Editor’s Note: At the 2025 ESMO Annual Congress, the overall survival (OS) data from the monarchE trial were released, showing that abemaciclib combined with endocrine therapy significantly improved survival in patients with HR+/HER2- high-risk early breast cancer, reducing the risk of death by 15.8%. This marks the first OS-positive result for a CDK4/6 inhibitor in the adjuvant setting for early breast cancer—representing a major milestone in treatment strategy for high-risk patients. Oncology Frontier invited Professor Li Huiping from Peking University Cancer Hospital to provide an in-depth interpretation of the data, share insights on identifying high-risk patients, and discuss the clinical value of early intervention, offering important guidance for clinical practice.
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Oncology Frontier: At this year’s ESMO Congress, the monarchE study presented its OS results, showing that in patients with HR+/HER2- high-risk early breast cancer, adjuvant abemaciclib plus endocrine therapy significantly improved overall survival compared to endocrine therapy alone (HR 0.84, P = 0.027). What is the clinical significance of this result for adjuvant therapy in early breast cancer?
Prof. Li Huiping: The publication of the OS data from the monarchE study at this meeting is highly significant for the adjuvant treatment of HR+/HER2- early breast cancer, particularly in high-risk populations.
We know that patients with high-risk features—such as those with 1–3 positive axillary lymph nodes accompanied by other risk factors, or ≥4 positive lymph nodes—face a greater risk of early recurrence. Treating high- and low-risk patients identically often leads to different outcomes, which is why treatment intensification is essential for those at high risk.
The monarchE trial was specifically designed for this group of node-positive, high-risk, early breast cancer patients, evaluating adjuvant therapy with a CDK4/6 inhibitor. The trial included two cohorts:
- Cohort 1: ≥4 positive axillary lymph nodes, or 1–3 positive nodes plus at least one high-risk feature (tumor ≥5 cm, or histologic grade 3).
- Cohort 2: 1–3 positive axillary nodes with a Ki-67 index ≥20%.
Patients were randomized 1:1 to receive either abemaciclib (150 mg twice daily) plus standard adjuvant endocrine therapy, or endocrine therapy alone, for a total treatment duration of two years. The primary endpoint was invasive disease-free survival (IDFS), with secondary endpoints including IDFS in the high Ki-67 subgroup, distant relapse-free survival (DRFS), overall survival (OS), safety, pharmacokinetics (PK), and patient-reported outcomes (PROs).
By the data cutoff on July 15, 2025, with a median follow-up of 76 months (6.3 years) and 5,637 patients enrolled, abemaciclib plus endocrine therapy reduced the risk of death by 15.8% compared with endocrine therapy alone (OS 86.8% vs 85.0%; HR 0.842; 95% CI: 0.722–0.981; P = 0.0273).
Additionally, this analysis showed a 26.6% reduction in IDFS risk (nominal P < 0.0001) and a 25.4% reduction in DRFS risk (nominal P < 0.0001).
In summary, for HR+ high-risk early breast cancer patients, endocrine therapy alone is no longer sufficient to control recurrence risk. Combining a CDK4/6 inhibitor such as abemaciclib provides substantial additional benefit. This is the key conclusion of the monarchE trial and signifies a meaningful improvement in survival for this population—an advance of major clinical importance.
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Oncology Frontier: The monarchE trial enrolled high-risk patients (e.g., those with ≥4 positive lymph nodes or 1–3 nodes plus other high-risk features). In your clinical practice, how do you identify patients who truly require intensified adjuvant therapy? Beyond clinicopathologic features, do you also consider genomic assays or biomarkers such as Ki-67?
Prof. Li Huiping: In my view, identifying high-risk patients should be approached from two main perspectives.
From an anatomical standpoint, patients presenting with large primary tumors (≥5 cm) or lymph node involvement, particularly ≥4 positive nodes, are considered high risk.
From a biological or molecular perspective, even if the tumor is small, a high Ki-67 index (≥20%) or high histologic grade (grade 3) indicates aggressive disease and elevated risk.
Breast cancer is no longer regarded as a single disease but rather as a collection of molecular subtypes that guide treatment decisions. In the future, genomic profiling may become further integrated into risk assessment, though it was not included in the monarchE study.
In monarchE, high-risk status was primarily defined by tumor size, nodal status, Ki-67 index, and grade. Since Ki-67 reflects proliferative activity, higher values are associated with increased malignancy, rapid growth, and higher metastatic potential.
For patients with such high-risk features, standard endocrine therapy alone is insufficient. The monarchE study showed that in this population, adding abemaciclib significantly improved IDFS and, notably, achieved an OS benefit after seven years of follow-up. This is a rare and meaningful finding in the adjuvant setting for early breast cancer and underscores the value of intensified adjuvant therapy for high-risk patients.
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Oncology Frontier: In the monarchE trial, 52% of patients in the control group received a CDK4/6 inhibitor upon recurrence, compared to only 34% in the abemaciclib group. Does this suggest that early use of CDK4/6 inhibitors in the adjuvant setting may offer greater survival benefits? How do you balance the concepts of “early intervention” versus “later rescue” in terms of efficacy and accessibility?
Prof. Li Huiping: Based on the monarchE trial alone, we cannot conclusively state that early intervention is superior to later-line treatment. However, from a broader oncologic perspective, disease-free survival and survival with disease are fundamentally different conditions.
Early intervention allows patients to remain disease-free, providing not only a survival advantage but also better quality of life and psychological well-being. In contrast, once recurrence or metastasis occurs, even with subsequent therapy, the treatment journey and life experience change entirely.
The monarchE trial’s true importance lies in showing that adding abemaciclib to standard endocrine therapy for high-risk patients yields significant survival benefits, especially in prolonging disease-free survival. Even though over half of the control arm patients later received CDK4/6 inhibitors, the abemaciclib group still demonstrated an absolute OS benefit of 1.8% (86.8% vs 85.0%) at seven years—a meaningful result that reinforces the importance of early intervention in high-risk patients.
Professor Li Huiping Director, Department of Breast Oncology Peking University Cancer Hospital
