IRELAND’S HSE APPROVES LILLY’S ABEMACICLIB IN COMBINATION WITH ENDOCRINE THERAPY FOR ADJUVANT TREATMENT OF PEOPLE WITH HR+, HER2- EARLY BREAST CANCER AT HIGH-RISK OF RECURRENCE

IRELAND’S HSE APPROVES LILLY’S ABEMACICLIB IN COMBINATION WITH ENDOCRINE THERAPY FOR ADJUVANT TREATMENT OF PEOPLE WITH HR+, HER2- EARLY BREAST CANCER AT HIGH-RISK OF RECURRENCE

Abemaciclib in combination with endocrine therapy is the first CDK4/6 inhibitor to be made available in Ireland from 01 June, 2024 following approval for reimbursement from the Health Service Executive (HSE) for people with HR+, HER2-, nodepositive early breast cancer at high-risk of recurrence 1,2

In a Phase 3 trial adjuvant treatment with abemaciclib in combination with endocrine therapy significantly decreased the risk of breast cancer recurrence versus endocrine therapy alone (Primary Endpoint: Invasive Disease-Free Survival) 2

Approximately 20-30% of people with HR+, HER2- Early Breast Cancer may develop incurable metastatic disease.3 The recommendation of abemaciclib as adjuvant treatment will provide a newly reimbursed treatment option for people with breast cancer that have a high risk of recurrence.

Eli Lilly and Company announced today that the Health Service Executive (HSE) has recommended abemaciclib in combination with endocrine therapy, within its marketing authorisation, as an option for adjuvant treatment of hormone receptor-positive, HER2-negative, nodepositive early breast cancer in adults whose disease is at high risk of recurrence, defined as pathological
tumour involvement in:

• at least 4 positive axillary lymph nodes, or
• 1 to 3 positive axillary lymph nodes, and at least one of the following criteria:
  o grade 3 disease (defined as at least 8 points on the modified Bloom-Richardson grading system or equivalent), or
  o primary tumour size of at least 5 cm.

This approval for reimbursement from HSE means that abemaciclib will be available for the first time in Ireland from 01 June, 2024. 1

“This decision / approval establishes abemaciclib as the first CDK4/6 inhibitor to be made available in Ireland for the treatment of HR+, HER2-, high risk early breast cancer,” said Professor Janice Walshe, UCD Clinical Professor & Consultant Medical Oncologist St Vincent’s University Hospital.

“This significant milestone enhances treatment options for eligible patients diagnosed with high risk early breast cancer in Ireland”.

Professor Stephen Johnston, Consultant Medical Oncologist and Head of The Breast Unit at the Royal Marsden NHS Foundation Trust, Professor of Breast Cancer Medicine at the Institute of Cancer Research, London, and Lead Global Principal Investigator for the monarchE trial, said: “It’s a privilege to see the positive results from the monarchE trial, which was an international effort, translate into a treatment option for HR+ and HER2- breast cancer patients in Ireland who have a high risk of their cancer recurring.

Despite previously receiving the optimal standard of care, this high risk node-positive group represents about 13% of early breast cancer patients each year who are at a much higher risk of their disease returning. For them abemaciclib is a significant breakthrough and is the first licensed treatment for this patient group in 20 years. I’m delighted that it will be available through Ireland’s healthcare system for eligible patients to help reduce their risk of recurrence.”

This approval for reimbursement is based on results from the Phase 3 monarchE trial, which met its primary endpoint.

• At the pre-planned interim analysis, statistically significant improvement in invasive disease-free survival (IDFS) was observed with abemaciclib in combination with endocrine therapy (ET) vs ET alone.4
• In a further exploratory analysis 91% of patients in Cohort 1 were off the 2-year study treatment period. Abemaciclib given in combination with ET decreased the risk of breast cancer recurrence by 32 percent compared to standard adjuvant ET alone for people with HR+, HER2-, node-positive early breast cancer at high risk of recurrence (HR: 0.68 [95% CI: 0.57-0.81], p < 0.0001, absolute risk differences between the study groups is 3% at 24 months). Benefit was observed across patient subgroups defined by geographic region, menopausal status and prior chemotherapy within Cohort 1. 2
• Safety data from monarchE were consistent with the known safety profile of abemaciclib and no new safety signals were observed. The clinically relevant adverse events (>10% occurrence and events of interest) were diarrhoea, infections, neutropenia, fatigue, nausea, anaemia, headache, vomiting, stomatitis, thrombocytopenia, decreased appetite, alopecia, ALT and AST increase, rash. Reasons for discontinuations include diarrhoea (5.3%), fatigue (2.0%), and neutropenia (0.9%).5 Many of the discontinuations due to adverse events occurred in the early months of treatment. Other adverse events of interest included venous thromboembolism (2.5%), pulmonary embolism (1%) and interstitial lung disease (3.2%). Most patients who required a dose hold or reduction after an adverse event were able to remain on study treatment.4,6

MonarchE randomised 5,637 patients with HR+, HER2-, high risk EBC from more than 600 sites in 38 countries.4 High risk of recurrence in Cohort 1 was defined by disease characteristics: either ≥4 positive axillary lymph nodes (pALN) or 1-3 pALN and at least one of the following criteria: tumour size ≥5 cm or histologic Grade 3. Among the 5,637 randomised patients, 5,120 were enrolled in Cohort 1, representing 91 % of the ITT population. In Cohort 1, patient demographics and baseline tumour characteristics were balanced between treatment arms. Patients were treated with abemaciclib 150mg twice daily in combination with ET for two years (treatment period) or until meeting criteria for discontinuation. Patients in both arms will receive 5-10 years of ET
as clinically indicated (2 years on study followed by a further 3-8 years in long-term follow-up). 6

For complete information about this medicine’s benefits and risks please consult the summary of product characteristics.

About Early Breast Cancer

Breast cancer is the most common cancer among women worldwide.7 Although the prognosis for HR+, HER2- early breast cancer is generally positive, 20-30 percent of patients may progress to incurable metastatic disease. 3 Risk of recurrence is greatest within the initial years post-diagnosis, particularly in patients with node-positive high-risk EBC.8

About abemaciclib

Abemaciclib is an oral inhibitor of cyclin-dependent kinases (CDK)4 & 6, which are activated by binding to D-cyclins. In oestrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4 & 6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.

Abemaciclib in combination with endocrine therapy is indicated for the adjuvant 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. In pre- or perimenopausal women, aromatase inhibitor endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.

Abemaciclib is also authorised for use but not reimbursed for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a LHRH agonist.

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