Novartis UK has announced that the Medicines and Healthcare products Regulatory Agency (MHRA) have authorised a new indication for ribociclib as an adjuvant treatment option to be used in combination with an AI for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer at high risk of recurrence.
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In pre- or perimenopausal women, or in men, the AI should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.
Breast cancer is the most common cancer in the UK, accounting for nearly 15% of all new cancer cases, and HR+/HER2- is the most common subtype found in 70% of all breast cancers in Europe. Despite current treatment options, people with HR+/HER2- eBC remain at risk of experiencing a return of their cancer in the long term, often as incurable advanced disease.
"The possibility of breast cancer returning can be a continuous concern for people who have been diagnosed with the disease. Therefore, providing an additional layer of protection to a broad population of patients at high risk of recurrence is always reassuring." said Stephen Johnston, Professor of Breast Cancer Medicine, Consultant Medical Oncologist, and Head of the Breast Unit at the Royal Marsden NHS Foundation Trust. "The introduction of ribociclib as a treatment option for early-stage breast cancer to reduce the risk of recurrence is a promising development for both clinicians and patients, including those with node-negative disease and additional risk factors."
The approval is based on results from the Phase III NATALEE trial, which included pre-/postmenopausal women and men with HR+/HER2- with any lymph node involvement (excluding microscopic nodal involvement), or if no nodal involvement either tumour size >5 cm, or tumour size 2-5 cm with either grade 2 (and high genomic risk or Ki67 ≥20%) or grade 3. The trial showed a significant and clinically meaningful 25.1% (HR 0.749, 95% CI 0.628-0.892; p = 0.0012) reduction in invasive disease-free survival (IDFS) events versus using aromatase inhibitor alone. iDFS at 3 years was 90.7% (95% CI 89.3%-91.8%) versus 87.6% (95% CI 86.1%-88.9%) respectively (absolute reduction: 3.1%).
There were no new safety signals reported in the final analysis of the NATALEE trial. The most common adverse drug reactions (ADRs) (reported at a frequency ≥20%) in the dataset for which the frequency for ribociclib plus aromatase inhibitor (AI) exceeds the frequency for AI alone were neutropenia, infections, nausea, headache, fatigue, leukopenia and abnormal liver function tests. The most common grade 3/4 ADRs (reported at a frequency of ≥2%) in the dataset for which the frequency for ribociclib plus AI exceeds the frequency for AI alone were neutropenia, abnormal liver function tests and leukopenia.
With the most recent analysis of the NATALEE trial data announced at ESMO, Novartis continues to evaluate NATALEE patients for longer-term outcomes, including overall survival.
“The announcement reinforces Novartis' 30-year legacy in driving scientific advancements for people affected by breast cancer. With consistent results across patient subgroups, ribociclib is now licensed for a broad population of patients diagnosed with HR+/HER2- eBC at high risk of recurrence,” said Gerrit Zijlstra, chief medical officer for the UK & Ireland at Novartis. “The MHRA decision builds on the confidence established by the NATALEE trial and highlights the potential of ribociclib to reduce the risk of recurrence in eBC, addressing a significant unmet need for patients in the UK.”
The MHRA licence in the UK comes shortly after the European Medicines Agency (EMA) approval for ribociclib across Europe. Following MHRA authorisation, the National Institute for Health and Care Excellence (NICE) and Scottish Medicines Consortium (SMC) submissions are under review to secure reimbursement of ribociclib to increase patient access via the National Health Service (NHS).