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DOI: 10.1055/a-2238-3153
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:
08 February 2024
© 2024. The Author(s). This is an open access article published by Thieme 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/).
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