Episode 15: 5-Year Follow-Up of Abemaciclib Plus Endocrine Therapy in High-Risk HR+/HER2- Early Breast Cancer – Insights from the MonarchE Study

In this episode of WND Breast, Dr Kevin Punie of GZA Hospitals and Prof Evandro de Azambuja from Institut Jules Bordet focus on the advantages of adjuvant CDK4/6 inhibitors for patients at high risk of recurrence from HR+/HER2- breast cancer.

The pioneering MonarchE trial demonstrated the benefit of incorporating abemaciclib alongside endocrine therapy in early-stage breast cancer patients facing a high relapse risk in the adjuvant setting. Patients with HR+/HER2- disease remain susceptible to relapse, despite 5, 7 or even 10 years of endocrine therapy. The strategy of integrating CDK4/6 inhibitors aims to mitigate this risk, inspired by its success in the metastatic setting.

In this phase 3 trial involving around 5,600 patients, endocrine therapy alone for 2 years versus endocrine therapy combined with abemaciclib was compared. Initial results indicated improvements in both IDFS and DRFS. At ESMO2023, updated data with a median follow-up of 54 months demonstrated sustained enhancements with continued abemaciclib treatment. The significant divergence of survival curves between the two treatment arms highlights the absolute benefits of 7.6% in IDFS and 6.7% in DRFS favouring abemaciclib, reinforcing its effectiveness in preventing relapse. Additional analysis highlights the significance of abemaciclib in preventing the onset of metastatic disease.

Data on OS remain inconclusive, necessitating prolonged observation to identify benefits in this patient cohort. While preliminary indications hint at a favourable OS trend and reduced mortality in the abemaciclib arm, it is premature to draw definitive conclusions. The anticipated side effects observed in the metastatic setting are manageable and can require dose adjustments to ensure treatment continuity.

Abemaciclib treatment has gained approval from both Belgian regulatory authorities and the EMA, rendering it accessible to eligible patients with HR+/HER2- disease at high risk of relapse. The criteria defining high-risk disease encompass either ≥4 positive axillary lymph nodes, or 1-3 positive axillary lymph nodes coupled with either grade 3 disease or a tumour size >5 cm, instilling confidence in the decision to offer this treatment to eligible patients.

While awaiting OS data, the evolving survival curves indicate a growing number of patients achieving cure over time, consolidating the current standard of care. Experts are navigating patient selection criteria, primarily based on tumour stage and grade. They question the best approach when genomic testing suggests a low-risk gene expression profile in patients with N1 disease. In such scenarios, while genomic testing aids in chemotherapy decision-making, it does not prognosticate the potential benefits of abemaciclib in this subset of patients. Given this limitation, if a patient meets the eligibility criteria, proceeding with adjuvant abemaciclib therapy is recommended.