Benefit of adjuvant abemaciclib continues to deepen at longer follow-up

With additional follow-up, the benefit of adjuvant abemaciclib for patients with HR-positive/HER2-negative, node-positive, high-risk early breast cancer continues to deepen in magnitude after completion of treatment, results from the monarchE study showed.

Adjuvant therapy with the CDK4/6 inhibitor abemaciclib combined with endocrine therapy demonstrated significant improvement in invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS) in high-risk, HR-positive/HER2-negative, node-positive early breast cancer after 2 years of follow-up [1,2]. To evaluate the efficacy of abemaciclib after completion of the therapy, an analysis was completed 2 years after the primary outcome analysis. Prof. Stephen Johnston (The Royal Marsden NHS Foundation Trust, UK) presented the results of this analysis [3,4].

The phase 3 monarchE trial (NCT03155997) enrolled 5,637 patients who were 1:1 randomised to receive abemaciclib for 2 years plus endocrine therapy (≥5 years) or endocrine therapy alone. All patients were high-risk based on either clinical pathological features (Cohort 1, n=5120) or on the Ki-67 test (Cohort 2, n=517). After a median follow-up of 42 months, IDFS curves between the 2 treatment arms continued to widen in favour of abemaciclib. The absolute benefit of abemaciclib in IDFS 4-year rate was 6.4% compared with 2.8% after 2 years and 4.8% after 3 years of follow-up. HR for IDFS improved from 0.782 in the first year of follow-up to 0.602 after 4 years of follow-up.

Likewise, DRFS benefit of abemaciclib persisted beyond completion of abemaciclib: The absolute benefit of abemaciclib in DRFS 4-year rate was 5.9% compared with 2.5% after 2 years and 4.1% after 3 years of follow-up. HR for DRFS improved from 0.725 in the first year of follow-up to 0.581 after 4 years of follow-up. Addition of abemaciclib to endocrine therapy did improve IDFS and DFRS both in Cohort 1 and Cohort 2. Ki-67 score showed to be prognostic for a poor outcome, but not predictive of abemaciclib efficacy. Although the overall survival data are not yet mature, there was a numerical difference in deaths (157 vs 173) and number of patients with metastatic disease (125 vs 249) in favour of the abemaciclib arm.

“These data further support the addition of adjuvant abemaciclib to endocrine therapy for patients with HR-positive/HER2-negative, node-positive, high-risk early breast cancer,” concluded Prof. Johnston.

1. Johnston SRD, et al. J Clin Oncol. 2020;38:3987–3998.
2. Harbeck N, et al. Ann Oncol. 2021;32:1571–1581.
3. Johnston SRD, et al. Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: results from a pre-planned monarchE overall survival interim analysis, including 4-year efficacy outcomes. Abstract GS1-09, SABCS 2022, 6–10 December, San Antonio, TX, USA.
4. Johnston SRD, et al. Lancet Oncol. 2023;24(1):77–90.

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Posted on 1 February 2023