Verzenio Plus Endocrine Therapy Improves Outcomes HR-Positive, HER2-Negative Breast Cancer

Verzenio plus endocrine therapy improved outcomes for patients with HR-positive, HER2-negative breast cancer, according to research.

Two years of Verzenio (abemaciclib) plus endocrine therapy (ET) in some patients with breast cancer continued to reduce the risk for invasive disease- (IDFS) and distant relapse-free survival (DRFS), according to findings from a recent trial.

Specifically, patients with hormone receptor (HR)-positive, HER2-negative, node-positive, high-risk early breast cancer had reduced risk for IDFS and DRFS when they received the treatment combination of Verzenio and ET for two years.

Verzenio is a type of cancer drug that blocks specific proteins that could prevent cancer cells from growing, according to National Cancer Institute.

These respective findings were determined by five-year efficacy results from a prespecified overall survival (OS, length of time from diagnosis or start of treatment when patients remain alive) interim analysis from the monarchE 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.

The purpose of the phase 3, randomized monarchE trial was to evaluate whether Verzenio plus ET after intial treatment improved IDFS and DRFS among 5,637 patients with hormone receptor-positive, HER2-negative node-positive, high-risk, early breast cancer.

Patients were randomized evenly to receive standard-of-care endocrine therapy of the doctor’s choice for up to 10 years, either with or without the oral Verzenio for two years.

The trial’s researchers separated patients into two cohorts:

• Cohort one: patients with ≥4 positive axillary lymph nodes or one to three positive axillary lymph nodes with at least grade 3 disease and/or tumor size of ≥5 centimeters.
• Cohort two: patients with one to three or more positive axillary lymph nodes, grade 3 disease and tumor size of ≥5 centimeters.

The benefit seen in the intent-to-treat (ITT) population (participants from both cohorts) was consistent with that seen in cohort one.

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 one was observed, for both IDFS and DRFS.

Harbeck established that cohort two data remained immature.

Sustained Benefit

In the third interim analysis, researchers noted that the median follow-up was 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 ITT population, IDFS benefit with the addition of Verzenio to ET was sustained, with 407 events occurring in the investigative arm versus 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 (neoadjuvant vs. adjuvant), 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 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 (208), compared with placebo (234).

“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 news 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.”

Safety

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 (lower amounts of neutrophils, a type of white blood cell) and fatigue, with the most common grade 3 to 4 side effects being neutropenia, leucopenia (lower amounts of white blood cells) and diarrhea.

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

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

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

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