Die adjuvante zielgerichtete Behandlung des frühen hormonrezeptorpositiven HER2-negativen Mammakarzinoms: Olaparib, Abemaciclib oder Ribociclib – was, wie und für wen?

Zusammenfassung

Das Mammakarzinom (BC) ist mit etwa 70 000 Neuerkrankungen jährlich weiterhin die häufigste Krebserkrankung. Der häufigste Typ ist das hormonrezeptorpositive, HER2-negative BC (HR+/HER2−), das etwa 70 % der Fälle des frühen BC (eBC) ausmacht. Insbesondere dank neuer medikamentöser Entwicklungen hat sich das Überleben von Patient*innen mit eBC in den letzten Jahren deutlich verbessert. Neben etablierten endokrinen Therapieoptionen (ET), wie Tamoxifen, Aromatasehemmern (AI) und GnRH-Analoga, stehen inzwischen mit den CDK4/6-Inhibitoren (Abemaciclib und Ribociclib) und dem PARP-Inhibitor (Olaparib) zusätzliche Behandlungsansätze zur Verfügung. Um die Anwendung im klinischen Alltag zu erleichtern, fasst dieser Artikel aktuelle und praxisrelevante Informationen zu diesen Medikamenten zusammen.

Abemaciclib wurde 2022 für die adjuvante Behandlung des HR+/HER2− eBC mit positiven Lymphknoten zugelassen. In der MonarchE-Studie zeigte die Hinzunahme von Abemaciclib zu ET eine Verbesserung des krankheitsfreien Überlebens (iDFS) nach 5 Jahren um 7,6 % bei Patientinnen mit hohem Rückfallrisiko. Ribociclib, ein weiterer CDK4/6-Inhibitor, erhielt kürzlich die Zulassung basierend auf der NATALEE-Studie. In Kombination mit nicht steroidalen AIs zeigte Ribociclib einen signifikanten Benefit im iDFS von 4,9 % nach 4 Jahren bei nodal positiven und nodal negativen Patientinnen mit erhöhtem Rezidivrisiko. Der PARP-Inhibitor Olaparib kann bei Patientinnen mit BRCA-Keimbahnmutation und HR+/HER2− eBC mit hohem Rezidivrisiko (CPS-EG Score ≥ 3) eingesetzt werden. Die Zulassungsstudie OlympiA zeigte nach 4 Jahren einen Vorteil von 7,3 % im iDFS sowie einen Vorteil im Gesamtüberleben von 3,4 %.

Zusammenfassend erweitern zielgerichtete Therapien das Spektrum der adjuvanten Behandlungsmöglichkeiten für Patientinnen mit HR+/HER2− eBC mit erhöhtem Rezidivrisiko. Die behandelnden Ärztinnen und Ärzte stehen zunehmend vor der Herausforderung, die optimale Therapie für die Patientin bzw. den Patienten zu selektieren. Dafür ist es essenziell, sorgfältig die potenziellen Nebenwirkungen und den Benefit durch die Therapie individuell abzuwägen.

Abstract

With around 70 000 new cases every year, breast cancer (BC) continues to be the most prevalent form of cancer. Hormone receptor-positive, HER2-negative (HR+/HER2−) BC is the most common type and accounts for around 70 % of cases of early BC (eBC). The development of new drugs in recent years has significantly improved the survival of patients with eBC. Alongside established endocrine therapy (ET) options such as tamoxifen, aromatase inhibitors (AI), and GnRH analogs, additional treatment options such as CDK 4/6 inhibitors (abemaciclib and ribociclib) and the PARP inhibitor (olaparib) are now also available. To facilitate their use in clinical practice, this article provides a summary of the current information on the use of these drugs in clinical practice.

Abemaciclib was approved for the adjuvant treatment of HR+/HER2− eBC in cases with positive lymph node involvement in 2022. The MonarchE trial showed that the addition of abemaciclib to ET improved invasive disease-free survival (iDFS) after 5 years by around 7.6 % in patients with a high risk of recurrence. Ribociclib, another CDK4/6 inhibitor, was recently approved based on the results of the NATALEE trial. When combined with non-steroidal AIs, ribociclib showed a significant iDFS benefit of 4.9 % after 4 years in node-positive and node-negative patients with a high risk of recurrence. The PARP inhibitor olaparib may be used to treat patients with BRCA germline mutation and HR+/HER2− eBC and a high risk of recurrence (CPS-EG score ≥ 3). The OlympiA approval study showed an iDFS benefit of 7.3 % after four years and a benefit of 3.4 % for overall survival.

In summary, targeted therapies are expanding the range of adjuvant treatment options for patients with HR+/HER2−eBC and a higher risk of recurrence. Treating physicians are increasingly facing the challenge of choosing the optimal therapy for their patients. To do so, it is essential to carefully weigh up potential side effects against the expected benefit of treatment on a case-by-case basis.

Schlüsselwörter

Abemaciclib - Ribociclib - Olaparib - Mammakarzinom - adjuvante Therapie

Keywords

Abemaciclib - Ribociclib - Olaparib - breast cancer - adjuvant therapy

Publikationsverlauf

Eingereicht: 28. November 2024

Angenommen nach Revision: 15. März 2025

Artikel online veröffentlicht:
24. September 2025

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