Sustained Abemaciclib Benefit in High-Risk Breast Cancer: MonarchE Trial Update

Joyce O'Shaughnessy, MD, Texas Oncology and Baylor Scott & White Health, discusses findings from the phase 3 monarchE trial (NCT03155997) presented at the 2025 ESMO Congress.

The monarchE trial is of critical importance because it focuses on a highly vulnerable patient group: those with hormone receptor-positive, HER2-negative, node-positive early breast cancer at a very high risk of recurrence. For this specific population, even with the current standard of care, best available endocrine therapy (ET), the risk of the cancer returning and eventually leading to death is unacceptably high. Historical data indicates that approximately one-third of these high-risk patients will unfortunately experience a recurrence and ultimately succumb to their disease while on standard ET alone. This grim prognosis highlights a significant, unmet clinical need for more effective adjuvant treatments.

The development of the CDK4/6 inhibitors, specifically abemaciclib (Verzenio), was prompted by this need, with the goal of introducing them into the curative adjuvant setting to prevent early recurrence. The monarchE trial provided a 2-year course of abemaciclib in combination with standard ET vs ET alone. The community is now benefiting from longer-term follow-up data, which is crucial for assessing the permanent impact of this finite treatment course.

With the median follow-up now exceeding 6 years, and importantly, approximately 75% of the patients having been off the 2-year abemaciclib treatment for at least 4 years, researchers are gaining a true measure of the treatment's sustained benefit. The primary end point of the trial, invasive disease-free survival (IDFS), continues to hold up over this prolonged period. The sustained separation of the Kaplan-Meier curves beyond the treatment period indicates a permanent, or "carryover" effect, meaning the initial benefit of reduced recurrence risk does not simply erode once the drug is stopped. This finding is highly significant, as there had been prior concern, based on data from other trials, that the benefit might only be a delay in recurrence, suggesting that patients would simply recur later. Thankfully, the long-term monarchE results suggest this is not the case.

While the overall survival (OS) benefit, though statistically significantly improved, remains modest in absolute terms at the 6-year mark, the real impact is seen in the reduction of metastatic recurrence. The data shows a approximately 30% reduction in the number of patients developing metastatic disease with the addition of abemaciclib. This disparity is profoundly important because virtually all patients who progress to metastatic breast cancer, regardless of their initial treatment arm, will eventually die from the disease, typically after a median survival of around 5 years following metastasis. The significant reduction in the number of patients developing these incurable metastatic events strongly suggests that the magnitude of the OS benefit is likely to grow larger over the coming years, as the patients in the control arm who developed metastases begin to succumb to their disease. This growing discrepancy in metastatic recurrence will translate into an ever-widening survival gap over time.

Watch more with Dr O'Shaughnessy here.