Background
Two years of adjuvant abemaciclib plus endocrine therapy (ET) improved invasive disease-free survival (iDFS) over ET alone in patients with hormone receptor–positive/HER2-negative (HER2–), node-positive, high-risk disease. In patients who received neoadjuvant chemotherapy (NAC), abemaciclib plus ET showed sustained invasive disease-free survival (iDFS) improvement (HR, 0.65; 95% CI, 0.54-0.73; 4-year iDFS rates: 81% abemaciclib plus ET vs 72% ET alone, Δ9%). In the intent-to-treat population, while high baseline Ki-67 was associated with worse prognosis, benefit was observed with abemaciclib regardless of Ki-67 index. Here, we evaluate the prognostic and predictive value of baseline (pre-) and post-NAC Ki-67 index and of the changes in Ki-67 following NAC.
Methods
Ki67 was determined centrally. In patients receiving NAC,
Ki-67 index pre- or post-NAC was assessed in subgroups by Ki-67 index (high ≥ 20%; low < 20%) and by changes of Ki-67 index following NAC.
Results
Overall, 2057/5637 (36.5%) of patients received NAC. Ki67 index pre-NAC was available for 1359 patients (high, n = 879; low, n = 480) and of these, 579 patients had Ki67 index post-NAC (high, n = 118; low, n = 461). Four-year iDFS rates indicate patients with high Ki67 pre- and post-NAC have higher risk of recurrence (pre-NAC: HR, 0.63; 95%CI, 0.49-0.82 in high Ki-67 and HR, 0.59; 95% CI, 0.40-0.89 in low Ki-67; post-NAC: HR, 0.53; 95% CI, 0.31-0.90 in high Ki-67 and HR, 0.45; 95% CI, 0.28-0.72 in low Ki-67); Ki-67 pre- to post-NAC: Ki-67 remained high (HR, 0.63; 95% CI, 0.36-1.10), Ki-67 remained low (HR, 0.71; 95% CI, 0.33-1.50), and changed from high to low (HR, 0.35; 95% CI, 0.19-0.64). Among patients who had both pre- and post-NAC Ki-67 results available, NAC reduced the Ki-67 index to low in approximately 75% of high Ki-67 tumors. Patients whose tumors retained a high Ki-67 index following NAC had the highest risk of recurrence. Treatment benefit of abemaciclib plus ET vs ET alone was consistent across subgroups regardless of Ki-67 index or changes in Ki-67.
Conclusions
Ki-67 index pre- or post-NAC and changes in Ki-67 following NAC were prognostic of patients outcomes, but not predictive of abemaciclib treatment benefit in monarchE as benefit with abemaciclib in addition to ET was observed across all groups.
Previously presented at ESMO 2025.
Study is sponsored by Eli Lilly and Company.
