Subscribe to RSS
DOI: 10.1055/a-2305-1185
Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care – The PreFace Study
Langfristige Nachbeobachtung und Sicherheit im klinischen Alltag bei Patientinnen nach Upfront-Therapie mit Letrozol zur Behandlung von Brustkrebs im Frühstadium – die PreFace-StudieSupported by: Novartis Germany GmbHClinical Trial: Registration number (trial ID): NCT01908556, Trial registry: ClinicalTrials.gov (http://www.clinicaltrials.gov/), Type of Study: prospective open label phase IV clinical trial
Abstract
Introduction
Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore, this study analyzed the prognosis and patient characteristics of postmenopausal patients selected for a five-year upfront letrozole therapy.
Patients and Methods
From 2009 to 2011, 3529 patients were enrolled into the adjuvant phase IV PreFace clinical trial (NCT01908556). Postmenopausal hormone receptor-positive BC patients, for whom an upfront five-year therapy with letrozole (2.5 mg/day) was indicated, were eligible. Disease-free survival (DFS), overall survival (OS) and safety in relation to patient and tumor characteristics were assessed.
Results
3297 patients started letrozole therapy. The majority of patients (n = 1639, 57%) completed the five-year treatment. 34.5% of patients continued with endocrine therapy after the mandated five-year endocrine treatment. Five-year DFS rates were 89% (95% CI: 88–90%) and five-year OS rates were 95% (95% CI: 94–96%). In subgroup analyses, DFS rates were 83%, 84% and 78% for patients with node-positive disease, G3 tumor grading, and pT3 tumors respectively. The main adverse events (any grade) were pain and hot flushes (66.8% and 18.3% of patients).
Conclusions
The risk profile of postmenopausal BC patients selected for a five-year upfront letrozole therapy showed a moderate recurrence and death risk. However, in subgroups with unfavorable risk factors, prognosis warrants an improvement, which might be achieved with novel targeted therapies.
Zusammenfassung
Einleitung
Die adjuvante Behandlung von Patientinnen mit Brustkrebs im Frühstadium sollte eine Therapie mit einem Aromatasehemmer (AH) miteinschließen. Patientinnen mit einem hohen Rezidivrisiko profitieren besonders von einer Upfront-Therapie mit einem AH, die sich über einen Mindestzeitraum von 5 Jahren erstreckt. Dennoch ist nicht viel über die Selektion geeigneter Patientinnen in dieser Population in der Praxis bekannt. Diese Studie hat deshalb die Prognosen und Charakteristika von postmenopausalen Patientinnen, die für eine Upfront-Therapie mit Letrozol über 5 Jahre ausgewählt wurden, analysiert.
Patientinnen und Methoden
Zwischen 2009 und 2011 nahmen 3529 Patientinnen an der adjuvanten klinischen Phase-IV-PreFace-Studie (NCT01908556) teil. Eingeschlossen wurden postmenopausale hormonrezeptorpositive Brustkrebspatientinnen mit Indikation für eine 5-jährige Upfront-Therapie mit Letrozol (2,5 mg/Tag). Beurteilt wurden krankheitsfreies Überleben (KFÜ), Gesamtüberleben (GÜ) und Sicherheit in Abhängigkeit von den Patientinnen- und Tumorcharakteristika.
Ergebnisse
Insgsamt begannen 3297 Patientinnen mit einer Letrozol-Therapie. Die Mehrheit der Patientinnen (n = 1639, 57%) haben die 5-jährige Behandlung abgeschlossen. Nach Beendigung der angeordneten 5-jährigen endokrinen Behandlung machten 34,5% der Patientinnen mit einer endokrinen Therapie weiter. Die 5-jährige KFÜ-Rate betrug 89% (95%-KI: 88–90%) und die 5-jährige GÜ-Rate war 95% (95%-KI: 94–96%). Bei der Subgruppenanalyse betrugen die KFÜ-Raten 83%, 84% resp. 78% für Patientinnen mit jeweils nodal-positivem Brustkrebs, Tumorgrad G3 bzw. pT3-Tumoren. Zu den wichtigsten unerwünschten Ereignissen (aller Schweregrade) gehörten Schmerzen sowie Hitzewallungen (die jeweils bei 66,8% bzw. 18,3% der Patientinnen auftraten).
Schlussfolgerungen
Die Analyse des Risikoprofils von postmenopausalen Brustkrebspatientinnen, die für eine 5-jährige Upfront-Therapie mit Letrozol ausgewählt wurden, zeigte ein mäßiges Rezidiv- und Sterberisiko. Aber bei Untergruppen mit ungünstigen Risikofaktoren rechtfertigt die Prognose die Suche nach Verbesserungen, die mithilfe neuartiger zielgerichteter Therapien erreicht werden können.
Publication History
Received: 17 November 2023
Accepted after revision: 21 December 2023
Article published online:
23 May 2024
© 2024. The Author(s). This article was originally published by Thieme in Geburtsh Frauenheilk 2024; 84: 185–195 as an open access article under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Breast Cancer Version 3.2022. 2022 Accessed July 18, 2022 at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
- 2 Ditsch N, Kolberg-Liedtke C, Friedrich M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2021. Breast Care (Basel) 2021; 16: 214-227
- 3 Goss PE, Ingle JN, Pritchard KI. et al. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol 2013; 31: 1398-1404
- 4 Boccardo F, Rubagotti A, Puntoni M. et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial. J Clin Oncol 2005; 23: 5138-5147
- 5 Jakesz R, Jonat W, Gnant M. et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 2005; 366: 455-462
- 6 Kaufmann M, Jonat W, Hilfrich J. et al. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol 2007; 25: 2664-2670
- 7 Baum M, Buzdar A, Cuzick J. et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer 2003; 98: 1802-1810
- 8 Coombes RC, Hall E, Gibson LJ. et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med 2004; 350: 1081-1092
- 9 van de Velde CJ, Rea D, Seynaeve C. et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet 2011; 377: 321-331
- 10 Dubsky PC, Jakesz R, Mlineritsch B. et al. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 2012; 30: 722-728
- 11 Baum M, Budzar AU, Cuzick J. et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359: 2131-2139
- 12 Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386: 1341-1352
- 13 Schneeweiss A, Ettl J, Lüftner D. et al. Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer – Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany. Breast 2020; 54: 88-95
- 14 Harbeck N, Rastogi P, Martin M. monarchE Committee Members. et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol 2021; 32: 1571-1581
- 15 Fasching PA, Gass P, Häberle L. et al. Prognostic effect of Ki-67 in common clinical subgroups of patients with HER2-negative, hormone receptor-positive early breast cancer. Breast Cancer Res Treat 2019; 175: 617-625
- 16 Slamon DJ, Stroyakovskiy D, Yardley DA. et al. Phase III NATALEE trial of ribociclib + endocrine therapy as adjuvant treatment in patients with HR+/HER2− early breast cancer. ASCO Annual Meeting 2023; 2023: LBA500
- 17 Allison KH, Hammond MEH, Dowsett M. et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update. Arch Pathol Lab Med 2020; 144: 545-563
- 18 Wolff AC, Hammond MEH, Allison KH. et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 2018; 36: 2105-2122
- 19 Johnston SRD, Harbeck N, Hegg R. monarchE Committee Members and Investigators. et al. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol 2020; 38: 3987-3998
- 20 Ingle JN, Cairns J, Suman VJ. et al. Anastrozole has an Association between Degree of Estrogen Suppression and Outcomes in Early Breast Cancer and is a Ligand for Estrogen Receptor alpha. Clin Cancer Res 2020; 26: 2986-2996
- 21 Ingle JN, Xie F, Ellis MJ. et al. Genetic Polymorphisms in the Long Noncoding RNA MIR2052HG Offer a Pharmacogenomic Basis for the Response of Breast Cancer Patients to Aromatase Inhibitor Therapy. Cancer Res 2016; 76: 7012-7023
- 22 Fasching PA, Yadav S, Hu C. et al. Mutations inBRCA1/2and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis. J Clin Oncol 2021; 39: 1619-1630
- 23 Tutt ANJ, Garber JE, Kaufman B. et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med 2021; 384: 2394-2405
- 24 Tutt ANJ, Garber J, Gelber RD. et al. VP1–2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer. Ann Oncol 2022;
- 25 Slamon DJ, Fasching PA, Patel R. et al. NATALEE: Phase III study of ribociclib (RIBO) + endocrine therapy (ET) as adjuvant treatment in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) early breast cancer (EBC). J Clin Oncol 2019; 37 (Suppl. 15) TPS597
- 26 clinicaltrials.gov. NCT03701334, A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2− Early Breast Cancer (NATALEE). NIH U.S. National Library of Medicine. 2018 Accessed November 07, 2020 at: https://clinicaltrials.gov/ct2/show/NCT03701334