Benefit of Adjuvant Abemaciclib in High-Risk Early Breast Cancer Is Sustained at 5 Years

A preplanned interim analysis of the monarchE (NCT03155997) trial, with a median follow-up of 54 months, confirmed sustained invasive disease–free survival (IDFS) and distant relapse-free survival (DRFS) benefits for the addition of abemaciclib (Verzenio; Lilly USA) to standard endocrine therapy (ET) in high-risk early breast cancer (EBC), according to a presentation at the European Society for Medical Oncology Congress 2023 in Madrid, Spain, on October 20, 2023.¹ Abemaciclib was approved by the FDA in 2021 for adjuvant treatment of high-risk EBC based on a 36-month IDFS benefit demonstrated in the monarchE trial.²

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MonarchE was an open-label, phase 3 trial that randomized patients with hormone receptor–positive, HER2- negative, high-risk EBC to receive abemaciclib for 2 years plus standard ET or ET alone.2 Patients included in the trial had completed surgery and, as indicated, radiotherapy and/or adjuvant/neoadjuvant chemotherapy. Patients with 4 or more positive lymph nodes (LN) or 1 to 3 positive LNs and either tumor size of 5 cm or more, histologic grade 3, or central Ki-67 at 20% or more were eligible. The primary end point of the trial was IDFS, with secondary end points including DRFS, overall survival, and safety.

At the time of the updated analysis, all patients completed treatment with abemaciclib and more than 80% of patients had 2 or more years of follow-up post completion of abemaciclib therapy. The 5-year IDFS was 83.6% in the abemaciclib plus ET arm compared with 76% in the ET alone arm (HR, 0.68; 95% CI, 0.599-0.772; P < .001), representing an absolute IDFS difference of 7.6% at 5 years. For DRFS, the abemaciclib plus ET arm had a 5-year DRFS rate of 86%, whereas the ET alone arm had a rate of 79.2% (HR, 0.675; 95% CI, 0.588-0.774; P < .001), demonstrating a 6.7% difference in DRFS rate at 5 years.

Furthermore, although the overall survival data remain immature, fewer deaths have occurred within the abemaciclib plus ET arm compared with the ET alone arm (208 vs 234, respectively). The safety analysis also remained consistent with prior analyses, and no new safety signals were reported with longer follow-up.

A secondary exploratory analysis was performed that demonstrated consistent abemaciclib treatment effect regardless of Ki-67, estrogen receptor, or progesterone receptor expression level.³ The consistency of the treatment effect indicates that these biomarkers alone should not be used to select patients for adjuvant abemaciclib use. Currently, abemaciclib is the only CDK4/6 inhibitor that is FDA approved for the adjuvant treatment of high-risk EBC, and longer follow-up confirms a sustained benefit well beyond the 2-year treatment period.

Ribociclib (Kisqali; Novartis) in combination with a nonsteroidal aromatase inhibitor (NSAI) has also been shown to improve IDFS compared with NSAI alone for high-risk EBC, based on interim analysis results of the phase 3 NATALEE trial (NCT03701334), which were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.⁴ At the time of data presentation at ASCO, only 20.2% of patients had completed adjuvant ribociclib therapy. To date, ribociclib is not FDA approved for adjuvant treatment of EBC.

References

1. Harbeck N. 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 out comes. Presented at: European Society for Medical Oncology Congress 2023; October 20-24, 2023; Madrid, Spain.

2. Johnston SRD, Harbeck N, Hegg R, et al; monarchE Committee Members and Investigators. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38(34):3987-3998. doi:10.1200/JCO.20.02514

3. Goetz M. Prognostic and predictive impact of estrogen/progesterone receptor (ER/PR), and Ki-67 expression: an exploratory analysis from the monarchE trial in patients with high-risk, HR+, HER2-, early breast cancer (EBC). Presented at: European Society for Medical Oncology Congress 2023; October 20-24, 2023; Madrid, Spain.

4. Slamon DJ, Stroyakovskiy D, Yardley DA, et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: primary results from the phase III NATALEE trial. J Clin Oncol. 2023;41(suppl 17):LBA500. doi:10.1200/JCO.2023.41.17_suppl.LBA500

About the Author

Colleen Bohnenkamp, PharmD, BCOP, BCPS, is an oncology clinical pharmacist at the University of Kansas Health System.