Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-year treatment period in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-year efficacy results from a prespecified overall survival (OS) interim analysis. In the intent-to-treat population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with hazard ratios of 0.680 (95% CI, 0.599 to 0.772) for IDFS and 0.675 (95% CI, 0.588 to 0.774) for DRFS. This persistence of abemaciclib benefit translated to continuous separation of the curves with a deepening in 5-year absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with rates of 6% and 5.3% at 4 years and 4.8% and 4.1% at 3 years. With fewer deaths in the abemaciclib plus ET arm compared with the ET-alone arm (208 v 234), statistical significance was not reached for OS. No new safety signals were observed. In conclusion, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence beyond the completion of treatment. The increasing absolute improvement at 5 years is consistent with a carryover effect and further supports the use of abemaciclib in patients with high-risk EBC.

Trial registration: ClinicalTrials.gov NCT03155997.

FIG 1.

Kaplan-Meier survival curves of (A) IDFS, (B) DRFS, and (C) OS in the intent-to-treat population. The absolute difference might slightly differ from the subtraction between estimated rates because of rounding. DRFS, distant relapse-free survival; ET, endocrine therapy; HR, hazard ratio; IDFS, invasive disease-free survival; OS, overall survival.

FIG 2.

Forest plot of subgroup analyses. Invasive disease-free survival in the ITT prespecified subgroups. ECOG PS, Eastern Cooperative Oncology Group performance status; ET, endocrine therapy; IDFS, invasive disease-free survival; ITT, intention-to-treat; IWRS, Interactive-voice Web Response System.

FIG A1.

CONSORT diagram. ET, endocrine therapy.

FIG A2.

Forest plot of subgroup analyses. Distant relapse-free survival in the ITT prespecified subgroups. DRFS, distant relapse-free survival; ECOG PS, Eastern Cooperative Oncology Group performance status; ET, endocrine therapy; ITT, intention-to-treat; IWRS, Interactive-voice Web Response System.

FIG A3.

Bar plot of survival status over time. Patients in the ITT population who died or had distant metastases. ET, endocrine therapy; IA, interim analysis; ITT, intention-to-treat; OS, overall survival.

FIG A4.

Kaplan-Meier survival curves of (A) IDFS, (B) DRFS, and (C) OS in cohort 1. The absolute difference might slightly differ from the subtraction between estimated rates because of rounding. DRFS, distant relapse-free survival; HR, hazard ratio; IDFS, invasive disease-free survival; OS, overall survival.

FIG A5.

Kaplan-Meier survival curves of (A) IDFS, (B) DRFS, and (C) OS in cohort 1 Ki-67–high subpopulation. The absolute difference might slightly differ from the subtraction between estimated rates because of rounding. DRFS, distant relapse-free survival; HR, hazard ratio; IDFS, invasive disease-free survival; OS, overall survival.