Data from phase III monarchE trial of adjuvant Verzenio plus ET showing deepening benefit in early breast cancer published in The Lancet Oncology
Eli Lilly announced updated results from the pivotal Phase III monarchE trial of adjuvant Verzenio (abemaciclib) in combination with standard 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)
Data include updated results from a prespecified analysis reflecting a median follow-up of 3.5 years, with all patients having now discontinued or completed the two-year Verzenio treatment period. The absolute increase in invasive disease-free survival (IDFS) and distance relapse-free survival (DRFS) continued to deepen in magnitude at four years, to 6.4% and 5.9%, respectively, reflecting improvements from the two- and three-year rates. This IDFS and DRFS benefit was seen across all prespecified subgroups, regardless of Ki-67 score. While overall survival (OS) data remain immature at this time, fewer deaths were observed in the Verzenio-plus-ET arm compared to the ET monotherapy arm (HR=0.929, 95% CI: 0.748, 1.153).
At the July 1, 2022 data cutoff, in the ITT population, the risk of developing invasive disease was reduced by 33.6% (HR=0.664, 95% CI: 0.578, 0.762; nominal p<0.0001). the four-year idfs rate was 85.8% for patients treated with verzenio plus et compared to 79.4% for patients treated with et alone, reflecting an absolute difference of 6.4% (compared to 2.8% at two years). the majority of the idfs events were distant metastatic disease. adjuvant verzenio also reduced the risk of developing metastatic disease by 34.1% (hr="0.659," 95% ci: 0.567, 0.767; nominal p><0.0001). the four-year drfs rate was 88.4% for patients treated with verzenio plus et compared to 82.5% for patients treated with et alone, an absolute difference of 5.9% (compared to 2.5% at two years). consistent with the findings of previous analyses, a high ki-67 score correlated with increased risk of recurrence, but idfs and drfs results showed a similar benefit regardless of ki-67 status. data presented at sabcs also included efficacy outcomes in the fda-approved population, as well as the cohort 1 population.
OS data remain immature. Fewer deaths were observed in the Verzenio-plus-ET arm (157 [5.6%] of 2,808 patients) compared to the ET monotherapy arm (173 [6.1%] of 2,829 patients) (HR=0.929, 95% CI: 0.748, 1.153; p = 0.50). Fewer deaths due to breast cancer occurred in the Verzenio-plus-ET arm compared to the ET alone arm (117 [4.2%] of 2,791 patients vs. 138 [4.9%] of 2,800 patients). Nearly twice as many patients in the control arm have developed and are living with metastatic disease compared to those receiving Verzenio. Continued follow-up is ongoing until final assessment of OS.
The most frequent adverse events (AEs) were diarrhea, neutropenia, and fatigue in the Verzenio arm, and arthralgia, hot flush, and fatigue in the control arm; the most common Grade 3-4 AEs were neutropenia, leucopenia, and diarrhea in the Verzenio arm and arthralgia, neutropenia, and ALT increased in the ET alone arm. These data, which include results for investigational uses in the intent-to-treat (ITT) and Cohort 1 populations, were presented as an oral presentation at the 2022 San Antonio Breast Cancer Symposium (SABCS) and simultaneously published in The Lancet Oncology.
See: "Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial" Prof Stephen R D Johnston et al. The Lancet Oncology December 06 2022 DOI:https://doi.org/10.1016/S1470-2045(22)00694-5
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