Abemaciclib in Combination with Endocrine Therapy for Adjuvant Treatment of Hormone Receptor-Positive, HER2-Negative, Node-Positive Early Breast Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Giovany Orozco Leal, Nigel Armstrong, Ashleigh Kernohan, Charlotte Ahmadu, Diarmuid Coughlan, Kevin McDermott, Steven Duffy, Susan O'Meara, Tomos Robinson, Luke Vale, Jos Kleijnen

Research output: Contribution to journalReview articlepeer-review


The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Eli Lilly) of abemaciclib (Verzenios) to submit evidence for the clinical and cost effectiveness of this drug in combination with endocrine therapy (ET) for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence, as part of the Institute's Single Technology Appraisal (STA) process. Kleijnen Systematic Reviews Ltd, in combination with Newcastle University, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarised the Company Submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The ERG produced a critical review of the evidence for the clinical and cost-effectiveness evidence in the CS and also independently searched for relevant evidence and modified the manufacturer decision analytic model to examine the impact of altering some of the key assumptions. A systematic literature review identified the MonarchE trial, an ongoing, open-label, randomised, double blind trial involving 5637 people comparing abemaciclib in combination with ET versus ET alone. The trial included two cohorts that used different inclusion criteria to define high risk of recurrence. The ERG considered Cohort 1 as an adequate representation of this population and the AC concluded that Cohort 1 was generalisable to National Health Service clinical practice. Trial results showed improvements in invasive disease-free survival for the abemaciclib arm, which was considered an appropriate surrogate outcome. The ERG believed that the modelling structure presented in the de novo economic model by the company was appropriate but highlighted several areas of uncertainty that had the potential to have a significant impact on the resulting incremental cost-effectiveness ratio (ICER). Areas of uncertainty included the extrapolation of long-term survival curves, the duration of treatment effect and treatment waning, and the proportion of patients who receive other CDK4/6 treatments for metastatic disease after receiving abemaciclib. ICER estimates were £9164 per quality-adjusted life-year gained for the company's base-case and £17,810 for the ERG's base-case. NICE recommended abemaciclib with ET as an option for the adjuvant treatment of HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence.

Original languageEnglish
Pages (from-to)741-750
Number of pages10
Issue number7
Early online date23 Mar 2023
Publication statusPublished - 1 Jul 2023

Bibliographical note

Funding Information:
This project was commissioned by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (NIHR135447). See the HTA programme website for further project information ( https://www.nihr.ac.uk/explore-nihr/funding-programmes/health-technology-assessment.htm ). This summary of the ERG report was compiled after NICE issued the FAD. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of NICE or the Department of Health.

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.


  • Adult
  • Humans
  • Female
  • Breast Neoplasms/drug therapy
  • State Medicine
  • Aminopyridines
  • Benzimidazoles
  • Adjuvants, Immunologic
  • Cost-Benefit Analysis
  • Technology Assessment, Biomedical/methods
  • Quality-Adjusted Life Years
  • Randomized Controlled Trials as Topic

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