Subscribe to RSS
DOI: 10.1055/a-2562-8469
Die adjuvante zielgerichtete Behandlung des frühen hormonrezeptorpositiven HER2-negativen Mammakarzinoms: Olaparib, Abemaciclib oder Ribociclib – was, wie und für wen?
Article in several languages: English | deutsch
Zusammenfassung
Das Mammakarzinom (BC) ist mit etwa 70000 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.
Publication History
Received: 28 November 2024
Accepted after revision: 15 March 2025
Article published online:
22 April 2025
© 2025. 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/).
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References/Literatur
- 1 Deutsche Krebsgesellschaft (DKG). Wie häufig ist Brustkrebs?. Accessed January 02, 2022 at: https://www.krebsgesellschaft.de/onko-internetportal/basis-informationen-krebs/krebsarten/brustkrebs-definition-und-haeufigkeit.html
- 2 Dannehl D, Volmer LL, Weiss M. et al. Feasibility of Adjuvant Treatment with Abemaciclib—Real-World Data from a Large German Breast Center. J Pers Med 2022; 12: 382
- 3 Caswell-Jin JL, Sun LP, Munoz D. et al. Analysis of Breast Cancer Mortality in the US—1975 to 2019. JAMA 2024; 331: 233
- 4 Rastogi P, O’Shaughnessy J, Martin M. et al. Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes. J Clin Oncol 2024; 42: 987-993
- 5 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
- 6 Slamon D, Lipatov O, Nowecki Z. et al. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med 2024; 390: 1080-1091
- 7 European Medicines Agency (EMA). Verzenios. Accessed February 25, 2025 at: https://www.ema.europa.eu/en/medicines/human/EPAR/verzenios
- 8 Johnston SRD, Toi M, O’Shaughnessy J. et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol 2023; 24: 77-90
- 9 European Medicines Agency (EMA). Kisqali – opinion on variation to marketing authorisation. Accessed October 28, 2024 at: https://www.ema.europa.eu/en/medicines/human/variation/kisqali
- 10 Slamon DJ, Fasching PA, Hurvitz S. et al. Rationale and trial design of NATALEE: a Phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2- early breast cancer. Ther Adv Med Oncol 2023; 15: 17588359231178125
- 11 Amin MB, Greene FL, Edge SB. et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017; 67: 93-99
- 12 Fasching PA, Stroyakovskiy D, Yardley D. et al. LBA13 Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (Pts) with HR+/HER2− early breast cancer (EBC): 4-year outcomes from the NATALEE trial. Ann Oncol 2024; 35: S1207
- 13 Slamon D, Yardley DA, Hortobagyi G. Ribociclib plus Endocrine Therapy in Early Breast Cancer. Reply. N Engl J Med 2024; 390: 2221-2222
- 14 Marmé F, Lederer B, Blohmer JU. et al. Utility of the CPS + EG staging system in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with neoadjuvant chemotherapy. Eur J Cancer 2016; 53: 65-74
- 15 Geyer CE, Garber JE, Gelber RD. et al. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol 2022; 33: 1250-1268
- 16 Ramaswami R, Uldrick TS. Reflecting the Real World of Cancer Care – The Impact of Broadening Trial Eligibility. NEJM Evid 2024; 3: EVIDe2400011
- 17 U.S. Food & Drug Administration (FDA). FDA approves ribociclib with an aromatase inhibitor and ribociclib and letrozole co-pack for early high-risk breast cancer. Accessed October 27, 2024 at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ribociclib-aromatase-inhibitor-and-ribociclib-and-letrozole-co-pack-early-high-risk-0
- 18 Schäffler H, Mergel F, Pfister K. et al. The Clinical Relevance of the NATALEE Study: Application of the NATALEE Criteria to a Real-World Cohort from Two Large German Breast Cancer Centers. Int J Mol Sci 2023; 24: 16366
- 19 Kanjanapan Y, Anderson W, Smith M. et al. Real-World Analysis of Breast Cancer Patients Qualifying for Adjuvant CDK4/6 Inhibitors. Clin Breast Cancer 2025; 25: e159-e169.e2
- 20 Tauber N, Hilmer L, Dannehl D. et al. Oral Maintenance Therapy in Early Breast Cancer—How Many Patients Are Potential Candidates?. Cancers 2025; 17: 145
- 21 Dannehl D, Engler T, Volmer LL. et al. Which Patients Do We Need to Test for BRCA1/2 Mutation? Feasibility of Adjuvant Olaparib Treatment in Early Breast Cancer-Real-World Data from Two Large German Breast Centers. Cancers (Basel) 2023; 15: 3847
- 22 Brustkrebsrisiko, Genetik und Prävention. Accessed November 25, 2024 at: https://www.ago-online.de/fileadmin/ago-online/downloads/_leitlinien/kommission_mamma/2022/Einzeldateien/AGO_2022D_02_Brustkrebsrisiko_Genetik_und_Praevention.pdf
- 23 Ladoire S, Mamguem Kamga A, Galland L. et al. Real-world prevalence, treatment and survival of “high risk” early breast cancer, with mandatory testing of gBRCA1/2 mutation according to the OlympiA trial inclusion criteria: Data from a population-based registry. Breast 2024; 78: 103789
- 24 Mavaddat N, Barrowdale D, Andrulis IL. et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: Results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomarkers Prev 2012; 21: 134-147
- 25 Drowne T, Armgardt E, Svoboda A. Real-world experience of abemaciclib for adjuvant and metastatic breast cancer. J Oncol Pharm Pract 2025; 31: 141-146
- 26 Neralla H, Herring K, Stevens A. et al. Real-world Data on Safety Outcome with Treatment of Adjuvant Abemaciclib plus Endocrine Therapy in High-risk Early Hormone-positive, HER2-negative Breast Cancer Patients. Clin Oncol 2024; 36: e110-e111
- 27 Goetz MP, Cicin I, Testa L. et al. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study. NPJ Breast Cancer 2024; 10: 34
- 28 Kristensen KB, Thomsen IMN, Berg T. et al. Dose modifications of ribociclib and endocrine therapy for treatment of ER+ HER2− metastatic breast cancer. Breast Cancer Res Treat 2021; 188: 799-809
- 29 Eisen A, Somerfield MR, Accordino MK. et al. Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update. J Clin Oncol 2022; 40: 787-800
- 30 Friedl TWP, Fehm T, Müller V. et al. Prognosis of Patients With Early Breast Cancer Receiving 5 Years vs 2 Years of Adjuvant Bisphosphonate Treatment: A Phase 3 Randomized Clinical Trial. JAMA Oncol 2021; 7: 1149-1157
- 31 Oliveira LJC, Rosa DD, Katz A. et al. Cancer outcomes from a real-world cohort of patients eligible for adjuvant CDK4/6 inhibitors but without genomic risk for chemotherapy: A GBECAM multicenter retrospective study. J Clin Oncol 2024; 42: 540-540
- 32 Caswell-Jin JL, Freedman RA, Hassett MJ. et al. Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer—CDK4/6 Inhibitors: ASCO Rapid Guideline Update Clinical Insights. JCO Oncol Pract 2025; 21: 287-291
- 33 Abe O, Abe R, Enomoto K. et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771-784
- 34 Pistilli B, Lohrisch C, Sheade J. et al. Personalizing Adjuvant Endocrine Therapy for Early-Stage Hormone Receptor-Positive Breast Cancer. Am Soc Clin Oncol Educ Book 2022; 42: 60-72
- 35 Ditsch N, Wöcke A, Untch M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2022. Breast Care 2022; 17: 403-420
- 36 Bradley R, Burrett J, Clarke M. et al. Aromatase inhibitors versus tamoxifen in early breast cancer: Patient-level meta-analysis of the randomised trials. Lancet 2015; 386: 1341-1352
- 37 Giacchetti S, Laas E, Bachelot T. et al. Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial. EBioMedicine 2024; 104: 105141
- 38 Nabieva N, Fasching PA. Endocrine Treatment for Breast Cancer Patients Revisited—History, Standard of Care, and Possibilities of Improvement. Cancers 2021; 13: 5643
- 39 Sparano JA, Gray RJ, Ravdin PM. et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med 2019; 380: 2395
- 40 AGO – Die Arbeitsgemeinschaft Gynäkologische Onkologie. Kommission Mamma | Leitlinien & Empfehlungen | Leitlinien & Stellungnahmen. Accessed July 21, 2024 at: https://www.ago-online.de/leitlinien-empfehlungen/leitlinien-empfehlungen/kommission-mamma
- 41 Lukac S, Griewing S, Leinert E. et al. ChatGPT, Google, or PINK? Who Provides the Most Reliable Information on Side Effects of Systemic Therapy for Early Breast Cancer?. Clin Pract 2024; 15: 8
- 42 Duan J, Tao J, Zhai M. et al. Anticancer drugs-related QTc prolongation, torsade de pointes and sudden death: current evidence and future research perspectives. Oncotarget 2018; 9: 25738
- 43 De Placido S, Gallo C, De Laurentiis M. et al. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol 2018; 19: 474-485
- 44 Francis PA, Pagani O, Fleming GF. et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379: 122-137
- 45 Coleman R, Gray R, Powles T. et al. Adjuvant bisphosphonate treatment in early breast cancer: Meta-analyses of individual patient data from randomised trials. Lancet 2015; 386: 1353-1361
- 46 Fachinfo Lynparza. Accessed November 25, 2024 at: https://www.fachinfo.de/fi/pdf/021996
- 47 Fachinfo Kisqali. Accessed November 25, 2024 at: https://www.fachinfo.de/fi/pdf/021677
- 48 Fachinfo Verzenios. Accessed November 25, 2024 at: https://www.fachinfo.de/fi/pdf/022221