Phase III monarchE trial of Verzenio in breast cancer published in Annals of Oncology – Eli Lilly

Eli Lilly announced updated data from the positive Phase III monarchE trial evaluating the investigational use of Verzenio (abemaciclib) in combination with standard adjuvant endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, high risk early breast cancer (EBC). As previously published in the Journal of Clinical Oncology, monarchE met its primary endpoint of a statistically significant improvement in invasive disease-free survival (IDFS) in the intent-to-treat (ITT) population for patients treated with adjuvant Verzenio plus ET compared to those treated with ET alone. Consistent with expert guidelines, IDFS was defined as the length of time before breast cancer comes back, any new cancer develops, or death.

The trial included women and men with HR+ HER2-, node-positive EBC who had a high risk of disease recurrence based on clinical and pathological features (N=5,637). Patients were assigned to one of two cohorts. Cohort 1 enrolled patients with at least 4 positive axillary lymph nodes (ALN), or 1-3 positive ALN and either Grade 3 disease or tumor size of at least 5 cm. Cohort 2 enrolled patients with 1-3 positive ALN and centrally determined Ki-67 score of at least 20% (defined in the study as “Ki-67 high”). Ki-67 is a marker of cellular proliferation. Ki-67 score was also determined centrally in Cohort 1 patients with a suitable sample, but Ki-67 determination was not required for enrollment in this cohort. The ITT population included both Cohort 1 and Cohort 2. Data in the latest presentation and publication include updated results reflecting median follow-up of 27 months. In the updated analysis, the benefit of Verzenio on IDFS and distant relapse-free survival (DRFS) was maintained. At three years, the absolute improvement rates in IDFS and DRFS were 5.4% and 4.2%, respectively.

Exploratory piecewise analyses of the IDFS and DRFS hazard ratio (HR) estimates within each year were also conducted, which demonstrated increasing magnitude of IDFS effect size over time: from the first year (0-1yr HR = 0.80, 95% CI: 0.59, 1.03) to the second year (1-2yr HR = 0.68, 95% CI: 0.52, 0.87), and strengthened beyond the two-year study treatment period (2+yr HR = 0.60, 95% CI: 0.40, 0.86). Similarly, the DRFS HR estimates strengthened from the first year (0-1yr HR = 0.73, 95% CI: 0.52, 0.99) to the second year (1-2yr HR = 0.68, 95% CI: 0.51, 0.88), and persisted beyond the two-year study treatment period (2+yr HR = 0.69, 95% CI: 0.45, 1.03). The impact of Ki-67 score on prognosis and likelihood of benefit from Verzenio was also analyzed. As expected, a high Ki-67 score of at least 20% was prognostic of increased recurrence risk among patients with high-risk clinical and pathological features. However, Verzenio conferred consistent benefit in reducing risk of recurrence regardless of having a low (<20%) or high (at least 20%) Ki-67 score among patients with high-risk clinical and pathological features.

With 90 percent of patients now having completed the two-year treatment period or discontinued early, safety data are considered mature and remain consistent with the known profile of Verzenio. All patients in monarchE will continue to be followed to assess overall survival and other endpoints. Overall survival data were not yet mature. These data were presented at ESMO Virtual Plenary and simultaneously published in the Annals of Oncology.

See: “Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study”
N. Harbeck et al. Annals of Oncology Published:October 14, 2021 DOI:https://doi.org/10.1016/j.annonc.2021.09.015