Two years of adjuvant abemaciclib combined with endocrine therapy (ET) improved invasive disease-free survival (IDFS) compared with ET alone in patients with hormone receptor (HR)-positive/HER2-negative, node-positive, high-risk early breast cancer. Previous analysis showed that in patients who received neoadjuvant chemotherapy (NAC), abemaciclib plus ET demonstrated sustained IDFS improvement. Although high baseline Ki-67 was associated with worse prognosis in the intent-to-treat population, the benefit of abemaciclib was observed regardless of Ki-67 index. This study evaluates the prognostic and predictive value of baseline pre- and post-NAC Ki-67 index, as well as changes in Ki-67 following NAC.
Ki-67 index was determined centrally for patients receiving NAC. Subgroups were categorized based on Ki-67 index pre-NAC (high ≥20%; low <20%), post-NAC, and changes in Ki-67 following NAC. Efficacy outcomes were assessed using a Cox proportional-hazards regression model.
Among 5637 patients enrolled in monarchE (NCT03155997) at the data cutoff date of July 3, 2023, 2057 (36.5%) received NAC. Ki-67 index pre-NAC was available for 1359 patients (high, n=879; low, n=480), and post-NAC Ki-67 results were available for 579 patients (high, n=118; low, n=461). Baseline characteristics and demographics were balanced across treatment arms and subgroups. Four-year IDFS rates comparing abemaciclib with ET indicated that patients with high Ki-67 index pre-NAC (hazard ratio, 0.63; 95% confidence interval [CI], 0.49-0.82) and post-NAC (hazard ratio, 0.53; 95% CI, 0.31-0.90) had a higher risk of recurrence compared with low Ki-67 (pre-NAC; hazard ratio, 0.59; 95% CI, 0.40-0.89, and post-NAC; hazard ratio, 0.45; 95% CI, 0.28-0.72), but the abemaciclib treatment benefit was consistent regardless of Ki-67 status. All patients showed a benefit from the addition of abemaciclib regardless of their change in Ki-67 post-NAC: Ki-67 high to low (hazard ratio, 0.35; 95% CI, 0.19-0.64), Ki-67 remains high (hazard ratio, 0.63; 95% CI, 0.36-1.10), and Ki-67 remains low (hazard ratio, 0.71; 95% CI, 0.33-1.50). NAC effectively reduced Ki-67 index from high to low in approximately 75% of tumors classified as high Ki-67 pre-NAC. However, patients whose tumors retained a high Ki-67 index following NAC had the highest risk of recurrence. Importantly, the treatment benefit with abemaciclib plus ET versus ET alone was consistent across all subgroups, regardless of Ki-67 index or changes in Ki-67 following NAC.
Ki-67 index, both pre- and post-NAC, as well as changes in Ki-67 following NAC, were prognostic markers for patient outcomes. The monarchE trial demonstrated that the addition of abemaciclib to ET improved outcomes across all Ki-67 subgroups, highlighting the broad efficacy of abemaciclib in this high-risk patient population.
Source: Martin M, Johnston SR, Harbeck N, et al. MonarchE: evaluation of prognostic and predictive value of Ki-67 index pre and post neoadjuvant chemotherapy (NAC) and changes following NAC. Presented at: ESMO Congress 2025. October 19, 2025; Berlin, Germany. Abstract 295MO.