Lilly Announces Updated Data from the Verzenio® (abemaciclib) Phase 3 monarchE Trial Presented at SABCS and Simultaneously Published in The Lancet Oncology

Lilly Announces Updated Data from the Verzenio® (abemaciclib) Phase 3 monarchE Trial Presented at SABCS and Simultaneously Published in The Lancet Oncology

The benefit of adjuvant Verzenio in combination with endocrine therapy continues to deepen with additional follow-up, now demonstrating an absolute improvement in invasive disease-free survival (IDFS) and distance relapse-free survival (DRFS) rates of 6.4% and 5.9% at four years, respectively, in patients with HR+, HER2-, node-positive, high risk early breast cancer

INDIANAPOLIS, Dec. 6, 2022 /PRNewswire/ — Eli Lilly and Company (NYSE: LLY) today announced updated results from the pivotal Phase 3 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). These data, which include results for investigational uses in the intent-to-treat (ITT) and Cohort 1 populations, were presented today as an oral presentation at the 2022 San Antonio Breast Cancer Symposium (SABCS) and simultaneously published in The Lancet Oncology.

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). There were no new safety findings, and overall results are consistent with the well-established safety profile for Verzenio.

“These results from the monarchE trial provide further evidence of the clinically meaningful benefit that adjuvant Verzenio adds to standard endocrine therapy in patients with high risk early breast cancer, a population with an urgent need to intensify therapy. Moreover, this benefit continues to deepen at four years, well beyond the two-year treatment course with adjuvant Verzenio,” said Stephen Johnston, M.D., Ph.D., Professor of Breast Cancer Medicine and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust (London, U.K.) and lead investigator for the monarchE trial.

The monarchE trial (N=5,637) included women and men with HR+, HER2-, node-positive EBC with a high risk of disease recurrence. The ITT population included patients enrolled to both Cohort 1 and Cohort 2, with Cohort 1 (N=5,120) representing 91% of all enrolled patients. Cohort 1 enrolled patients based on high risk clinical pathological factors (≥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.

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.

“The continued strengthening of the adjuvant Verzenio benefit seen at four years further underscores the potential importance of these data for women and men with HR+, HER2-, node-positive, high risk early breast cancer,” said David Hyman, M.D., chief medical officer, Loxo@Lilly. “We are pleased with these results and have submitted an application with the FDA to expand our adjuvant indication in the U.S. based on these data.” 

As previously published in the Journal of Clinical Oncology,1 and subsequently updated in the Annals of Oncology,2 monarchE met its primary endpoint of a statistically significant improvement in IDFS in the 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. On October 12, 2021, the FDA approved Verzenio in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with HR+, HER2-, node-positive, early breast cancer at high risk of recurrence and a Ki-67 score of ≥20% as determined by an FDA-approved test.3

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