Survival Data Strengthens Case for Abemaciclib in High-Risk Breast Cancer

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.

Watch the first part of the interview with Dr O'Shaughnessy here.

For most patients, the data already available from the monarchE trial regarding the prevention of recurrence is sufficient to warrant taking abemaciclib. The speaker emphasizes that these are very high-risk patients. However, there is a fraction of patients for whom knowing that their chances of dying of breast cancer are now statistically significantly reduced might make a difference in their decision-making. The expectation is that the survival benefit will become more pronounced over time.

Global Access and Clinical Discussion

While the speaker doesn't have many patients who would deliberate over this, they suggest that for other parts of the world, needing to see survival data from a regulatory or payer standpoint could be critical. The hope is that this new data will lead to more access for patients globally.

In the U.S., the speaker believes the survival data makes the discussion between doctors and patients even more compelling. Physicians can now stress that their responsibility includes ensuring patients have access to all medications that reduce the risk of dying from the disease. This adds a layer of urgency and necessity to the clinical conversation.

Addressing Resistance and Future Research

The speaker highlights the crucial need to understand the resistance mechanisms that allow cancer to recur despite treatment. While celebrating the trial's success, the speaker notes that recurrences and deaths still occur even with abemaciclib.

Future research should focus on molecular analyses and the disclosure of data, such as from circulating tumor DNA drawn at the time of recurrence. The goal is to identify the genomic alterations and mutations that allow the cancer to persist, even in patients who have received chemotherapy, endocrine therapy, and two years of abemaciclib. Understanding "why" these recurrences happen is essential for fashioning the next set of trials to target these resistance mutations. The underlying question is always, "How can we do better?"

Optimizing Treatment Safety and Access

The speaker points out that significant progress has been made in safely administering the medication and reducing toxicities. Specifically, they note that dose reductions do not decrease the benefit of the drug; this is a clear finding. If a patient's quality of life is suffering due to side effects like diarrhea, a dose reduction can effectively manage the problem while still providing the full therapeutic benefit.

Furthermore, the speaker believes that the access problem has been largely addressed in the U.S. for the vast majority of patients. For those without sufficient prescription coverage or high copays, there is a copay assistance program available.

Full Clinical Implementation

Despite these advancements, the full implementation of the treatment for all eligible patients in clinical practice remains an ongoing issue. The speaker notes that these are long upfront discussions with patients, who are often managing a sequence of treatments including chemotherapy, surgery, radiation therapy, and anti-estrogen therapy. Since abemaciclib does not start until after radiation therapy, there's a need to ensure continuity of care and that patients cycle back to initiate the drug. The hope is that the positive survival data will make the case even more compelling for the full implementation of the treatment for all patients who meet the monarchE trial's eligibility criteria.