Verzenio, Endocrine Therapy Boosts Outcomes in High-Risk Breast Cancer

Patients with hormone receptor-positive, HER2-negative high-risk early breast cancer with disease in their lymph nodes experienced continued invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) by adding Verzenio (abemaciclib) to endocrine therapy (ET), according to results from the monarchE clinical trial.

“The data are consistent with a carryover effect and further support the addition of adjuvant (Verzenio) to ET for patients with HR-positive, HER2-negative, node-positive, high-risk early breast cancer,” Dr. Nadia Harbeck, director of the Breast Center, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Munich, Ludwig Maximilians University Hospital, Munich, Germany, said of the five-year follow-up presented at ESMO Congress 2023.

Sustained Benefit

In the third interim analysis, the data cutoff was July 3, 2023, at a median follow-up of 54 months.

“At the critical five-year landmark, all patients are now off (Verzenio), and I think it’s noteworthy that more than 80% of the patients have been followed for at least two years,” Harbeck said.

In the intent-to-treat (ITT) population, IDFS benefit, which is the amount of time patients lived without invasive disease, with the addition of Verzenio to ET was sustained, with 407 events occurring in the investigative arm vs 585 with ET alone, reducing the risk for invasive disease by 32%. The five-year IDFS rates were 83.6% and 76.0%, respectively.

IDFS benefit from Verzenio was consistent across subgroups.

“(This was) independent of age; menopausal status; the type of setting of chemotherapy given (pre- or post-surgical]; the number of positive lymph nodes; and I think is also very important, the endocrine agent combined with (Verzenio). In this study tamoxifen as well as the aromatase inhibitor could be used,” Harbeck added.

Similarly, in the ITT population, DRFS, which is the time patients live without experiencing relapse in other parts of the body, benefit continued with the addition of Verzenio, with 345 events vs 501 with ET alone, reducing the risk for distant relapse by 32.5%. Five-year DRFS rates were 86.0% and 79.2%, respectively.

Lastly, OS was still immature; however, there were fewer deaths reported in the Verzenio arm, compared with placebo (208 vs 234, respectively).

“The mature recurrence efficacy benefit demonstrated in monarchE, achieved with a two-year treatment duration, reinforce Verzenio as the standard of care in this curative setting, where Verzenio is the only CDK4/6 inhibitor approved to treat people with HR-positive, HER2-negative, node-positive, high risk early breast cancer,” Dr. David Hyman, chief medical officer, Lilly, said in a press release. “Reaching the five-year outcomes benchmark with adjuvant Verzenio should provide further confidence for those patients where treatment intensification is needed to help them achieve their goal of remaining cancer-free.”

Further Benefit Among Cohorts

The investigators separated patients into two cohorts:

  • Cohort 1: patients with four or more positive axillary lymph nodes or one to three positive axillary lymph nodes with at least grade 3 disease and/or tumor size of 5 cm or larger
  • Cohort 2: patients with one to three or more positive axillary lymph nodes, central Ki67 20% or more, grade 3 disease and tumor size of 5 cm or larger

The benefit seen in the population treated with Verzenio was consistent with that seen in cohort 1.

Among those treated with Verzenio, the risk for invasive disease was reduced by 33%. The five-year IDFS rates in the Verzenio and ET-alone groups were 83.2% and 75.3%, respectively.

Similarly, DRFS benefit continued with the addition of Verzenio, compared with ET alone, reducing the risk for distant relapse by 33.5%. The five-year DRFS rates were 85.6% and 78.5%, respectively.

For those treated with Verzenio plus ET vs placebo, these treatment effects in cohort 1 were observed, regardless of Ki-67 Index, which indicates how rapidly cells are dividing, for both IDFS ; five-year rates, 81.0vs 72.0%, respectively and DRFS; five-year rates, 83.4% vs 75.2%, respectively.

Harbeck noted that cohort 2 data remained immature.


No new safety signals were identified and Harbeck noted the safety results were similar to the previous analyses.

The most frequent side effects associated with Verzenio included diarrhea, neutropenia (decrease in a type of white blood cells) and fatigue, with the most common grade 3 to 4 side effects being neutropenia, leucopenia (decrease in leukocytes) and diarrhea.

Among those treated with Verzenio, vs those who were not, more patients experienced one or more treatment-emergent adverse events (98.4% v 88.9%, respectively), at least 1 or more grade 3 or higher side effect (50.0% v 16.9%) and one or more serious side effect (15.6% v 9.2%).

However, Harbeck noted that serious side effects, regardless of causality, reported for patients in the five-year, long-term follow-up were higher in the ET-alone arm (7.3%), compared with those treated with Verzenio plus ET (6.5%).

monarchE Trial

In the open-label, randomized, phase 3 trial, investigators aimed to evaluate if adjuvant Verzenio plus ET improved IDFS and DRFS among 5637 patients with hormone receptor-positive, HER2-negative node-positive, high-risk, early breast cancer. Patients were randomly assigned to receive standard-of-care endocrine therapy of physician’s choice for up to 10 years, either with or without 150 mg Verzenio orally twice a day for two years.

“monarchE is the only adjuvant CDK4/6 inhibitor trial designed exclusively for patients with high-risk disease,” Harbeck explained. “…A goal of optimal adjuvant therapy is to eradicate micrometastatic disease within an achievable treatment period in order to maximize treatment adherence. Abemaciclib induces a potent and sustained apoptotic effect and is dosed continuously, in contrast with other CDK4/6 inhibitors that are administered intermittently and induce senescence.”

To be eligible, patients had to be 18 years of age or older, have hormone receptor-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence, and an ECOG performance status of 0 or 1, indicating that they can perform their daily tasks with little or no assistance.

Patients were stratified for prior chemotherapy, menopausal status and region.

IDFS served as the primary end point, while secondary end points included IDFS in high Ki67 populations, DRFS, overall survival (OS; time from treatment until death from any cause) safety, how the drug moves throughout the body and patient-reported outcomes.

In a previously reported interim analysis published in The Lancet Oncology, IDFS was not reached in either group. The four-year IDFS rate with the addition of Verzenio was 85.8%, compared with 79.4% in those who received ET alone.

During the four-year follow-up, two treatment-related deaths had occurred in the Verzenio plus ET group, vs none in the ET-alone group.

“Continued follow-up is ongoing until final assessment of OS,” Harbeck concluded.

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