{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:07:47Z","timestamp":1790075267316,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The treatment-free interval (TFI) predicts benefit from platinum rechallenge in gynecological cancers, but its prognostic value in patients receiving second-line pembrolizumab plus lenvatinib for recurrent endometrial cancer (EC) is unknown. We evaluated whether the TFI is associated with survival and toxicity in this setting. Methods: Using the TriNetX Research Network (122 healthcare organizations, United States and Europe), we identified adults aged 18\u201390 years with advanced or recurrent EC between January 2018 and June 2026 who received three to six cycles of first-line carboplatin plus paclitaxel, progressed, and then received pembrolizumab plus lenvatinib. Patients were stratified by TFI (&lt;6 months, Cohort 1; \u22656 months, Cohort 2) and matched 1:1 by propensity score. The primary outcome was overall survival (OS), compared using Kaplan\u2013Meier and Cox proportional-hazards methods; adverse-event risks were exploratory outcomes compared using z-tests for the risk difference, without adjustment for multiple comparisons. Results: Of 420 eligible patients, 119 remained in each cohort after matching, with balanced baseline characteristics. Median OS was 10.0 months in Cohort 1 versus 23.6 months in Cohort 2 (hazard ratio 1.60, 95% confidence interval 1.12\u20132.29; p = 0.009), and 3-year OS was 32.5% versus 40.5%. Grade 3 anemia occurred earlier and more often in Cohort 1 (hazard ratio 1.74, 95% confidence interval 1.10\u20132.76; p = 0.017), whereas hypothyroidism was less frequent (31.9% versus 47.1%; p = 0.017); the remaining adverse events did not differ significantly between cohorts. Conclusions: A TFI \u2265 6 months is associated with significantly longer OS and a largely similar toxicity profile. The TFI is a readily available, real-world evidence-based reference for the prognosis and for the comparative adverse-event profile of the two TFI groups in this setting.<\/jats:p>","DOI":"10.3390\/cancers18193076","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:21:48Z","timestamp":1790072508000},"page":"3076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Treatment-Free Interval as a Prognostic Factor for Survival Outcomes in Patients with Advanced or Recurrent Endometrial Cancer Treated with Pembrolizumab Plus Lenvatinib: A Multi-Institutional Real-World Cohort Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Chih-Wen","family":"Su","sequence":"first","affiliation":[{"name":"Doctoral Program in Translational Medicine, Rong Hsing Translational Medicine Research Center, National Chung Hsing University, Taichung 402202, Taiwan"},{"name":"Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7654-2699","authenticated-orcid":false,"given":"Shao-Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Yu-Hsiang","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"College of Health Care and Management, Chung Shan Medical University, Taichung 402367, Taiwan"},{"name":"Palliative Care Unit, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Ting-Fang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Yen-Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Chun-Ting","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Shih-Tien","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"Center for General Education, Ling Tung University, Taichung 408284, Taiwan"},{"name":"School of Medicine, China Medical University, Taichung 406040, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Chih-Ku","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"Department of Animal Science and Biotechnology, Tunghai University, Taichung 407224, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5561-7110","authenticated-orcid":false,"given":"Lou","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"Department of Food and Nutrition, Providence University, Taichung 433303, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Sheau-Feng","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"Palliative Care Unit, Taichung Veterans General Hospital, Taichung 407219, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-4320","authenticated-orcid":false,"given":"Chien-Hsing","family":"Lu","sequence":"additional","affiliation":[{"name":"Doctoral Program in Translational Medicine, Rong Hsing Translational Medicine Research Center, National Chung Hsing University, Taichung 402202, Taiwan"},{"name":"Department of Gynecology and Obstetrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan"},{"name":"Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3509-3713","authenticated-orcid":false,"given":"Chia-Che","family":"Chang","sequence":"additional","affiliation":[{"name":"Doctoral Program in Translational Medicine, Rong Hsing Translational Medicine Research Center, National Chung Hsing University, Taichung 402202, Taiwan"},{"name":"Department of Life Sciences, National Chung Hsing University, Taichung 402202, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, Rong Hsing Translational Medicine Research Center,  National Chung Hsing University, Taichung 402202, Taiwan"},{"name":"The iEGG and Animal Biotechnology Research Center, National Chung Hsing University, Taichung 402202, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413305, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, Taichung 406040, Taiwan"},{"name":"Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 110301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA 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