{"doi":"10.1200/jco.23.02036","title":"Randomized Phase III Study of Amcenestrant Plus Palbociclib Versus Letrozole Plus Palbociclib in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Primary Results From AMEERA-5","abstract":"<jats:sec><jats:title>PURPOSE</jats:title><jats:p> AMEERA-5 investigated amcenestrant (oral selective estrogen receptor [ER] degrader) plus palbociclib versus letrozole plus palbociclib as first-line treatment for ER-positive/human epidermal growth factor receptor 2–negative (ER+/HER2–) advanced/metastatic breast cancer (aBC). </jats:p></jats:sec><jats:sec><jats:title>MATERIALS AND METHODS</jats:title><jats:p> In AMEERA-5 (ClinicalTrials.gov identifier: NCT04478266 ), a double-blind, double-dummy, international phase III trial, adult pre-/post-menopausal women and men without previous systemic therapy for ER+/HER2– aBC were randomly assigned 1:1 to amcenestrant 200 mg once daily + standard palbociclib dosage (125 mg once daily, 21 days on/7 days off) or letrozole 2.5 mg once daily + standard palbociclib dosage, stratified by de novo metastatic disease, postmenopausal women, and visceral metastasis. The primary end point was progression-free survival (PFS), compared using a stratified log-rank test with one-sided type I error rate of 2.5%. Secondary end points included overall survival (key secondary), pharmacokinetics, and safety. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> Between October 14, 2020, and December 2, 2021, 1,068 patients were randomly assigned to amcenestrant + palbociclib (N = 534) or letrozole + palbociclib (N = 534). At the interim analysis (median follow-up 8.4 months), the stratified hazard ratio for PFS was 1.209 (95% CI, 0.939 to 1.557; one-sided P value = .9304); therefore, the study was stopped for futility. The 6-month PFS rate was 82.7% (95% CI, 79.0 to 85.8) with amcenestrant + palbociclib versus 86.9% (95% CI, 83.5 to 89.6) with letrozole + palbociclib. In the amcenestrant + palbociclib versus letrozole + palbociclib groups, treatment-emergent adverse events (any grade) occurred in 85.6% versus 85.4% of patients and grade ≥3 events in 46.3% versus 60.8%, respectively. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> The AMEERA-5 study was discontinued on the basis of the recommendation of the data monitoring committee at the interim futility analysis. No new safety signals were identified. </jats:p></jats:sec>","journal":"Journal of Clinical Oncology","year":2024,"id":601374,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"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":37110,"name":"Sara A. Hurvitz","orcid":"0000-0001-7808-7191","position":1,"is_corresponding":false},{"id":1541997,"name":"Joyce O'Shaughnessy","orcid":null,"position":2,"is_corresponding":false},{"id":550853,"name":"Suzette Delaloge","orcid":"0000-0003-2106-9165","position":3,"is_corresponding":false},{"id":231712,"name":"Hiroji Iwata","orcid":"0000-0002-0242-4718","position":4,"is_corresponding":false},{"id":34069,"name":"Hope S. Rugo","orcid":"0000-0001-6710-4814","position":5,"is_corresponding":false},{"id":537992,"name":"Patrick Neven","orcid":"0000-0002-1434-9460","position":6,"is_corresponding":false},{"id":1541999,"name":"Dheepak Kanagavel","orcid":"0000-0002-7684-8580","position":7,"is_corresponding":false},{"id":862825,"name":"Patrick Cohen","orcid":"0009-0008-1187-1123","position":8,"is_corresponding":false},{"id":862826,"name":"Gautier Paux","orcid":"0000-0003-3002-6351","position":9,"is_corresponding":false},{"id":1542000,"name":"Sylvaine Cartot-Cotton","orcid":null,"position":10,"is_corresponding":false},{"id":1542002,"name":"Maya Stefanova-Urena","orcid":null,"position":11,"is_corresponding":false},{"id":1542003,"name":"Laure Deyme","orcid":"0000-0002-5986-4765","position":12,"is_corresponding":false},{"id":1542006,"name":"Jihane Aouni","orcid":"0000-0003-0750-9881","position":13,"is_corresponding":false},{"id":1542008,"name":"Bernard Sebastien","orcid":null,"position":14,"is_corresponding":false},{"id":105199,"name":"Aditya Bardia","orcid":"0000-0003-4885-1157","position":15,"is_corresponding":false},{"id":303791,"name":"Javier Cortés","orcid":"0000-0001-7623-1583","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Randomized Phase III Study of Amcenestrant Plus Palbociclib Versus Letrozole Plus Palbociclib in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Primary Results From AMEERA-5","abstract":"<jats:sec><jats:title>PURPOSE</jats:title><jats:p> AMEERA-5 investigated amcenestrant (oral selective estrogen receptor [ER] degrader) plus palbociclib versus letrozole plus palbociclib as first-line treatment for ER-positive/human epidermal growth factor receptor 2–negative (ER+/HER2–) advanced/metastatic breast cancer (aBC). </jats:p></jats:sec><jats:sec><jats:title>MATERIALS AND METHODS</jats:title><jats:p> In AMEERA-5 (ClinicalTrials.gov identifier: NCT04478266 ), a double-blind, double-dummy, international phase III trial, adult pre-/post-menopausal women and men without previous systemic therapy for ER+/HER2– aBC were randomly assigned 1:1 to amcenestrant 200 mg once daily + standard palbociclib dosage (125 mg once daily, 21 days on/7 days off) or letrozole 2.5 mg once daily + standard palbociclib dosage, stratified by de novo metastatic disease, postmenopausal women, and visceral metastasis. The primary end point was progression-free survival (PFS), compared using a stratified log-rank test with one-sided type I error rate of 2.5%. Secondary end points included overall survival (key secondary), pharmacokinetics, and safety. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> Between October 14, 2020, and December 2, 2021, 1,068 patients were randomly assigned to amcenestrant + palbociclib (N = 534) or letrozole + palbociclib (N = 534). At the interim analysis (median follow-up 8.4 months), the stratified hazard ratio for PFS was 1.209 (95% CI, 0.939 to 1.557; one-sided P value = .9304); therefore, the study was stopped for futility. The 6-month PFS rate was 82.7% (95% CI, 79.0 to 85.8) with amcenestrant + palbociclib versus 86.9% (95% CI, 83.5 to 89.6) with letrozole + palbociclib. In the amcenestrant + palbociclib versus letrozole + palbociclib groups, treatment-emergent adverse events (any grade) occurred in 85.6% versus 85.4% of patients and grade ≥3 events in 46.3% versus 60.8%, respectively. </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> The AMEERA-5 study was discontinued on the basis of the recommendation of the data monitoring committee at the interim futility analysis. No new safety signals were identified. </jats:p></jats:sec>","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38889373","pmcid":null,"openalex_id":"https://openalex.org/W4399765251","authors":[],"funders":[],"total_grants":0,"fwci":4.5681,"citation_percentile":0.95630209,"influential_citations":0,"citation_trend":[{"year":2024,"count":2},{"year":2025,"count":10},{"year":2026,"count":4}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO.23.02036","host_type":"publisher"},{"url":"https://doi.org/10.1200/jco.23.02036","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38889373","host_type":"repository"}],"fields_of_study":["Advanced Breast Cancer Therapies","HER2/EGFR in Cancer Research","Estrogen and related hormone effects","Humans","Female","Letrozole","Breast Neoplasms","Middle Aged","Pyridines","Antineoplastic Combined Chemotherapy Protocols","Erb-b2 Receptor Tyrosine Kinases","Receptors, Estrogen","Aged","Piperazines","Double-Blind Method","Adult","Male","Breast Neoplasms, Male","Aged, 80 and over"],"mesh_terms":["Letrozole","Adult","Aged","Aged, 80 and over","Antineoplastic Combined Chemotherapy Protocols","Breast Neoplasms","Double-Blind Method","Female","Humans","Male","Middle Aged","Piperazines","Pyridines","Receptors, Estrogen","Breast Neoplasms, Male","Erb-b2 Receptor Tyrosine Kinases","Receptor, ErbB-2"],"keywords":["Palbociclib","Letrozole","Medicine","Metastatic breast cancer","Clinical endpoint","Internal medicine","Oncology","Breast cancer","Estrogen receptor","Gynecology","Cancer","Urology","Randomized controlled trial","Tamoxifen"],"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":"2026-07-29T16:07:03.478030Z","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":[]}