FDA Expands Abemaciclib Indication in HR+/HER2–, Node+, High-Risk Breast Cancer


The FDA approved an expanded indication for abemaciclib (Verzenio) in combination with endocrine therapy for the adjuvant treatment of adult patients with hormone receptor (HR)–positive, HER2-negative, node-positive, early breast cancer that is at a high risk of recurrence.

This article originally appeared on OncLive®.

The FDA approved an expanded indication for abemaciclib (Verzenio) in combination with endocrine therapy for the adjuvant treatment of adult patients with hormone receptor (HR)–positive, HER2-negative, node-positive, early breast cancer that is at a high risk of recurrence.1

Now, those determined to be high risk who are eligible to receive the agent can be identified based on nodal status, tumor size, and tumor grade. This expanded indication removes the Ki-67 score requirement for patient selection.

Hands holding pink breast cancer ribbons

Hands holding pink breast cancer ribbons

The label expansion decision is based on 4-year findings from the phase 3 monarchE trial (NCT03155997) in which adjuvant abemaciclib plus endocrine therapy (n = 2555) resulted in an invasive disease-free survival (iDFS) benefit beyond the 2-year treatment course vs endocrine therapy alone (n = 2565). Notably, over time. the absolute difference was found to increase between the treatment arms.

Data indicated that at 4 years, 85.5% of patients who received abemaciclib plus endocrine therapy continued to be free of recurrence vs 78.6% of those given endocrine therapy alone; this translated to an absolute difference in iDFS of 6.9%. At 2 years, the absolute difference rate between the arms was 3.1%; this rate at 3 years was 5.0%. Abemaciclib plus endocrine therapy resulted in a 35% reduction in the risk of recurrence vs endocrine therapy alone (HR, 0.653; 95% CI, 0.567-0.753).

No new safety signals were observed, and the overall safety data were noted to be consistent with what has previously been reported with the agent.

"Our goal in intensifying treatment for early breast cancer is to maintain remission and prevent the recurrence of cancer. The magnitude of benefit seen in the 4-year data from the monarchE study reinforces my confidence in adjuvant Verzenio as the standard-of-care for high risk patients in this setting," Erika P. Hamilton, MD, medical oncologist, director of Breast and Gynecologic Cancer Research at Sarah Cannon Research Institute, and an investigator on the monarchE clinical trial, stated in a press release. "The initial Verzenio FDA approval in early breast cancer was practice-changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them."

The open-label, randomized, phase 3 trial enrolled adult patients with HR-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence who were at least 18 years of age and had an Eastern Cooperative Oncology Group performance status of 0 or 1.2

Those in cohort 1 had to have tumor involvement in at least 4 axillary lymph nodes (pALN) or involvement in 1 to 3 pALN and at least 1 of the following: tumor grade 3 or tumor size of at least 50 mm. Those in cohort 2 could not be eligible for cohort 1; they had to have 1 to 3 pALN and a Ki-67 score of at least 20%.

Study participants were randomly assigned 1:1 to receive 2 years of oral abemaciclib at 150 mg twice daily plus physician's choice of standard endocrine therapy in the form of tamoxifen or an aromatase inhibitor or endocrine therapy alone.

Stratification factors include previous treatment received (neoadjuvant chemotherapy vs adjuvant chemotherapy vs no chemotherapy), menopausal status (premenopausal vs postmenopausal), and region (North America/Europe vs Asia vs other). At the end of the treatment period on the study, standard adjuvant endocrine therapy was continued for at least 5 years if determined to be appropriate.

iDFS served as a major efficacy outcome measure. Overall survival was another key outcome measure.

A total of 5637 patients were enrolled into 2 cohorts; 91% (n = 5120) were enrolled to cohort 1. The median age was 51 years (range, 22-89). Most patients were women (99%) and White (70%). A little more than half (53%) of patients were premenopausal. Regarding prior chemotherapy, 37% received neoadjuvant treatment and 59% received adjuvant treatment. Ninety-six percent of patients previously received radiotherapy.

Additionally, 65% of patients had 4 or more positive lymph nodes, with 22% having at least 10 positive lymph nodes, 41% had grade 3 tumor, and 24% had pathological tumor size of at least 50 mm. Moreover, 99% of patients had estrogen receptor–positive disease and 87% had progesterone receptor positivity. Initial endocrine therapy comprised letrozole (39%), tamoxifen (31%), anastrozole (22%), or exemestane (8%).

Abemaciclib is now approved for use in the full cohort 1 population which accounted for 91% of the study population. The significant improvement in iDFS was observed with abemaciclib plus endocrine therapy vs endocrine therapy alone in the intention-to-treat population, mostly due to the patients in cohort 1.

Although the data in cohort 2 continue to be immature, more deaths were observed in the investigative arm vs the control arm (n = 10/253 vs n = 5/264).

The median duration of exposure to abemaciclib was 24 months.

Sixty-two percent of patients required dose interruptions due to toxicity, and 44% required dose reductions. Toxicities resulted in treatment discontinuation for 19% of patients. Moreover, 0.8% of patients who received abemaciclib plus endocrine therapy experienced fatal toxicities.

The most frequent toxicities included diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache. The most common grade 3 or 4 toxicities were neutropenia, leukopenia, diarrhea, and lymphopenia.

"This expanded approval will allow us to bring Verzenio to many more women and men with hormone receptor–positive, HER2-negative, high-risk early breast cancer in the curative setting – before patients experience recurrence, potentially to incurable metastatic disease," Jacob Van Naarden, chief executive officer of Loxo@Lilly, added in a press release. "The initial adjuvant approval for Verzenio changed the treatment paradigm, and the strength of the monarchE results supporting this approval underscores the role this differentiated CDK4/6 inhibitor can play in reducing the risk of recurrence in early breast cancer."

The FDA has also broadened the indicated use of abemaciclib when used in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer. This updated indication now includes all adult patients, with the expanded indication including pre-/perimenopausal women when paired with ovarian suppression.


  1. US FDA broadens indication for Verzenio (abemaciclib) in HR+, HER2-, node-positive, high risk early breast cancer. News release. Eli Lilly and Company. March 3, 2023. Accessed March 3, 2023.
  2. Abemaciclib (Verzenio). Prescribing information. Eli Lilly and Company. Revised March 2023. Accessed March 3, 2023.
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