{"doi":"10.1136/jitc-2025-013713","title":"Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309/KEYNOTE-775","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 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy (doxorubicin or paclitaxel). Pembrolizumab was given for ≤35 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 and no new safety signals lend further support for this regimen as a standard of care therapy for EC.</jats:p>\n                  </jats:sec>","journal":"Journal for ImmunoTherapy of Cancer","year":2026,"id":642266,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":50716,"name":"Nicoletta Colombo","orcid":"0000-0003-2225-715X","position":1,"is_corresponding":false},{"id":691181,"name":"Antonio Casado","orcid":"0000-0002-8200-3306","position":2,"is_corresponding":false},{"id":1670397,"name":"Alessandro D Santin","orcid":null,"position":3,"is_corresponding":false},{"id":1670399,"name":"Emeline Colomba","orcid":null,"position":4,"is_corresponding":false},{"id":66131,"name":"David S. Miller","orcid":"0000-0002-8215-5887","position":5,"is_corresponding":false},{"id":346845,"name":"Keiichi Fujiwara","orcid":"0000-0002-7388-0243","position":6,"is_corresponding":false},{"id":258141,"name":"Sandro Pignata","orcid":"0000-0002-8836-2633","position":7,"is_corresponding":false},{"id":916396,"name":"Kan Yonemori","orcid":"0000-0002-7624-7611","position":8,"is_corresponding":false},{"id":1070604,"name":"Yong Man Kim","orcid":"0000-0002-4222-3400","position":9,"is_corresponding":false},{"id":1670404,"name":"Sally Baron-Hay","orcid":null,"position":10,"is_corresponding":false},{"id":50152,"name":"Isabelle Ray-Coquard","orcid":null,"position":11,"is_corresponding":false},{"id":1670407,"name":"Ronnie Shapira-Frommer","orcid":null,"position":12,"is_corresponding":false},{"id":826561,"name":"Rebecca Kristeleit","orcid":"0000-0003-3825-1326","position":13,"is_corresponding":false},{"id":1046134,"name":"Shin Nishio","orcid":"0000-0003-2526-630X","position":14,"is_corresponding":false},{"id":1670408,"name":"Shiro Suzuki","orcid":null,"position":15,"is_corresponding":false},{"id":1670409,"name":"Eva M Guerra Alía","orcid":null,"position":16,"is_corresponding":false},{"id":1670410,"name":"Ulus A Sanli","orcid":null,"position":17,"is_corresponding":false},{"id":1670411,"name":"Frederic Selle","orcid":null,"position":18,"is_corresponding":false},{"id":1670412,"name":"Ayumi Shikama","orcid":null,"position":19,"is_corresponding":false},{"id":1670413,"name":"Jorge L Martínez Rodríguez","orcid":null,"position":20,"is_corresponding":false},{"id":1670414,"name":"Zafer Arik","orcid":null,"position":21,"is_corresponding":false},{"id":1670415,"name":"Ali Arican","orcid":null,"position":22,"is_corresponding":false},{"id":1670416,"name":"Alexandra Sebastianelli","orcid":null,"position":23,"is_corresponding":false},{"id":502902,"name":"Zhou Yu","orcid":"0000-0003-3213-4583","position":24,"is_corresponding":false},{"id":1670417,"name":"Jodi McKenzie","orcid":null,"position":25,"is_corresponding":false},{"id":1670418,"name":"Stephan Kruger","orcid":null,"position":26,"is_corresponding":false},{"id":1670419,"name":"Robin Meng","orcid":null,"position":27,"is_corresponding":false},{"id":1670420,"name":"Chinyere E Okpara","orcid":null,"position":28,"is_corresponding":false},{"id":406831,"name":"Domenica Lorusso","orcid":"0000-0003-0981-0598","position":29,"is_corresponding":false},{"id":235765,"name":"Vicky Makker","orcid":"0000-0001-9793-7614","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309/KEYNOTE-775","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 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy (doxorubicin or paclitaxel). Pembrolizumab was given for ≤35 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 and no new safety signals lend further support for this regimen as a standard of care therapy for EC.</jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41714113","pmcid":"PMC12927346","openalex_id":"https://openalex.org/W7130510683","authors":[],"funders":[{"funder_name":"Eisai Inc., Nutley, NJ, USA","grant_id":"NA","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA008748","title":null}],"total_grants":2,"fwci":11.4051,"citation_percentile":0.95790028,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://jitc.bmj.com/content/14/2/e013713.full.pdf","host_type":"journal"},{"url":"https://jitc.bmj.com/content/14/2/e013713.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1136/jitc-2025-013713","host_type":"publisher"},{"url":"https://doi.org/10.1136/jitc-2025-013713","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41714113","host_type":"repository"},{"url":"https://kclpure.kcl.ac.uk/portal/en/publications/36acc004-5111-4bdf-82ec-ea1c36161769","host_type":"repository"},{"url":"https://univ-lyon1.hal.science/hal-05538264","host_type":"repository"},{"url":"https://doaj.org/article/050c1254711542c5ad86e0720dbee803","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12927346/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12927346","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12927346?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Endometrial and Cervical Cancer Treatments","Cancer Immunotherapy and Biomarkers","Ferroptosis and cancer prognosis"],"mesh_terms":["Adult","Aged","Antineoplastic Combined Chemotherapy Protocols","Female","Humans","Middle Aged","Phenylurea Compounds","Quinolines","Endometrial Neoplasms","Treatment Outcome","Antibodies, Monoclonal, Humanized"],"keywords":["Pembrolizumab","Lenvatinib","Regimen","Chemotherapy","Phases of clinical research","Standard of care"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T22:09:25.138821Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}