Benzinga | Oct 14, 2021 01:34PM EDT

Eli Lilly & Co Updates Verzenio Phase 3 MonarchE Trial Data Presented At ESMO Virtual Plenary And Simultaneously Published In Annals Of Oncology

Eli Lilly and Company (NYSE:LLY) today announced updated data from the positive Phase 3 monarchE trial evaluating the investigational use of Verzenio(r) (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 oftime 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 (<20%) or high (?20%) Ki-67 score among patients with high-risk clinical and pathological features (Table 2 below). 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.

"The results from monarchE are truly impressive and we are encouraged by the consistency of the treatment benefit and increasing magnitude of effect observed over time in reducing the risk of recurrence and development of metastatic disease," said Joyce A. O'Shaughnessy, M.D., Celebrating Women Chair in Breast Cancer Research, Baylor University Medical Center, Texas Oncology, US Oncology, Dallas Texas, monarchE investigator and presenter at today's ESMO Virtual Plenary. "These data suggest that the addition of adjuvant Verzenio to endocrine therapy in the high risk early breast cancer setting has the potential to change the way we treat these patients and may address a significant unmet need for those with clinical and pathological risk features who are in need of new treatment options."

The following table shows the evolution of IDFS and DRFS data in the ITT population.

Table 1.

Primary Outcome1 Additional Follow-Up Data cut-off date July 8, 2020 April 1, 2021

Patients off study 41.0% 89.6%treatment period

Efficacy Results Verzenio + ET alone Verzenio + ET alone ET ET

Median follow-up, months 19.1 27.1

Invasive disease-free survival (IDFS)

Events, n 163 232 232 333

IDFS rates, % (95% CI) 2-year 92.3 (90.9, 89.3 (87.7, 92.7 (91.6, 90.0 (88.8, 93.5) 90.7) 93.6) 91.1)

3-year Not Not 88.8 (87.0, 83.4 (81.3, estimable estimable 90.3) 85.3)

HR (95% CI) 0.71 (0.58, 0.87) 0.70 (0.59, 0.82)

p-value &#x2A;Nominal p-value = &#x2A;Nominal p-value 0.0009 <0.0001

Distant relapse-free survival (DRFS)

Events, n 131 193 191 278

DRFS rates, % (95% CI) 2-year 93.8 (92.6, 90.8 (89.3, 94.1 (93.2, 91.6 (90.5, 94.9) 92.1) 95.0) 92.6)

3-year Not Not 90.3 (88.6, 86.1 (84.2, estimable estimable 91.8) 87.9)

HR (95% CI) 0.69 (0.55, 0.86) 0.69 (0.57, 0.83)

1 Johnston SRD, Harbeck N, Hegg R, et al; monarchE Committee Members andInvestigators. Abemaciclib combined with endocrine therapy for the adjuvanttreatment of HR+, HER2-, node-positive, high-risk, early breast cancer(monarchE) [published online ahead of print, September 20, 2020]. J ClinOncol. doi:10.1200/JCO.20.02514.

&#x2A;The primary efficacy endpoint was statistically significant at interimanalysis 2

The following table shows IDFS in Cohort 1 according to centrally determined Ki-67 score [low (<20%), high (?20%)].&#x2A;

Table 2.

Verzenio + ETET aloneHR (95% CI)

Cohort 1 Ki-67 High, N = 2003

Patients, N 1017 986 0.626 Events, n 104 158 (0.488, 0.803)3-Year IDFS Rates86.1% 79.0%

Cohort 1 Ki-67 Low, N = 1914

Patients, N 946 968 0.704 Events, n 62 86 (0.506, 0.979)3-Year IDFS Rates91.7% 87.2%

&#x2A;Data from Additional Follow-up analysis with a data cut-off date of April1, 2021

"We are extremely pleased with the consistency of the landmark results from monarchE and are excited to see these important data shared with the breast cancer community," said David Hyman, M.D., chief medical officer, oncology at Lilly. "Verzenio treatment benefit observed at the primary outcome analysis was maintained with 27 months of median follow-up, including beyond the Verzenio treatment period, reinforcing our confidence in the observed treatment effect."

Adverse reactions from monarchE were consistent with the known safety profile for Verzenio.1 A higher incidence of Grade ?3 adverse events (AEs) and serious adverse events was observed with Verzenio plus ET compared to ET alone (50% vs. 16% and 15% vs. 9%, respectively). The most frequent AEs were diarrhea, neutropenia, and fatigue in the Verzenio plus ET arm, and arthralgia, hot flush, and fatigue in the ET alone arm.