.9). The best overall response rate was 60.0% (36.1\u201380.9), and the median progression-free survival was 11.6\u00a0months (2.9\u201320.3). The median progression-free survival in the p53 abnormal group (n =\u00a09) was 3.4\u00a0months (3.0\u20133.8); however, progression-free survival did not reach the median (P\u00a0&amp;lt;\u00a00.001) in the mismatch repair-deficient\/no specific molecular profile group (n\u00a0=\u00a011). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4\/20 (25.0%) patients, and partial responses were observed in all cases. No treatment-related deaths occurred.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The p53abn group in the Proactive Molecular Risk Classifier for Endometrial Cancer classification has a poor prognosis even after treatment with lenvatinib\/pembrolizumab.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jjco\/hyad192","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T11:42:47Z","timestamp":1705923767000},"page":"424-433","source":"Crossref","is-referenced-by-count":5,"title":["A single-institution retrospective exploratory analysis on the effectiveness and safety of lenvatinib plus pembrolizumab for advanced endometrial cancer: insights from ProMisE molecular classification system"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0589-2285","authenticated-orcid":false,"given":"Yohei","family":"Chiba","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Kagabu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsumasa","family":"Osakabe","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostic Pathology , School of Medicine, , Iwate , Japan"},{"name":"Iwate Medical University , School of Medicine, , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikako","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"},{"name":"Department of Obstetrics and Gynecology, Iwate Prefectural Ofunato Hospital , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sho","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Takatori","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Kaido","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadahiro","family":"Shoji","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Yanagawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostic Pathology , School of Medicine, , Iwate , Japan"},{"name":"Iwate Medical University , School of Medicine, , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsukasa","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine , Iwate , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,20]]},"reference":[{"key":"2024040806012135000_ref1"},{"issue":"5","key":"2024040806012135000_ref2","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1111\/jog.14724","article-title":"Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: annual patient report for 2017 and annual treatment report for 2012","volume":"47","author":"Nagase","year":"2021","journal-title":"J Obstet Gynaecol Res"},{"issue":"8","key":"2024040806012135000_ref3","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1097\/IGC.0000000000001346","article-title":"The clinical features of recurrent endometrial cancer in Japan: chemotherapy instead of radiotherapy as postoperative adjuvant treatment","volume":"28","author":"Iwase","year":"2018","journal-title":"Int J Gynecol Cancer"},{"issue":"19","key":"2024040806012135000_ref4","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1200\/JCO.2004.02.088","article-title":"Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a gynecologic oncology group study","volume":"22","author":"Thigpen","year":"2004","journal-title":"J Clin Oncol"},{"issue":"33","key":"2024040806012135000_ref5","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1200\/JCO.20.01076","article-title":"Carboplatin and paclitaxel for advanced endometrial cancer: final overall survival and adverse event analysis of a phase III trial (NRG oncology\/GOG0209)","volume":"38","author":"Miller","year":"2020","journal-title":"J Clin Oncol"},{"issue":"3","key":"2024040806012135000_ref6","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ygyno.2019.12.039","article-title":"Second-line lenvatinib in patients with recurrent endometrial cancer","volume":"156","author":"Vergote","year":"2020","journal-title":"Gynecol Oncol"},{"key":"2024040806012135000_ref7","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1200\/JCO.21.01874","article-title":"Pembrolizumab in patients with microsatellite instability-high advanced endometrial cancer: results from the KEYNOTE-158 study","volume":"40","author":"O'Malley","year":"2022","journal-title":"J Clin Oncol"},{"key":"2024040806012135000_ref8","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1056\/NEJMoa2108330","article-title":"Lenvatinib plus Pembrolizumab for advanced endometrial cancer","volume":"386","author":"Makker","year":"2022","journal-title":"New England J Med"},{"issue":"9","key":"2024040806012135000_ref9","doi-asserted-by":"crossref","first-page":"e1599","DOI":"10.1002\/onco.13883","article-title":"Characterization and management of adverse reactions in patients with advanced endometrial carcinoma treated with lenvatinib plus pembrolizumab","volume":"26","author":"Makker","year":"2021","journal-title":"Oncologist"},{"key":"2024040806012135000_ref10","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1111\/cas.15436","article-title":"Lenvatinib plus pembrolizumab in Japanese patients with endometrial cancer: results from study 309\/KEYNOTE-775","volume":"113","author":"Yonemori","year":"2022","journal-title":"Cancer Sci"},{"issue":"7447","key":"2024040806012135000_ref11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated genomic characterization of endometrial carcinoma","volume":"497","author":"Kandoth","year":"2013","journal-title":"Nature"},{"issue":"1","key":"2024040806012135000_ref12","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ygyno.2016.12.015","article-title":"Molecular approaches for classifying endometrial carcinoma","volume":"145","author":"Piulats","year":"2017","journal-title":"Gynecol Oncol"},{"issue":"9","key":"2024040806012135000_ref13","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1001\/jamaoncol.2015.2151","article-title":"Association of polymerase e-mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1","volume":"1","author":"Howitt","year":"2015","journal-title":"JAMA Oncol"},{"issue":"5","key":"2024040806012135000_ref14","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/cncr.30496","article-title":"Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer","volume":"123","author":"Talhouk","year":"2017","journal-title":"Cancer"},{"issue":"5","key":"2024040806012135000_ref15","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1093\/annonc\/mdy058","article-title":"Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series","volume":"29","author":"Kommoss","year":"2018","journal-title":"Ann Oncol"},{"issue":"29","key":"2024040806012135000_ref16","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1200\/JCO.20.00549","article-title":"Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy","volume":"38","author":"Le\u00f3n-Castillo","year":"2020","journal-title":"J Clin Oncol"},{"issue":"4","key":"2024040806012135000_ref17","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1136\/ijgc-2020-001822","article-title":"Adjuvant therapy for endometrial cancer in the era of molecular classification: radiotherapy, chemoradiation and novel targets for therapy","volume":"31","author":"Heerik","year":"2021","journal-title":"Int J Gynecol Cancer"},{"issue":"11","key":"2024040806012135000_ref18","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11111769","article-title":"Response to lenvatinib is associated with optimal relative dose intensity in hepatocellular carcinoma: experience in clinical settings","volume":"11","author":"Sasaki","year":"2019","journal-title":"Cancers (Basel)"},{"issue":"4","key":"2024040806012135000_ref19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0231828","article-title":"Relative dose intensity over the first four weeks of lenvatinib therapy is a factor of favorable response and overall survival in patients with unresectable hepatocellular carcinoma","volume":"15","author":"Kirino","year":"2020","journal-title":"PloS One"},{"issue":"2","key":"2024040806012135000_ref20","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"issue":"2","key":"2024040806012135000_ref21","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/ijgo.14923","article-title":"FIGO staging of endometrial cancer: 2023","volume":"162","author":"Berek","year":"2023","journal-title":"Int J Gynaecol Obstet"},{"key":"2024040806012135000_ref22","year":"2022"},{"issue":"2","key":"2024040806012135000_ref23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/his.13338","article-title":"Blinded histopathological characterisation of POLE exonuclease domain-mutant endometrial cancers: sheep in wolf's clothing","volume":"72","author":"Van Gool","year":"2018","journal-title":"Histopathology"},{"issue":"2","key":"2024040806012135000_ref24","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.3802\/jgo.2022.33.e15","article-title":"Clinical evaluation of a droplet digital PCR assay for detecting POLE mutations and molecular classification of endometrial cancer","volume":"33","author":"Kim","year":"2022","journal-title":"J Gynecol Oncol"},{"issue":"6","key":"2024040806012135000_ref25","doi-asserted-by":"crossref","first-page":"471","DOI":"10.4132\/jptm.2020.07.23","article-title":"The frequency of POLE-mutation in endometrial carcinoma and prognostic implications: a systemic review and meta-analysis","volume":"54","author":"Jumaah","year":"2020","journal-title":"J Pathol Transl Med"},{"issue":"1","key":"2024040806012135000_ref26","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ygyno.2014.05.006","article-title":"POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium","volume":"134","author":"Meng","year":"2014","journal-title":"Gynecol Oncol"},{"key":"2024040806012135000_ref27","article-title":"Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma","volume":"37","author":"Hunt","year":"2021","journal-title":"Gynecol Oncol Rep"},{"issue":"4","key":"2024040806012135000_ref28","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1007\/s12253-020-00829-9","article-title":"TCGA classification of endometrial cancer: the place of carcinosarcoma","volume":"26","author":"Travaglino","year":"2020","journal-title":"Pathol Oncol Res"},{"issue":"1","key":"2024040806012135000_ref29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/ijgo.13937","article-title":"Prognostic value of the TCGA molecular classification in uterine carcinosarcoma","volume":"158","author":"Travaglino","year":"2022","journal-title":"Int J Gynaecol Obstet"},{"issue":"7","key":"2024040806012135000_ref30","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41379-019-0220-1","article-title":"Impact of TP53 immunohistochemistry on the histological grading system for endometrial endometrioid carcinoma","volume":"32","author":"Yano","year":"2019","journal-title":"Mod Pathol"},{"issue":"1","key":"2024040806012135000_ref31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1136\/ijgc-2021-003017","article-title":"Phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer: ENGOT-en9\/LEAP-001","volume":"32","author":"Marth","year":"2022","journal-title":"Int J Gynecol Cancer"},{"issue":"1","key":"2024040806012135000_ref32","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41379-019-0358-x","article-title":"HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy","volume":"33","author":"Rottmann","year":"2020","journal-title":"Mod Pathol"},{"issue":"6","key":"2024040806012135000_ref33","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1007\/s00428-021-03017-5","article-title":"Histopathological features of HER2 overexpression in uterine carcinosarcoma: proposal for requirements in HER2 testing for targeted therapy","volume":"478","author":"Yoshida","year":"2021","journal-title":"Virchows Arch"},{"key":"2024040806012135000_ref34","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1200\/JCO.22.02558","article-title":"Trastuzumab Deruxtecan for human epidermal growth factor receptor 2-expressing advanced or recurrent uterine carcinosarcoma (NCCH1615): the STATICE trial","volume":"41","author":"Nishikawa","year":"2023","journal-title":"J Clin Oncol"},{"issue":"1","key":"2024040806012135000_ref35","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ygyno.2018.03.058","article-title":"Assessment and management of diarrhea following VEGF receptor TKI treatment in patients with ovarian cancer","volume":"150","author":"Liu","year":"2018","journal-title":"Gynecol Oncol"},{"issue":"3","key":"2024040806012135000_ref36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.cllc.2018.10.002","article-title":"Association between immune-related adverse events and efficacy of immune checkpoint inhibitors in non-small-cell lung cancer","volume":"20","author":"Grangeon","year":"2019","journal-title":"Clin Lung Cancer"},{"issue":"12","key":"2024040806012135000_ref37","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1001\/jamaoncol.2020.5012","article-title":"Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer","volume":"6","author":"Shankar","year":"2020","journal-title":"JAMA Oncol"},{"issue":"7","key":"2024040806012135000_ref38","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1007\/s00262-021-03115-y","article-title":"The prognostic impact of mild and severe immune-related adverse events in non-small cell lung cancer treated with immune checkpoint inhibitors: a multicenter retrospective study","volume":"71","author":"Wang","year":"2022","journal-title":"Cancer Immunol Immunother"},{"issue":"10","key":"2024040806012135000_ref39","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13102365","article-title":"Investigating the impact of immune-related adverse events, glucocorticoid use and immunotherapy interruption on long-term survival outcomes","volume":"13","author":"Bruy\u00e8re","year":"2021","journal-title":"Cancers (Basel)"}],"container-title":["Japanese Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/54\/4\/424\/57174386\/hyad192.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jjco\/article-pdf\/54\/4\/424\/57174386\/hyad192.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T06:02:07Z","timestamp":1712556127000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jjco\/article\/54\/4\/424\/7584460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,20]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,1,20]]},"published-print":{"date-parts":[[2024,4,6]]}},"URL":"https:\/\/doi.org\/10.1093\/jjco\/hyad192","relation":{},"ISSN":["1465-3621"],"issn-type":[{"value":"1465-3621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,4]]},"published":{"date-parts":[[2024,1,20]]}}}