Abemaciclib combined with adjuvant endocrine therapy in patients with high risk early breast cancer who received neoadjuvant chemotherapy (NAC).
Authors: Martin Miguel , Hegg Roberto , Kim Sung-Bae , Schenker Michael , Grecea Daniela , García-Sáenz José A. , Papazisis Konstantinos , Ouyang Quchang , Lacko Aleksandra , Oksuzoglu Berna , Reeves James Andrew , Okera Meena , Testa Laura , Shimizu Chikako , Wei Ran , Forrester Tammy D , Munoz Maria , Zimmermann Annamaria H. , Headley Desiree , Johnston Stephen R. D. 
Published: June 2021

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Background: monarchE, a phase 3, open-label, randomized study evaluating abemaciclib combined with adjuvant endocrine therapy (ET) compared to ET alone in patients with HR+, HER2-, high risk early breast cancer (EBC), resulted in a statistically significant improvement in invasive disease-free survival (IDFS) (HR = 0.713; 95% CI: 0.583, 0.871). NAC is used in patients with HR+, HER2- EBC at higher risk of recurrence despite often limited response, suggesting a need for enhanced adjuvant ET. Methods: Patients with ≥4 positive notes (LNS), or 1-3 LNS and either Grade 3 disease, tumor size ≥5 cm, or central Ki-67 ≥20% were eligible. Prior chemotherapy (NAC, adjuvant, none) was one of the stratifications factors. Prior therapy and tumor characteristics prior to study entry were collected. Here, we present the results of the prespecified subgroup of patients who received NAC. Results: Out of 5,637 randomized patients, 2056 (36.5%) received NAC. For 84.8%, the chosen regimen included anthracycline + cyclophosphamide + taxane, for 4.4%, it included anthracycline + taxane. A total of 1044 (50.8%) patients who received NAC had a radiologic tumor size between 2-5 cm and 599 (29.1%) had tumors ≥5 cm at diagnosis. 6.2%, 49.4% and 36.7% of patients had tumors with histologic Grade 1, 2, 3 respectively. 55.2% of patients had LNS ≥4+ and 44.4% had 1-3+ LNS. Central Ki-67 prior to NAC was ≥20% in 64.8% of patients with available Ki-67 results (664 (32.3%) patients had missing Ki-67 results). Evaluation of clinical and pathological measures of response will be presented. A multivariate cox regression analysis of IDFS in the intent-to-treat (ITT) population, identified prior chemotherapy as prognostic, suggesting patients who received NAC were at risk of a worse outcome. Primary outcome efficacy data for patients who received NAC are shown in the table below. Abemaciclib + ET demonstrated treatment benefit in terms of IDFS vs ET alone (HR: 0.614 95% CI: 0.473, 0.797) with 2-year IDFS rates of 87.2% vs 80.6%, respectively. The addition of abemaciclib to ET resulted in an improvement in distant relapse-free survival (DRFS) (HR: 0.609, 95% CI: 0.459, 0.809), with 2-year DRFS rates of 89.5% and 82.8%, respectively. Safety profile was similar to the overall safety population. Conclusions: Patients with HR+, HER2- EBC who received NAC were noted to be at a higher risk of recurrence. In this subgroup, abemaciclib combined with ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS, which was numerically greater than in the ITT population. Safety data were consistent with abemaciclib safety profile. Clinical trial information: NCT03155997. [Table: see text]