Novartis Pharmaceuticals UK announced that the National Institute for Health and Care Excellence (NICE) has recommended ribociclib, within its marketing authorisation, as an adjuvant treatment option to be used in combination with an aromatase inhibitor (AI) for all eligible patients with HR+/HER2- early breast cancer (eBC) at high risk of recurrence (see section 5.1 of the summary of product characteristics for selection criteria).

In pre- or perimenopausal women, or in men, the aromatase inhibitor should be combined with a luteinising hormone-releasing hormone (LHRH) agonist. Ribociclib is recommended only if provided according to the commercial arrangement.

Breast cancer is the most common cancer in the UK, accounting for nearly 15% of all new cancer cases3. HR+/ HER2- breast cancer is the most prevalent subtype and is found in around 70% of all breast cancers. Despite initial treatment, people with HR+/HER2- eBC remain at risk of experiencing a return of their cancer, often as incurable advanced or metastatic disease.

“Cancer remission is often perceived as the final step, but for many patients it’s the beginning of a new chapter, one where the possibility of their disease coming back can be a constant concern. This fear is not only prevalent but also persistent, often affecting mental health, relationships, and daily activities. It is encouraging to see that a broad population of patients with early breast cancer now have access to an additional treatment that will reduce the risk of their cancer recurring” – says Kirstin Spencer, Independent Cancer Patients' Voice.

NICE final draft guidance recommends ribociclib as an adjuvant treatment for a broad population of patients diagnosed with HR+/HER2- eBC at high risk of recurrence. The treatment is an additional CDK4/6 inhibitor option that can be prescribed for early breast cancer patients whose cancer has spread to the lymph nodes. It is the only CDK4/6 inhibitor recommended in combination with AI for eligible patients with any lymph node involvement (excluding microscopic nodal involvement) and patients with no nodal involvement and high-risk disease.

“HR+/HER2- is the most common breast cancer subtype. Despite all the advances we have to offer, including endocrine therapy, risk of recurrence remains a concern,” says Stephen Johnston, Professor of Breast Cancer Medicine and Head of the Breast Unit at the Royal Marsden NHS Foundation Trust. “CDK4/6 inhibitors help minimise this risk by reducing cell turnover. We now have an additional option that benefits a broader group, including N1 and high-risk N0 patients. Identifying these patients at residual risk is essential, so we can act early to prevent recurrence."

The recommendation is based on results from the Phase III NATALEE trial, which included 5,101 pre-/postmenopausal women and men with HR+/HER2- breast cancer 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 37,8.

The primary endpoint of the study was met at the primary analysis (11 January 2023 cut-off). A statistically significant improvement in iDFS (HR: 0.748, 95% CI: 0.618, 0.906; one-sided stratified log-rank test p-value 0.0014) was demonstrated in patients receiving ribociclib plus AI over AI alone. Consistent results were observed across sub-groups of anatomic stage, menopausal status, region, nodal status, age, race, and prior adjuvant/neo-adjuvant chemotherapy or hormonal therapies. An exploratory 4-year landmark analysis of NATALEE demonstrated a 28.5% reduction in the relative risk of iDFS events compared with AI alone (4.9% absolute risk reduction).

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 leukopenia7. The safety profile remained stable with additional follow up.

“We welcome NICE’s recommendation enabling access to ribociclib for more patients with early-stage breast cancer. This marks a step forward in expanding treatment options for people diagnosed with HR+/HER2- early breast cancer,” said Johan Kahlström, President & Managing Director Novartis UK & Ireland. “Previously only available under the NHS for patients with locally advanced and metastatic disease, ribociclib can now be used to treat eligible women and men with early HR+/HER2- breast cancer and high risk of recurrence—regardless of nodal involvement and across eligible pre-, peri-, and post-menopausal populations.”

NICE’s positive recommendation follows April’s draft guidance recommending ribociclib for an optimised population with HR+/HER2- eBC, allowing immediate access via the interim cancer drugs fund (CDF) for these eligible patients. 

Following the NICE recommendation, the guidance should be adopted by the NHS in Wales and Northern Ireland. The Scottish Medicines Consortium (SMC) submission is under review to secure reimbursement of ribociclib to enable patient access via the National Health Service (NHS) in Scotland.

Source: Novartis