Eli Lilly and Company announced today that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation (MA) for abemaciclib in combination with endocrine therapy 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.ⁱⁱⁱ  

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 – about 15% of all HR+ and HER2- breast cancer patients – were at considerable risk of their disease returning. This drug represents a significant breakthrough and I’m delighted that it will be available for eligible patients to help reduce their risk of recurrence.”  

“This approval establishes abemaciclib as the first CDK4/6 inhibitor to be authorised 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, Northern Europe, Eli Lilly and Company. “We understand the importance of having treatment options and are proud abemaciclib is now available for patients. Lilly would like to thank the patients and investigators around the world, including those in the United Kingdom who have made this possible.” 

This authorisation 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.^iv   

·       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.¹  

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%).^v 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.^4,vi  

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  

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