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For all-comers, there was no difference in PFS (HR 0.78, 95% CI 0.4-1.4,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.38), OS (HR 0.8, 95% CI 0.4-1.5,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.46), ORR (44.1% vs 25.7%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.11), or toxicity-related treatment discontinuation (4 [8.6%] vs 3 [11.4%],\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.22). Among those with prior endocrine therapy, ORR was higher in the experimental arm (61.5% vs 0.0%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Within the experimental arm,\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    <jats:sub>mut<\/jats:sub>\n                    tumors were associated with improved PFS (HR 0.27, 95% CI 0.1-0.7,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006) and OS (HR 0.24, 95% CI 0.1-0.7,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004) compared to those with non-\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    <jats:sub>mut<\/jats:sub>\n                    tumors. Despite no survival improvement in all-comers, addition of ribociclib to everolimus\/letrozole may improve efficacy in patients with prior endocrine therapy and cases with\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    <jats:sub>mut<\/jats:sub>\n                    tumors may have prolonged response.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-77049-3","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:03:40Z","timestamp":1788282220000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of everolimus and letrozole with or without ribociclib in recurrent endometrial cancer: a phase 2 randomized clinical trial"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1446-9574","authenticated-orcid":false,"given":"Jeffrey A.","family":"How","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1922-0156","authenticated-orcid":false,"given":"Shannon N.","family":"Westin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barrett","family":"Lawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Tandon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7255-2360","authenticated-orcid":false,"given":"Rugang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4335-4151","authenticated-orcid":false,"given":"Amir A.","family":"Jazaeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4242-1762","authenticated-orcid":false,"given":"Anil K.","family":"Sood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Onstad Grinsfelder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Schmeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Vining","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M.","family":"Fix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8023-4665","authenticated-orcid":false,"given":"Yibo","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikayla B.","family":"Bowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen H.","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda S.","family":"Yates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Broaddus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8784-9212","authenticated-orcid":false,"given":"Pamela T.","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"77049_CR1","doi-asserted-by":"publisher","unstructured":"Bray, F. et al. 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S.N.W. reports grants\/contracts to institution (AstraZeneca, AvengeBio, Bayer, Bio-Path, Clovis Oncology\/Pharm&, Daiichi Sankyo, GSK, Jazz Pharmaceuticals, Loxo, Mereo, Novartis, Nuvectis, Pfizer, Roche\/Genentech, Verastem, Zentalis) and consulting (AbbVie, AstraZeneca, Bayer, Caris, Clovis Oncology\/Pharma&, Corcept, Daiichi Sankyo, Eisai, Genmab, Gilead, GSK, Immunocore, ImmunoGen, Incyte, Lilly, Loxo, Merck, Mereo, NGM Bio, Nuvectis, Pfizer, Roche\/Genentech, SeaGen, Verastem, Zentalis, ZielBio). A.A.J. reports personal fees (Gerson Lehrman Group, Guidepoint, Iovance advisory board meeting, NuProbe, Simcere, PACT Pharma, Genentech-Roche, Eisai, Agenus, and Macrogenics), grants (AstraZeneca, Bristol Myers Squibb, Iovance, Aravive, Pfizer, Immatics US, Eli Lilly, Merck), and stock\/stock options (AvengeBio). P.T.S. reports clinical trial support\/grants to the institution (Merck, Novartis, Incyte, GSK) and consulting fees (Aadi, GSK, and Eisai). All other authors report no conflicts of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"10413"}}