{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:34:54Z","timestamp":1789598094282,"version":"build-2803163510"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In MONARCH 2, abemaciclib plus fulvestrant significantly improved median progression-free survival (PFS, 16.4 vs 9.3\u00a0months, hazard ratio [HR] 0.553) and overall survival (OS, 46.7 vs 37.3\u00a0months; HR 0.757) compared with placebo plus fulvestrant in hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer (ABC) patients who were endocrine therapy (ET) resistant, regardless of menopausal status. Here, we report findings in the premenopausal subgroup of the MONARCH 2 trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The premenopausal subgroup included patients with natural menstrual bleeding who received a gonadotropin-releasing hormone agonist at least 4\u00a0weeks prior to study treatment start date and for the entire study duration. Of the 669 patients enrolled in the MONARCH 2 trial, 114 were premenopausal (abemaciclib plus fulvestrant,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200972; placebo plus fulvestrant,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200942), and were included in this analysis. The primary objective was investigator-assessed PFS and secondary objectives were OS, objective response rate, and safety and tolerability. Exploratory analyses included time to second disease progression (PFS2), time to chemotherapy (TTC), and chemotherapy-free survival (CFS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At the primary objective cutoff (February 14, 2017), median PFS was not reached for the abemaciclib plus fulvestrant arm versus 10.52\u00a0months for the placebo plus fulvestrant arm (HR 0.415; 95% CI 0.246\u20130.698). At the pre-specified OS interim cutoff (20-June-2019), median PFS was 28.6\u00a0months in the abemaciclib plus fulvestrant arm compared with 10.26\u00a0months in the placebo plus fulvestrant arm (HR 0.477; 95% CI 0.302\u20130.755). A numerical OS benefit was observed with abemaciclib plus fulvestrant compared to fulvestrant alone (HR 0.689; 95% CI 0.379\u20131.252, median, not reached vs 47.3\u00a0months). Improvements were also observed for the exploratory outcomes of PFS2 (HR 0.599), TTC (HR 0.674), and CFS (HR 0.642) with the addition of abemaciclib to fulvestrant. The safety profile was generally consistent with results disclosed previously.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Results of the premenopausal subgroup in the MONARCH 2 trial were consistent with the improved clinical outcomes observed in the intent-to-treat population. The analysis provides support for the use of abemaciclib plus fulvestrant (with ovarian suppression) as an effective treatment option for premenopausal patients with HR+, HER2- ABC who are ET-resistant.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Clinical trial registration<\/jats:italic>\n                      : NCT02107703. Registered April 08, 2014- Retrospectively registered,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02107703\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02107703<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13058-021-01463-2","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T07:03:14Z","timestamp":1629702194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial"],"prefix":"10.1186","volume":"23","author":[{"given":"Patrick","family":"Neven","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope S.","family":"Rugo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Tolaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroji","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Toi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Goetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Kaufman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Haddad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla C.","family":"Hurt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"George W.","family":"Sledge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"1463_CR1","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1001\/jama.2013.776","volume":"309","author":"RH Johnson","year":"2013","unstructured":"Johnson RH, Chien FL, Bleyer A. 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Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with hormone receptor positive\/human epidermal growth factor receptor 2 negative (HR+\/HER2\u2212) advanced breast cancer (ABC) treated with endocrine therapy (ET) \u00b1 ribociclib. 2020 San Antonio Breast Cancer Symposium, 2020. https:\/\/www.sabcs.org\/Portals\/SABCS2016\/2020%20SABCS\/ALL%20ABSTRACTS%202-9.pdf?ver=2020-12-09-104626-337"}],"container-title":["Breast Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13058-021-01463-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13058-021-01463-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13058-021-01463-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T07:11:51Z","timestamp":1629702711000},"score":1,"resource":{"primary":{"URL":"https:\/\/breast-cancer-research.biomedcentral.com\/articles\/10.1186\/s13058-021-01463-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1463"],"URL":"https:\/\/doi.org\/10.1186\/s13058-021-01463-2","relation":{},"ISSN":["1465-542X"],"issn-type":[{"value":"1465-542X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,23]]},"assertion":[{"value":"8 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with the International Council for Harmonization Good Clinical Practice Guidelines. All patients provided written informed consent. The final protocol, any amendments, and informed consent documentations were reviewed and approved by the Institutional Review Boards at each of the investigational centers participating in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"PN declares no conflicts of interest. HSR reports research grant to her institution from Eli Lilly and Company, Pfizer, Merck, Novartis, Genentech, OBI, Odonate, Daiichi-Sankyo, Eisai, Seattle Genetics, Macrogenics, Sermonixs, Immunomedics, AstraZeneca; travel support from Daiichi- Sankyo, Mylan, Pfizer, Merck, Novartis, AstraZeneca, Macrogenics; and honoraria from Puma, Mylan, and Samsung. SMT reports research grants to her institute and personal fees (honoraria for consulting\/advisory board) from Eli Lilly and Company, AstraZeneca, Merck, Nektar, Novartis, Pfizer, Genentech\/Roche, Exelixis, Bristol-Myers Squibb, Eisai, Nanostring, Sanofi, Odonate, Immunomedics\/Gilead; honoraria for advisory board\/consulting from Puma, Celldex, Seattle Genetics, Silverback Therapeutics, G1 Therapeutics, Abbvie, Athenex, OncoPep, Kyowa Kirin Pharmaceuticals, Daiichi-Sankyo, CytomX, Samsung Bioepsis Inc., Certara, Mersana Therapeutics, OncoSec; and research funding from Cyclacel. HI reports honoraria and consulting fees from Chugai, Novartis, AstraZeneca, Pfizer, Eli Lilly and Company, Daichi-Sankyo, Eisai, Kyowa Hakko Kirin; grants from MSD, Bayer, Nihon Kayaku, Boehringer Ingelheim, Sanofi; and personal fees from Taiho. MT reports research grant and honoraria from Chugai, Takeda, Pfizer, Kyowa-Kirin, Taiho, Eisai, AstraZeneca, Daiichi-Sankyo, Shimadzu, Yakult, and Nippon Kayaku; research grant from JBCRG association, Astellas, AFI technologies, Shionogi, and GL Science; advisory role at Kyowa-Kirin, Daiichi-Sankyo, Eli Lilly and Company, Konica Minolta, Athenex Oncology, Bertis, Terumo, Luxonus, and Kansai Medical Net; honoraria from BMS, Eli Lilly and Company, MSD, Exact Science, Novartis, and Konica Minolta. He is also on the Board of Directors for DBCRG association, Organization for Oncology and Translational Research, Kyoto Breast Cancer Research Network. MPG reports consulting fees to his institution from Eagle pharmaceuticals, Biovica, Novartis, Context Therapeutics, Biotheranostics, and AstraZeneca; research grants and consulting fees to his institution from Eli Lilly and Company, Pfizer, and Sermonix. PAK reports grants from Eli Lilly and Company. YL, NH, and KCH are employees of Eli Lilly and Company. GWS reports grants and nonfinancial support from Stanford University during the conduct of the study; personal fees from Radius Pharmaceuticals and Verseau Therapeutics, grants from Pfizer, personal fees from Symphogen, personal fees and nonfinancial support from Tessa, and personal fees from Syndax outside the submitted work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"87"}}