Role of Ki-67

The researchers also evaluated the role of the Ki-67 as a biomarker. Ki-67 was tested centrally from all suitable untreated breast primary tumor samples — representing around 80% of study participants — using the IHC MIB-1 pharmDx (Dako Omnis) assay.

Overall, abemaciclib provided an IDFS benefit in patients with a high Ki-67 index (HR, 0.663; 95% CI, 0.524-0.839; P =.0006). The 3-year IDFS rate was 86.8% with abemaciclib and 80.8% with ET alone.

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In cohort 1, the absolute IDFS benefit at 3 years was significantly higher in patients with a high Ki-67 index, suggesting that Ki-67 has prognostic value in this patient population.

“However, treatment benefit was observed in both cohort 1 [Ki-67] high and low populations, indicating benefit from abemaciclib regardless of Ki-67 index,” Dr O’Shaughnessy said.

She added that, although the clinical utility of Ki-67 has been challenged by high variability in results, data have demonstrated high reproducibility with the assay employed in monarchE.5,6

Safety Results

The updated safety data were consistent with the known safety profile of abemaciclib, Dr O’Shaughnessy noted.

The rate of grade 3 or higher adverse events (AEs) was higher with abemaciclib than with ET alone — 50% and 16%, respectively. The rate of serious AEs was also higher with abemaciclib than with ET alone — 15% and 9%, respectively.

The most frequent AEs in the abemaciclib arm were diarrhea, neutropenia, and fatigue. The most frequent AEs in the ET-alone arm were arthralgia, hot flush, and fatigue.

Next Steps

This study raises several important questions, according to Dr Bardia. For instance, it’s unclear why the monarchE results differ from results of trials testing another CDK4/6 inhibitor, palbociclib. Both the PALLAS and PENELOPE-B trials ( Identifiers: NCT02513394; NCT01864746) showed no significant benefits with the addition of palbociclib to ET.

Other considerations include the optimal treatment duration, whether all eligible patients should receive abemaciclib given the AE risks and financial costs, and whether further suitable patients can be identified using other biomarkers.

Furthermore, it’s unknown how long the benefits of abemaciclib will persist, Dr Bardia said. He asked, “Does abemaciclib just delay the onset of metastatic disease, or can it actually prevent metastatic disease?”

To answer that, researchers will continue to follow patients enrolled on monarchE.

“Additional analyses will be performed as planned until the final overall survival analysis,” Dr O’Shaughnessy said.

Disclosures: This research was supported by Eli Lilly and Company. Some ESMO Plenary presenters declared affiliations with biotech, pharmaceutical, and/or device companies. Please refer to the original presentation and the published study for a list of disclosures.


  1. O’Shaughnessy J. Adjuvant abemaciclib combined with endocrine therapy (ET): Updated results from monarchE. Presented at: ESMO Virtual Plenary. October 14-15, 2021.
  2. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. Published online October 14, 2021. doi:10.1016/j.annonc.2021.09.015
  3. US Food and Drug Administration. FDA approves abemaciclib with endocrine therapy for early breast cancer. Media Release. Published October 13, 2021. Accessed November 2, 2021.
  4. Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38:3987-3998. doi:10.1200/JCO.20.02514
  5. Polley MYC, Leung SCY, McShane LM, et al. An international Ki67 reproducibility study. J Natl Cancer Inst. 2013;105 (24):1897-1906. doi:10.1093/jnci/djt306
  6. Nielsen G, Gu Y, Weaver A, et al. Development of a novel clinical trial immunohistochemistry (IHC) assay using Ki-67, clone MIB-1, monoclonal antibody for Dako Omnis. Virchows Arch. 2020;477(Suppl 1):1-390. doi:10.1007/s00428-020-02938-x