Austrian treatment algorithms 2025: CDK 4/6 inhibitors in the adjuvant therapy of HR+/HER2− early breast cancer
Austrian breast cancer expert group (Austrian treatment algorithms) · 2026 · Austria
Source and licence
- Authors
- Rupert Bartsch, Clemens Dormann, Daniel Egle et al.
- Title
- Austrian treatment algorithms 2025: CDK 4/6 inhibitors in the adjuvant therapy of HR+/HER2− early breast cancer
- Journal
- Wiener Klinische Wochenschrift, 2026
- Licence
- CC BY 4.0
- Changes
- Verbatim excerpts; formatting adapted
Full text retrieved 2026-10-27 from Europe PMC · PMC13672391
Licence statement of the original publication
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
This page reproduces excerpts of the original publication; the original is authoritative. It has not been reviewed by a physician, does not state a recommendation of Medelix and does not replace medical advice. The guideline may have been updated since.
Open the original publication →Full text on Europe PMC
Recommendations
Verbatim, with grade of recommendation or strength of consensus where given.
Tolerability
- Diarrhea is the most common side effect of abemaciclib. Although diarrhea was generally low grade (grade 1/2: 76%) in the monarchE trial, it led to discontinuation in 5.3% of patients in the abemaciclib arm, as grade 2 diarrhea might interfere with activities of daily living [47].
- In the NATALEE trial 62.1% of the patients in the ribociclib-NSAI arm experienced neutropenia. Neutropenia was also the most frequent event of grade 3 or higher in the combination arm, occurring in 43.8% of the patients (vs. 0.8% in the NSAI arm). Liver-related AEs were observed with greater frequency of 25.4% (vs. 10.6% in the NSAI arm) and severity (grade 3/4: 8.3% vs. 1.5%) among patients treated with ribociclib and an NSAI compared to those receiving an NSAI alone. Liver-related adverse events emerged as the principal cause of treatment discontinuation in the ribociclib-treated population, resulting in permanent cessation of therapy in 8.9% of patients, mostly occurring early during treatment. These findings underscore the need for hepatic monitoring during ribociclib therapy in the early breast cancer setting. Prolongation of the QT interval is another known side effect of ribociclib and occurred in 5.2% (any grade) of the patients in the ribociclib-NSAI arm (vs. 1.2% in the NSAI arm). A total of 477 patients (18.9%) discontinued treatment with ribociclib due to AEs, with most discontinuations occurring early in the treatment course (median time to discontinuation: 4 months) [29].
Summary of recommendations
- CDK4/6 inhibitor (abemaciclib preferred in patients matching monarchE criteria due to significant OS improvement) plus endocrine therapy
- Ribociclib + AI, e.g., in younger patients or high proliferation index. Post hoc analysis suggests potential efficacy for off-label abemaciclib use in the cohort 2 (N1, < T3/G3) population [47]
- Ribociclib may be preferable due to lower GI toxicity
- Individualized decision; consider de-escalation or extended ET only
Abstract
Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer (eBC) represents the most common breast cancer subtype, with relevant recurrence risks despite optimal endocrine therapy (ET) and locoregional treatment. Long-term data from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) demonstrate that recurrence risk remains substantial, with outcomes strongly influenced by nodal burden, tumor size, and biological parameters.
Advances in systemic therapy, including optimized endocrine strategies, chemotherapy, bone-modifying agents, PARP inhibitors for patients harboring germline BRCA 1/2-mutations, have significantly improved survival, yet recurrence remains a clinically relevant challenge, including for node-negative patients harboring additional biological risk features.
The introduction of adjuvant CDK4/6 inhibitors represents an important therapeutic development. Abemaciclib (monarchE) has demonstrated sustained improvements in invasive disease-free survival (IDFS), distant relapse-free survival (DRFS), and a statistically significant overall survival (OS) benefit at 7 years. Ribociclib (NATALEE) demonstrated statistically significant IDFS improvement across a broader clinical risk spectrum, including selected node-negative disease.
However, these advances must be considered in the context of distinct toxicity, treatment burden, and substantial additional healthcare system costs. Although emerging evidence supports treatment intensification with CDK4/6 inhibitors in certain settings, uncertainty persists regarding which patient subgroups derive sufficient benefit to justify routine use from both a clinical and health-economic perspective.
Further clarification is expected from ongoing randomized studies and real-world evidence, as this paper aims to provide a structured, evidence-based overview of the current standard of knowledge and to support Austrian breast cancer specialists in navigating treatment decisions regarding adjuvant CDK4/6 inhibitor use.
Contents of the original publication
The section headings of the original.
- Introduction
- CDK4/6 inhibitors in HR+/HER2− eBC
- Tolerability
- Quality of life
- Distinguishing parameters for optimized treatment selection
- Discussion and recommendations: adjuvant use of CDK4/6 inhibitors in HR+/HER2− early breast cancer
- Trial inclusion criteria
- Summary of benefits of both substances
- Burden on patients
- Burden on healthcare systems
- Patient selection: risk assessment in intermediate-risk populations
- Recommendation from the expert discussions
- Recommendations for treatment management based on expert discussions
- Patient capacity and infrastructure requirements
- Practical considerations
- Therapy matching and choice of agent
- Summary of recommendations
- Conclusion
- Future outlook
A question about this guideline?
Medelix answers clinical questions from guidelines and studies – every statement with its source.
Are you the rights holder and object to this reproduction? Write to contact@medelix.ai and we will take the page down promptly. Imprint