The oral, twice-daily tablet reduced the risk of long-term breast cancer recurrence by approximately 32%, and at 5 years, improved invasive disease-free survival by 7.6%.
A recent phase 3 trial that evaluated 2 years of treatment with adjuvant abemaciclib (Verzenio; Eli Lilly and Co.) with endocrine therapy (ET) reinforced the combination as the standard of care for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive early breast cancer (EBC) with a high risk of recurrence. The results from the phase 3 monarchE (NCT03155997) trial, which compared the abemaciclib combination vs ET alone, were shared at the 2023 European Society for Medical Oncology (ESMO) Congress. Abemaciclib is approved to treat patients with certain HR+, HER2- breast cancers in the adjuvant and advanced or metastatic setting, and it is the first and only CDK4/6 inhibitor approved to treat patients with node-positive, high risk EBC.
The global, randomized, open-label, multicenter clinical trial enrolled 5637 adults with HR+, HER2-, node-positive EBC at a risk of recurrence, with the primary endpoint of invasive disease-free survival (IDFS). Patients were randomized to receive either 150 mg of abemaciclib twice daily plus standard-of-care (SOC) adjuvant ET (n = 2808), or SOC adjuvant ET alone for 2 years (n = 2829), with ET continuing for at least 5 years if necessary. Patients had a median follow-up of 4.5 years.
"The 5-year time period is an established landmark for adjuvant breast cancer clinical trials and is an important milestone for patients and physicians in this curative setting," said monarchE investigator Nadia Harbeck, MD, PhD, director of the Breast Center and chair for Conservative Oncology, Department of OB&GYN, LMU University Hospital, Munich, Germany and presenter of the results at the 2023 ESMO Congress. "These 5-year monarchE data clearly demonstrate a carryover effect beyond the completion of 2 years of abemaciclib treatment, with the IDFS and [distant relapse-free survival (DRFS)] curves continuing to separate, reinforcing confidence in the role of abemaciclib added to endocrine therapy in the adjuvant setting for those with a high risk of recurrence."
The results indicated that the intent-to-treat population’s risk decreased by 32% (HR=0.680, 95% CI: 0.599, 0.772; nominal p<0.001), with the IDFS and DRFS continuing to deepen in magnitude at 5 years (7.6% and 6.7%, respectively), reflecting improvements from the 2-, 3-, and 4-year rates. Although most of the IDFS events were DRFS events, the DRFS benefit was maintained with abemaciclib in reducing the risk of developing distant recurrence or death by 32.5% (HR=0.675, 95% CI: 0.588, 0.774; nominal p<0.001).
Overall survival data remain immature; however, fewer deaths were presented in the abemaciclib plus ET cohort (208 [7.4%] of 2808 patients) compared to the ET cohort (234 [8.3%] of 2829 patients). Further, almost twice as many patients receiving ET alone (n = 269) had developed and are living with metastatic disease compared to patients who received abemaciclib (n = 138). In addition, there were no new safety findings.
The most common adverse events (AEs) reported among patients in the abemaciclib with ET cohort were diarrhea, neutropenia, and fatigue, whereas the most common AEs in the ET monotherapy cohort were arthralgia, hot flash, and fatigue. Further, the most common Grade 3 to 4 AEs were neutropenia, leucopenia, and diarrhea in the abemaciclib and ET cohort and arthralgia, neutropenia, and ALT increase in the ET cohort.
"The mature recurrence efficacy benefit demonstrated in monarchE, achieved with a 2-year treatment duration, reinforce [abemaciclib] as the standard of care in this curative setting, where [abemaciclib] is the only CDK4/6 inhibitor approved to treat people with HR+, HER2-, node-positive, high risk early breast cancer," said David Hyman, MD, chief medical officer, Lilly. "Reaching the 5-year outcomes benchmark with adjuvant [abemaciclib] should provide further confidence for those patients where treatment intensification is needed to help them achieve their goal of remaining cancer-free."
Eli Lilly and Company. Landmark 5-Year monarchE Outcome Data Demonstrate Verzenio® (abemaciclib)'s Long-Term Impact on Cancer Recurrence in High-Risk Early Breast Cancer. News release. October 20, 2023. Accessed October 20, 2023. https://investor.lilly.com/news-releases/news-release-details/landmark-5-year-monarche-outcome-data-demonstrate-verzenior