Abemaciclib in combination with endocrine therapy is the first CDK4/6 inhibitor to be made available within NHS England following the recommendation from NICE for people with HR+, HER2-, node-positive early breast cancer at high-risk of recurrence. 

Adjuvant treatment with abemaciclib in combination with endocrine therapy decreased the risk of breast cancer recurrence by 32%. 

Approximately 20-30% of people with HR+, HER2- early breast cancer develop incurable metastatic disease.

The recommendation of abemaciclib as adjuvant treatment will provide a new treatment option for people with breast cancer that have a high risk of recurrence.

Eli Lilly and Company announced today that the National Institute for Health and Care Excellence (NICE) have recommended abemaciclib in combination with endocrine therapy, within its marketing authorisation, as an option for adjuvant treatment of hormone receptor-positive, HER2-negative, node-positive 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:
• grade 3 disease (defined as at least 8 points on the modified Bloom-Richardson grading system or equivalent), or
• primary tumour size of at least 5 cm. 

Abemaciclib is recommended subject to a confidential commercial arrangement.

This positive NICE recommendation means that abemaciclib is now available for use in NHS England via interim funding by the Cancer Drugs Fund until routine NHS baseline funding is in place.1

Today’s news comes just 4 weeks after the MHRA granted marketing authorisation for this indication in Great Britain. 

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 compelling results from the monarchE trial, which was a huge international effort, translate into a new treatment option for HR+ and HER2- breast cancer patients who have a high risk of their cancer recurring. Despite previously receiving the very best standard of care treatment, this high risk node-positive group represents about 5,000 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 new treatment for this patient group in 20 years. I’m delighted that it will be available on the NHS for eligible patients to help reduce their risk of recurrence.”

“The NICE recommendation establishes abemaciclib as the first CDK4/6 inhibitor to be made available in the NHS for the treatment of HR+, HER2-, high risk early breast cancer and is the first successful addition to adjuvant ET in nearly two decades,” said Dr Jeff Yang, Associate Vice President – Medical, Northern Europe, Eli Lilly and Company. “This is encouraging news for patients and exciting to see the decision so quickly after receiving marketing authorisation in May, with the UK one of the first countries in the world to recommend access for patients.”

This recommendation 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.

In a further exploratory analysis with 91% of patients in Cohort 1 off the 2 years study treatment, 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).

This was consistent across all pre-specified subgroups and corresponds to a three percent difference in IDFS between arms (92.6 percent in the abemaciclib arm and 89.6 percent in the control arm) at two years.

Safety data from monarchE were consistent with the known safety profile of abemaciclib and no new safety signals were observed.

The most common adverse events (>10%) were diarrhoea, neutropenia, fatigue, leukopenia, abdominal pain, nausea, anaemia, arthralgia, hot flush, lymphopenia, thrombocytopenia, vomiting, constipation, upper respiratory tract infection, urinary tract infection, decreased appetite, headache, cough, and lymphoedema.

Reasons for discontinuations include diarrhoea (5.3%), fatigue (2.0%), and neutropenia (0.9%). 

Many of the discontinuations due to AEs occurred in the early months of treatment.

Most patients who required a dose hold or reduction after an AE were able to remain on study treatment.

MonarchE randomised 5,637 patients with HR+, HER2-, high risk EBC from more than 600 sites in 38 countries.

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).

The recommendation of abemaciclib in HR+, HER2- EBC builds on the established profile for abemaciclib, which has previously been recommended for the treatment of HR+, HER2- advanced or metastatic breast cancer.

Source: Eli Lilly