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CDK4/6-Inhibitoren beim Mammakarzinom

CDK4/6 inhibitors in breast cancer

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best practice onkologie Aims and scope

Zusammenfassung

Für Palbociclib, Ribociclib und Abemaciclib, Inibitoren der Cyclin-D-Kinase 4/6 (CDK4/6), wurde in großen Studienprogrammen eine signifikante Verlängerung des progressionsfreien Überlebens in der Behandlung des metastasierten hormonrezeptorpositiven, für humanen epidermalen Wachstumsfaktorrezeptor 2 (HER2) negativen Mammakarzinoms nachgewiesen. Seit der Zulassung von Palbociclib und Ribociclib in Deutschland gehören die Substanzen in Kombination mit einer antihormonellen Therapie zur Standardbehandlung in der Erst-, aber auch Zweitlinientherapie. Der dritte CDK-4/6-Inhibitor Abemaciclib, in den USA bereits zugelassen, wird noch in diesem Jahr in Deutschland zugelassen werden. Die Nebenwirkungen, allen voran die Neutropenie, lassen sich durch Dosisreduzierungen und Dosisunterbrechungen gut im Alltag managen. Das damit verbundene intensivere Therapiemonitoring muss präzise eingehalten werden, um die Therapie im Sinne einer Erhaltungstherapie applizieren zu können. Aktuell laufen bereits die ersten Studien in der neo-/adjuvanten Situation, um den Überlebensvorteil aus der metastasierten Situation in die frühe Behandlungsphase übertragen zu können. Das Ziel dieser Übersichtsarbeit ist es, die Wirkungsweise, die Effektivität und die Nebenwirkungen der CDK4/6-Inhibitoren zu erläutern und sie in einen aktuellen klinischen Kontext zu setzen.

Abstract

The cyclin-dependent kinase (CDK)4/6 inhibitors palbociclib, ribociclib, and abemaciclib have demonstrated significant improvements in progression-free survival in numerous clinical trials in metastasized hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Since palbociclib and ribociclib were approved in Germany, CDK4/6 inhibitors in combination with antihormonal therapy have been a standard treatment in first- and also in second-line therapy. Abemaciclib, the third CDK4/6, inhibitor will be approved in Germany this year. Side effects, particularly neutropenia, are well managed in daily routine by dose reductions and dose interruptions. The necessary intensive treatment monitoring has to be adhered to precisely, in order to administer treatment in the form of a well-tolerated maintenance therapy. Several clinical trials in the neo-/adjuvant setting are currently in progress, in order to transfer the survival advantage from the metastasized situation into early breast cancer. The aim of this article is to elucidate the mode of action, efficacy, and side effects of the CDK4/6 inhibitors, and to put them in a current clinical context.

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Authors and Affiliations

  1. Klinik für Gynäkologie und Geburtshilfe, AGAPLESION Markus Krankenhaus, Wilhelm-Epstein-Straße 4, 60431, Frankfurt am Main, Deutschland

    Marc Thill & Lena Traub

  2. Klinik für Frauenheilkunde und Geburtshilfe, Helios Klinikum Krefeld, Krefeld, Deutschland

    Michael Friedrich

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  1. Marc Thill
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  2. Lena Traub
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Correspondence to Marc Thill.

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Interessenkonflikt

M. Thill gibt an, Reisekostenerstattung und Berater- und Vortraghonorare von AstraZeneca, Pfizer, Lilly und Novartis erhalten zu haben. L. Traub gibt an, Reisekostenerstattung von Pfizer erhalten zu haben. M. Friedrich gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Thill, M., Traub, L. & Friedrich, M. CDK4/6-Inhibitoren beim Mammakarzinom. best practice onkologie 13, 298–307 (2018). https://doi.org/10.1007/s11654-018-0105-7

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  • DOI: https://doi.org/10.1007/s11654-018-0105-7

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