The MonarchE study

During ESMO 2025, the pivotal MonarchE trial provided the first evidence of an overall survival (OS) benefit with a CDK4/6 inhibitor in the adjuvant treatment of hormone receptor–positive, HER2-negative, high-risk early breast cancer. After seven years of follow-up, the study demonstrated that adding two years of abemaciclib to standard endocrine therapy leads to a significant improvement in OS (7-year OS rate: 86.8% vs. 85.0%; HR[95%CI]: 0.842[0.722-0.981]; p= 0.0273). In this video, Prof Patrick Neven, gynecological oncologist at the University Hospitals Leuven, and Prof François Duhoux, medical oncologist at the Cliniques Universitaires Saint-Luc in Brussels emphasized that this marks an important milestone in breast cancer management, confirming a sustained and clinically meaningful benefit in a population characterized by high-risk features, such as the presence of more than three positive lymph nodes or one to three nodes with additional adverse factors.

In the intention-to-treat population, the absolute difference in overall survival at 72 months was 1.3%, projected to approach 2% at 84 months. Although seemingly small, Prof Neven underscores that this gain reflects the incremental nature of progress in endocrine-responsive breast cancer, where decades of therapeutic refinement have led to gradual but significant improvements. Notably, fewer patients treated with abemaciclib developed metastatic disease. The proportion of patients who either relapsed with distant metastases or died was reduced from 20% in the control arm to 14% in the abemaciclib arm—representing a relative risk reduction of approximately 30%. This reduction in metastatic events likely predicts a further deepening of the OS benefit over time and suggests a durable carryover effect even after discontinuation of the drug. Also the previously reported benefit in invasive disease-free survival (iDFS) with abemaciclib continues to widen over time, with a 6.5% difference at 7 years (77.4% vs. 70.9%; HR[95%CI]: 0.734[0.657-0.820]; p< 0.0001). 

The OS results of MonarchE also raise important considerations for future therapeutic decisions, particularly regarding patient selection. While the benefit of abemaciclib now unequivocal in this very high-risk populations, the role of ribociclib and other agents in patients with ‘lower high-risk features’ remains to be fully defined. In any case, physicians will have to balance efficacy with potential toxicity, drug–drug interactions, and patient preference in a process shared decision-making.

Importantly, Belgium’s early reimbursement of abemaciclib before the OS data were available has enabled broad real-world experience. Ongoing prospective registries initiated by the Belgian Society of Medical Oncology (BSMO) aim to characterize treatment patterns, resistance mechanisms, and post-relapse therapies.