Adjuvant Verzenio in combination with endocrine therapy (ET) continued to demonstrate a significant improvement in reducing the risk of recurrence in patients with HR+ HER2-, node-positive, high risk early breast cancer

With additional follow up, the treatment benefit of Verzenio plus ET was maintained over time and extended beyond the two-year treatment period; mature safety analysis was also consistent with previous results

Consistent Verzenio treatment benefit in reducing risk of recurrence observed in patients regardless of Ki-67 score

INDIANAPOLIS, Oct. 14, 2021 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced updated data from the positive Phase 3 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). These data were presented at today's ESMO Virtual Plenary and simultaneously published in the Annals of Oncology.

As previously published in the Journal of Clinical Oncology,1 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 ≥4 positive axillary lymph nodes (ALN), or 1-3 positive ALN and either Grade 3 disease or tumor size ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALN and centrally determined Ki-67 score of ≥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 today's 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 (Table 1 below). 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 ≥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 (