Abemaciclib With Endocrine Therapy Receives Expanded Approval for Early Breast Cancer

Breast cancer cells.

The FDA has granted approval to abemaciclib (Verzenio®, Eli Lilly and Company) with endocrine therapy—tamoxifen or an aromatase inhibitor—for treatment of adult patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-positive early breast cancer that is at a high risk of recurrence. Patients considered at high risk for recurrence include those with four or more pathologic axillary lymph nodes (pALN) or one to three pALN plus either a grade 3 tumor or a tumor size ≥50 mm. Abemaciclib had previously been granted approval in this setting with an additional requirement of having a Ki-67 score ≥20%, which is no longer required for this indication.

“Abemaciclib is an oral, continuously dosed cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with endocrine therapy for the treatment of HR-positive, HER2-negative advanced breast cancer on the basis of significant improvements in progression-free survival (PFS) and overall survival in combination with fulvestrant and in PFS in combination with nonsteroidal aromatase inhibitors,” reported Stephen Johnston, MD, Head of Medical Oncology at the Royal Marsden NHS Foundation Trust in London, and colleagues, in their published results of the monarchE trial (NCT03155997), on which approval was based. “As such, exploration of the combination of abemaciclib with endocrine therapy is warranted in the adjuvant setting.”

Safety and efficacy were evaluated in the phase 3, open-label, two-cohort trial, in which patients were randomized 1:1 to receive either 150 mg of abemaciclib orally, twice daily, in addition to standard endocrine therapy consisting of tamoxifen or an aromatase inhibitor, or standard endocrine therapy alone. Cohort 1 required patients to have either four or more pALN or one to three pALN and either a grade 3 tumor or a tumor size ≥50 mm. Cohort 2 included those who did not qualify for Cohort 1 and were required to have one to three pALN and tumor Ki-67 score ≥20%.

The primary end point measured was invasive disease–free survival (IDFS). At a median follow-up of 42 months, a statistically significant difference was seen in the intent-to-treat population, which mainly included patients within Cohort 1. At 48 months, IDFS was 85.5% in those receiving abemaciclib and endocrine therapy, compared with 78.6% in those receiving endocrine therapy alone. While data regarding overall survival is not yet mature, more deaths occurred in Cohort 2 in the abemaciclib plus endocrine therapy group compared with those receiving endocrine therapy alone. As a result, the indication is limited to the patient population represented in Cohort 1.

The most common adverse events in ≥20% of patients were diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache.

“The benefit is sustained beyond the completion of treatment with an absolute increase at four years, further supporting the use of abemaciclib in patients with high-risk HR-positive, HER2-negative early breast cancer,” concluded Dr. Johnston and colleagues. “Further follow-up is needed to establish whether overall survival can be improved with abemaciclib plus endocrine therapy in these patients.”

The recommended dosage is 150 mg abemaciclib orally, twice daily, with tamoxifen or an aromatase inhibitor until completion of two years of treatment or until disease recurrence or unacceptable toxicity.

For More Information

Johnston S, Harbeck N, Hegg R, et al (2020). Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2–, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol, 38(34):3987-3998. DOI:10.1200/JCO.20.02514

Johnston S, Toi M, O’Shaughnessy J, et al (2023). Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet, 24(1):77-90. DOI:10.1016/S1470-2045(22)00694-5

Clinicaltrials.gov (2022). Endocrine therapy with or without abemaciclib (ly2835219) following surgery in participants with breast cancer (monarchE). NLM identifier: NCT03155997.

Verzenio® (abemaciclib) prescribing information (2023). Eli Lilly and Company. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/208716s010s011lbl.pdf

US Food and Drug Administration (2023). FDA expands early breast cancer indication for abemaciclib with endocrine therapy. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-early-breast-cancer-indication-abemaciclib-endocrine-therapy 

Image credit: National Cancer Institute.

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