Trastuzumab Administration in Patients with Metastatic Breast Cancer – Experience of a Large University Breast Center

Abstract

Background: Administered either alone or in combination with various cytostatic, endocrine or targeted therapies, trastuzumab significantly improves the prognosis of patients with HER2-positive breast cancer. As trastuzumab is effective across multiple lines of therapy in the metastatic setting (treatment beyond progression: TBP), it is often administered over a long period of time. The aim of this study was to evaluate the tolerability and clinical practice of long-term trastuzumab administration (> 1 year) in metastatic breast cancer patients treated in a large university breast center. Methods: Metastatic breast cancer patients who received at least 18 cycles of trastuzumab administered every three weeks at the University Gynecological Hospital of Tuebingen between 1999 and 2012 were included in this retrospective study. Typical combination drugs, side effects, and the impact of administration on left ventricular ejection fraction (LVEF) were investigated. Results: 72 patients were eligible for inclusion in the study. The mean number of administrations was 50.14 (SD: 27.51). In 53 patients the principle of TBP was followed across an average of 2.4 therapy lines. Classic cardiac risk factors were present at the beginning of trastuzumab treatment in 34 patients (47 %). Seven patients (10 %) experienced a decrease in LVEF during treatment, 9 patients (13 %) had hypersensitivity reactions. Treatment was discontinued in two patients due to side effects (1 × progressive LVEF decrease, 1 × intolerance). Summary: The administration of trastuzumab across multiple lines of therapy was generally tolerated well. Cardiac risk factors were not a limiting factor. If regular cardiac monitoring is done, trastuzumab appears not only to improve survival but also helps preserve the quality of life of patients with HER2-positive metastatic breast cancer.

Zusammenfassung

Hintergrund: Trastuzumab trägt sowohl als Monotherapeutikum sowie in Kombination mit verschiedenen zytostatischen, endokrinen und zielgerichteten Therapien maßgeblich zur Prognoseverbesserung von Patientinnen mit HER2-positivem Mammakarzinom bei. Da Trastuzumab in der metastasierten Situation über mehrere Therapielinien hinweg wirksam ist (treatment beyond progression: TBP), wird es häufig über einen langen Zeitraum verabreicht. Ziel der vorliegenden Arbeit ist die Evaluation der Verträglichkeit und klinischen Praxis der Trastuzumab-Langzeittherapie (> 1 Jahr) des metastasierten Mammakarzinoms an einem großen universitären Brustzentrum. Methoden: In einer retrospektiven Studie wurden klinische Daten von Patientinnen erfasst, die an der Universitäts-Frauenklinik Tübingen zwischen 1999 und 2012 mindestens 18 3-wöchentliche Gaben Trastuzumab in der metastasierten Situation erhielten. Hierbei wurden insbesondere typische Kombinationspräparate, Nebenwirkungen und der Einfluss der Behandlung auf die linksventrikuläre Ejektionsfraktion (LVEF) untersucht. Ergebnisse: 72 Patientinnen konnten in die Analyse eingeschlossen werden. Die durchschnittliche Anzahl der Applikationen betrug 50,14 (Standardabweichung: 27,51). Bei 53 Patientinnen wurde das TBP-Prinzip im Durchschnitt über 2,4 Therapielinien hinweg angewandt. Bei 34 Patientinnen (47 %) waren zu Beginn der Trastuzumab-Therapie klassische kardiale Risikofaktoren vorhanden. Sieben Patientinnen (10 %) hatten während der Behandlung einen LVEF-Abfall, Unverträglichkeitsreaktionen fanden sich in 9 (13 %) Fällen. Die Behandlung wurde aufgrund von Nebenwirkungen bei 2 Patientinnen abgebrochen (1 × progredienter LVEF-Abfall, 1 × Unverträglichkeit). Zusammenfassung: Die Anwendung von Trastuzumab über mehrere Therapielinien hinweg wurde insgesamt gut vertragen. Kardiale Risikofaktoren waren bei der Langzeitanwendung kein limitierender Faktor. Unter regelmäßiger kardiologischer Kontrolle scheint Trastuzumab daher nicht nur zu einem verbesserten Überleben, sondern ebenso zum Erhalt der Lebensqualität von Patientinnen mit HER2-positivem metastasiertem Mammakarzinom beizutragen.

Key words

breast cancer - Her-2/neu - metastasis - chemotherapy - trastuzumab

Schlüsselwörter

Mammakarzinom - Her-2/neu - Metastasierung - Chemotherapie - Trastuzumab

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