Benefit From Adjuvant Abemaciclib Plus Endocrine Therapy Sustained Among Patients With HR-Positive, HER2-Negative Breast Cancer

Updated 5-Year Efficacy Results From the Phase 3 MonarchE Trial 

According to updated 5-year efficacy results from the phase 3 monarchE trial, adjuvant abemaciclib plus endocrine therapy continued to reduce the risk of invasive and distant disease recurrence after completion of treatment among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, high-risk early breast cancer.

“Patients with [HR-positive, HER2-negative], node-positive early breast cancer are at high risk of recurrence and need intensification of treatment,” stated Priya Rastogi, MD, The UPMC Hillman Cancer Center, NSABP Foundation, Pittsburgh, Pennsylvania, and coauthors. “Two years of adjuvant abemaciclib in combination with endocrine therapy is an internationally approved standard of care.”

In this global trial, 5637 patients were placed into Cohort 1 if they had at least 4 positive pathologic axillary lymph nodes or 1 to 3 positive pathologic axillary lymph nodes with additional high-risk features of either grade 3 disease or tumor ≥5 cm (n = 5120), or into Cohort 2 if they had the presence of 1 to 3 positive pathologic axillary lymph nodes and central ki-67 ≥20% (n = 517). Patients were then randomized on a 1-to-1 basis to receive at least 5 years of endocrine therapy with or without the addition of abemaciclib. The primary end points included 5-year invasive disease-free survival (IDFS), distant relapse-free survival (DRFS), and overall survival (OS) rates based on Kaplan-Meier methods. 

At a median follow-up of 54 months, 80% of patients had been followed for at least 4 years. There was a sustained benefit of adjuvant abemaciclib in reducing the risk of developing an IDFS event (hazard ratio [HR] 0.680; 95% confidence interval [CI], 0.599 to 0.772; nominal P < .001). Kaplan-Meier curves continued to separate, demonstrating the absolute improvement in IDFS was further deepened at 5 years to 7.6% from 6% at 4 years, 4.8% at 3 years, and 2.8% at 2 years. The addition of abemaciclib also improved DRFS (HR, 0.675; 95% CI, 0.588 to .0774; nominal P < .001). The absolute benefit in DRFS rate increased to 6.7% at 5 years from 5.3% at 4 years, 4.1% at 3 years, and 2.5% at 2 years. 

At that time, 8.6% of patients in the abemaciclib arm and 10.3% of patients in the endocrine therapy arm had either withdrawn from treatment or were lost to follow-up. No new safety signals were identified. There were 208 deaths in the abemaciclib arm, and 234 deaths in the endocrine therapy arm. While fewer deaths occurred in the abemaciclib arm, OS did not reach statistical significance (HR, 0.903; 95% CI, 0.749 to 1.088; P = .284). Serious adverse events regardless of causality continue to be reported among all patients who enter long-term follow-up. In the endocrine therapy arm, 7.3% of patients experienced serious adverse events compared to 6.5% of patients in the abemaciclib arm, due to more infections and gastrointestinal disorders in the endocrine therapy arm. 

“These 5-year outcomes demonstrate strength in the maturity of the monarchE data and provide further assurance of benefit beyond the 2-year treatment period, which is important given two negative trials for the CDK4/6 inhibitor, palbociclib, in [HR-positive, HER2-negative early breast cancer],” concluded Dr Rastogi et al.

Source:

Rastogi P, O’Shaughnessy J, Martin M, et al. 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. J Clin Oncol. Published online: January 9, 2024. doi:10.1200/JCO.23.01994