LBA17 Adjuvant abemaciclib plus endocrine therapy for HR+, HER2-, high-risk early breast cancer: Results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes

Two years (yrs) of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-yr treatment (tx) period in patients (pts) with hormone receptor positive, human epidermal growth factor receptor 2 negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-yr efficacy results from a prespecified overall survival (OS) interim analysis. Pts were randomized (1:1) to receive ET for at least 5 yrs +/- abemaciclib for 2 yrs (tx period). High-risk EBC was defined as either ≥4 positive axillary lymph nodes (ALN) or 1-3 ALN with Grade 3 disease and/or tumor ≥5 cm (Cohort 1). A smaller group of pts were enrolled with 1-3+ ALN and central Ki67 ≥20% (Cohort 2). The intent-to-treat (ITT) population consisted of Cohort 1 (5120 pts) and Cohort 2 (517 pts). OS in the ITT population was tested for statistical significance in the gated strategy. Hazard ratios (HR) were estimated using Cox proportional hazard model. In the ITT population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with a HR of 0.680 (95% CI: 0.599, 0.772) for IDFS and 0.675 (95% CI: 0.588, 0.774) for DRFS. This persistence of abemaciclib benefit translated to continued separation of the KM curves resulting in a 5-yr absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with IDFS/DRFS rates of 6.0%/5.3% at 4 yrs and 4.8%/4.1% at 3 yrs. Tx benefit in Cohort 1 was consistent with ITT. No new safety signals were observed. There continued to be fewer deaths in the abemaciclib plus ET arm compared to the ET arm (208 vs 234; HR 0.903; p=0.284); significance was not met. At the pivotal 5-yr mark for adjuvant EBC trials, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence well beyond the completion of tx. The increasing absolute improvement at 5 yrs is consistent with a carryover effect and further supports the use of abemaciclib in pts with high-risk EBC. OS data are evolving in favor of abemaciclib arm, and follow-up continues.