Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial

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dc.authorscopusid35420152000
dc.authorscopusid57216427862
dc.authorscopusid7006065486
dc.authorscopusid15119719300
dc.authorscopusid55132713200
dc.authorscopusid7005856240
dc.authorscopusid57217997695
dc.contributor.authorJohnston S.R.D.
dc.contributor.authorToi M.
dc.contributor.authorO'Shaughnessy J.
dc.contributor.authorRastogi P.
dc.contributor.authorCampone M.
dc.contributor.authorNeven P.
dc.contributor.authorHuang C.-S.
dc.date.accessioned2024-06-12T10:25:09Z
dc.date.available2024-06-12T10:25:09Z
dc.date.issued2023
dc.description.abstractBackground: Adjuvant abemaciclib plus endocrine therapy previously showed a significant improvement in invasive disease-free survival and distant relapse-free survival in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2; also known as ERBB2)-negative, node-positive, high-risk, early breast cancer. Here, we report updated results from an interim analysis to assess overall survival as well as invasive disease-free survival and distant relapse-free survival with additional follow-up. Methods: In monarchE, an open-label, randomised, phase 3 trial, adult patients (aged ?18 years) who had hormone receptor-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence with an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 603 sites including hospitals and academic and community centres in 38 countries. Patients were randomly assigned (1:1) by means of an interactive web-based response system (block size of 4), stratified by previous chemotherapy, menopausal status, and region, to receive standard-of-care endocrine therapy of physician's choice for up to 10 years with or without abemaciclib 150 mg orally twice a day for 2 years (treatment period). All therapies were administered in an open-label manner without masking. High-risk disease was defined as either four or more positive axillary lymph nodes, or between one and three positive axillary lymph nodes and either grade 3 disease or tumour size of 5 cm or larger (cohort 1). A smaller group of patients were enrolled with between one and three positive axillary lymph nodes and Ki-67 of at least 20% as an additional risk feature (cohort 2). This was a prespecified overall survival interim analysis planned to occur 2 years after the primary outcome analysis for invasive disease-free survival. Efficacy was assessed in the intention-to-treat population. Safety was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03155997, and is ongoing. Findings: Between July 17, 2017, and Aug 12, 2019, 5637 patients were randomly assigned (5601 [99·4%] were women and 36 [0·6%] were men). 2808 were assigned to receive abemaciclib plus endocrine therapy and 2829 were assigned to receive endocrine therapy alone. At a median follow-up of 42 months (IQR 37–47), median invasive disease-free survival was not reached in either group and the invasive disease-free survival benefit previously reported was sustained: HR 0·664 (95% CI 0·578–0·762, nominal p<0·0001). At 4 years, the absolute difference in invasive disease-free survival between the groups was 6·4% (85·8% [95% CI 84·2–87·3] in the abemaciclib plus endocrine therapy group vs 79·4% [77·5–81·1] in the endocrine therapy alone group). 157 (5·6%) of 2808 patients in the abemaciclib plus endocrine therapy group died compared with 173 (6·1%) of 2829 patients in the endocrine therapy alone group (HR 0·929, 95% CI 0·748–1·153; p=0·50). The most common grade 3–4 adverse events were neutropenia (in 548 [19·6%] of 2791 patients receiving abemaciclib plus endocrine therapy vs 24 [0·9%] of 2800 patients in the endocrine therapy alone group), leukopenia (318 [11·4%] vs 11 [0·4%]), and diarrhoea (218 [7·8%] vs six [0·2%]). Serious adverse events occurred in 433 (15·5%) of 2791 patients receiving abemaciclib plus endocrine therapy versus 256 (9·1%) of 2800 receiving endocrine therapy. There were two treatment-related deaths in the abemaciclib plus endocrine therapy group (diarrhoea and pneumonitis) and none in the endocrine therapy alone group. Interpretation: Adjuvant abemaciclib reduces the risk of recurrence. The benefit is sustained beyond the completion of treatment with an absolute increase at 4 years, further supporting the use of abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative early breast cancer. Further follow-up is needed to establish whether overall survival can be improved with abemaciclib plus endocrine therapy in these patients. Funding: Eli Lilly. © 2023 Elsevier Ltden_US
dc.description.sponsorshipEli Lilly and Company; Royal Marsden NHS Foundation Trust; National Institute for Health and Care Research, NIHRen_US
dc.description.sponsorshipThis study was funded by Eli Lilly. Additional support was provided by the National Institute for Health Research funding to the Royal Marsden and Institute of Cancer Research Biomedical Research Centre. Medical writing and editorial support were provided by Trish Huynh and Eglantine Julle-Daniere, who are both employees of Eli Lilly. All writing, editorial assistance, and statistical analysis were funded by Eli Lilly. All authors were not precluded from accessing the data in the study, and they accept responsibility for the decision to submit for publication. We thank the participants and their families or caregivers for participating in this trial. monarchE would not have been possible without the investigators and their support staff who participated in this work. Finally, the authors are grateful for the time and efforts of the monarchE Executive and Steering Committees.en_US
dc.identifier.doi10.1016/S1470-2045(22)00694-5
dc.identifier.endpage90en_US
dc.identifier.issn1470-2045
dc.identifier.issue1en_US
dc.identifier.pmid36493792en_US
dc.identifier.scopus2-s2.0-85143876322en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage77en_US
dc.identifier.urihttps://doi.org/10.1016/S1470-2045(22)00694-5
dc.identifier.urihttps://hdl.handle.net/20.500.14551/16192
dc.identifier.volume24en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevier Ltden_US
dc.relation.ispartofThe Lancet Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAbemaciclib; Alanine Aminotransferase; Aspartate Aminotransferase; Creatinine; Estrogen Receptor; Gamma Glutamyltransferase; Ki 67 Antigen; Progesterone Receptor; Abemaciclib; Antineoplastic Agent; Epidermal Growth Factor Receptor 2; Abdominal Pain; Adjuvant Chemotherapy; Adult; Arthralgia; Article; Axillary Lymph Node; Breast Computed Tomography; Cancer Adjuvant Therapy; Cancer Diagnosis; Cancer Patient; Cancer Radiotherapy; Cancer Recurrence; Causality; Clinical Outcome; Clinical Practice; Constipation; Controlled Study; Diarrhea; Disease Free Survival; Distant Recurrence Free Survival; Dizziness; Drug Efficacy; Drug Safety; Drug Withdrawal; Fatigue; Female; Fever; Follow Up; Gastrointestinal Disease; High Risk Patient; Histopathology; Hormonal Therapy; Hormone Receptor Negative Breast Cancer; Hormone Receptor Positive Breast Cancer; Human; Hypertension; Hypokalemia; Infection; Interstitial Lung Disease; Leukopenia; Lung Embolism; Lymphedema; Lymphocytopenia; Male; Metastatic Breast Cancer; Neutropenia; Neutrophil Count; Outcome Assessment; Overall Survival; Patient-Reported Outcome; Phase 3 Clinical Trial; Phenotype; Progression Free Survival; Randomized Controlled Trial; Rash; Thrombocytopenia; Tumor Invasion; Tumor Volume; Urinary Tract Infection; Vaccination; Venous Thromboembolism; Vomiting; Adolescent; Breast Tumor; Clinical Trial; Diarrhea; Genetics; Metabolism; Pathology; Tumor Recurrence; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Diarrhea; Female; Humans; Male; Neoplasm Recurrence, Local; Receptor, Erbb-2en_US
dc.titleAbemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trialen_US
dc.typeArticleen_US

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