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

• DOI: 10.1200/jco.23.01994
• Publication Date: 2024-01-09T20:59:17Z
• Authors: Priya Rastogi; Joyce O'Shaughnessy; Miguel Martin; Frances Boyle; Javier Cortes; Hope S. Rugo; Matthew P. Goetz; Erika P. Hamilton; Chiun-Sheng Huang; Elzbieta Senkus; Alexey Tryakin; Irfan Cicin; Laura Testa; Patrick Neven; Jens Huober; Zhimin Shao; Ran Wei; Valérie André; Maria Munoz; Belen San Antonio; Ashwin Shahir; Nadia Harbeck; Stephen Johnston
• Keywords: Male; Erbb2 Protein, Human; Adjuvant Chemotherapy; Receptor, ErbB-2; Hormone Receptor-Positive, Her2-Negative Breast Cancer; Benzimidazole Derivative; Aminopyridines; Antineoplastic Agent; Phase 3 Clinical Trial; ErbB-2; Immunologic; Epidermal Growth Factor Receptor 2; Antineoplastic Combined Chemotherapy Protocols; Overall Survival; Receptor, Erbb-2; 600; Breast Tumor; Treatment Outcome; Local; Tumor Recurrence; Female; Cohort Analysis; Receptor; Human; Adult; Gastrointestinal Disease; İnfection; Major Clinical Study; 610; Breast Neoplasms; Follow Up; Article; Drug Withdrawal; Adjuvants, Immunologic; Distant Recurrence Free Survival; Humans; Comparative Study; Adjuvants; Controlled Study; Aged; Cancer Hormone Therapy; Abemaciclib; Tamoxifen; CLINICAL TRIAL UPDATES; Neoplasm Recurrence; Aminopyridine Derivative; Aromatase İnhibitor; Mortality Rate; İmmunological Adjuvant; Drug Efficacy; Benzimidazoles; Neoplasm Recurrence, Local

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.