{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:41:55Z","timestamp":1792798915542,"version":"4.5.0"},"reference-count":23,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"unspecified","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Eisai Inc., Nutley, NJ, USA","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,1,20]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In Study 309\/KEYNOTE-775 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03517449\">NCT03517449<\/jats:ext-link>\n                      ), lenvatinib+pembrolizumab versus chemotherapy significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in advanced endometrial cancer (EC). We report 5-year follow-up results.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants had advanced\/recurrent\/metastatic EC with progressive disease after one prior platinum-based chemotherapy regimen, measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and no prior receipt of anti-programmed cell death protein 1 or anti-programmed cell death ligand 1 agents. Participants were randomized 1:1 to lenvatinib 20\u2009mg orally once daily plus pembrolizumab 200\u2009mg intravenously every 3 weeks or chemotherapy (doxorubicin or paclitaxel). Pembrolizumab was given for \u226435 cycles. Primary endpoints were OS and PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included ORR per RECIST v1.1 by BICR and safety. Efficacy endpoints were analyzed using Cox regression, Kaplan-Meier, and Miettinen and Nurminen methodology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>827 participants were randomized. At data cut-off (February 26, 2025), overall median follow-up was 68.8 months; 139 participants were alive (lenvatinib+pembrolizumab, n=86; chemotherapy, n=53), and all had ended their treatment in this study. Five-year OS rate was 16.7% with lenvatinib+pembrolizumab versus 7.3% with chemotherapy in mismatch repair-proficient EC, 36.5% versus 9.8% in mismatch repair-deficient EC, and 19.9% versus 7.7% in all-comers. Five-year PFS rates were 6.3% versus 2.1%, 26.4% versus 10.8%, and 9.8% versus 3.2%, respectively. In all-comers, treatment-related adverse events led to any treatment discontinuation in 32.3% versus 5.9%. Subsequent systemic anticancer therapy was used by 44.8% versus 51.2% (lenvatinib+pembrolizumab by 2.4% vs 10.1%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Results were consistent with the primary analysis despite increased use of subsequent systemic anticancer therapy and crossover to lenvatinib+pembrolizumab in the chemotherapy group. The continued durable benefit, including OS, with lenvatinib+pembrolizumab\u2009and no new safety signals lend further support for this regimen as a standard of care therapy for EC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013713","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T13:35:21Z","timestamp":1771508121000},"page":"e013713","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309\/KEYNOTE-775"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03517449","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03517449","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9793-7614","authenticated-orcid":false,"given":"Vicky","family":"Makker","sequence":"first","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Colombo","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Program, European Institute of Oncology, IRCSS, Milan, Italy"},{"name":"Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy"},{"name":"Mario Negri Gynecologic Oncology (MaNGO), Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Casado","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Clinico Universitario San Carlos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro D","family":"Santin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeline","family":"Colomba","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8215-5887","authenticated-orcid":false,"given":"David S","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Pignata","sequence":"additional","affiliation":[{"name":"Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy"},{"name":"Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO), Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Yonemori","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center Hospital, Chuo-ku, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Man","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Baron-Hay","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Ray-Coquard","sequence":"additional","affiliation":[{"name":"Medical Oncology 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