NICE recommends Novartis’ Kisqali® (ribociclib) for eligible HR+/HER2- early breast cancer patients at high risk of recurrence

NICE recommends Novartis’ Kisqali^® (ribociclib) for eligible HR+/HER2- early breast cancer patients at high risk of recurrence  

• The National Institute for Health and Care Excellence (NICE) has published final draft guidance recommending ribociclib, within its marketing authorisation, as an adjuvant treatment option to be used in combination with an aromatase inhibitor (AI) for all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 recurrence¹.

• The guidance recommends ribociclib for the full licensed patient population, meaning more eligible patients with HR+/ HER2- eBC can now receive a CDK4/6 inhibitor in the adjuvant setting. This includes patients who until now have had limited treatment options to reduce their risk of recurrence^1,2

• 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 cancers⁴

• People treated for HR+/HER2- early breast cancer remain at risk of experiencing a return of their cancer, often as incurable advanced disease^5,6. Adjuvant therapy is a type of cancer treatment given after the initial treatment to eliminate remaining cancer cells and reduce the risk of cancer returning

London, 17 July, 2025 – Novartis Pharmaceuticals UK announced today 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^1,7.

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 ⁴. 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.^5,6

“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 disease¹.

“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 3^7,8.

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)^9,10.

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 up¹⁰.

“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 patients¹¹.

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 Scotland¹².

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About NATALEE

NATALEE is a global Phase III multi-centre, randomised, open-label trial to evaluate the efficacy and safety profile of ribociclib with AI as an investigational adjuvant treatment versus AI alone, in patients with stage II and III HR+/HER2- eBC, being conducted in collaboration with TRIO. Pre-/perimenopausal women and men in both groups were also treated with an LHRH agonist. 

The adjuvant AI in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardised Definitions for Efficacy End Points (STEEP) criteria. A total of 5,101 adult patients with HR+/HER2- eBC across 20 countries were randomised in the trial.^9,13

About ribociclib

Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too fast. Targeting CDK4/6 proteins may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.⁷

In the UK, Ribociclib is licensed in combination with an aromatase inhibitor for the adjuvant treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer at high risk of recurrence (see section 5.1 for selection criteria). In pre- or perimenopausal women, or in men, the aromatase inhibitor should be combined with a luteinising hormone-releasing hormone (LHRH) agonist⁷.

It is also licensed for the treatment of women with HR-positive, 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.⁷

About Novartis

Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. 

In the UK, we champion health and lives through pioneering NHS partnerships, innovative collaborations and a clear focus on the greatest healthcare challenges we all face. We are where science meets hope.

To reimagine medicine with us, visit our website at https://www.novartis.com/uk-en/ and connect on LinkedIn, Facebook, and Instagram.

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References

1. National Institute for Health and Care Excellence (NICE) final draft guidance, Ribociclib with an aromatase inhibitor for adjuvant treatment of hormone receptor-positive HER2-negative early breast cancer at high risk of recurrence. Available at Project documents | Ribociclib with an aromatase inhibitor for adjuvant treatment of hormone receptor-positive, HER2-negative early breast cancer [ID6153] | Guidance | NICE.
2. Tarantino P, Rugo HS, Curigliano G, et al. Characteristics of real-world NATALEE and monarchE eligible populations: A US electronic health records database analysis. Poster presented at the European Society for Medical Oncology Congress; September 13-17, 2024; Barcelona, Spain
3. Cancer incidence for common cancers | Cancer Research UK https://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/common-cancers-compared Accessed July, 2025
4. Peter A Fasching et al. Identification of Patients with Early HR+ HER2− Breast Cancer at High Risk of Recurrence. National Library of Medicine. 2024
5. Pan H, Gray R, Braybrooke J, et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med. 2017;377(19):1836–1846.
6. Gomis RR, Gawrzak S. Tumor cell dormancy. Mol Oncol. 2017;11(1):62–78.
7. Ribociclib Summary of Product Characteristics
8. Hortobagyi GN et al. A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial. Ann Oncol. 2025 Feb;36(2):149-157.
9. Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med. 2024;390(12):1080–1091.
10. Fasching PA, et al. Oral LBA13. Presented at the European Society for Medical Oncology Congress 2024 (13–17 September; Barcelona, Spain).
11. Project documents | Ribociclib with an aromatase inhibitor for adjuvant treatment of hormone receptor-positive, HER2-negative early breast cancer [ID6153] | Guidance | NICE
12. Scottish Medicines Consortium: Accessed June 2025. https://scottishmedicines.org.uk/medicines-advice/ribociclib-kisqali-full-smc2803/
13. gov. NCT03701334. A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/ HER2- Early Breast Cancer (NATALEE). Updated October 10, 2024. Available from: https://clinicaltrials.gov/study/NCT03701334#study-overview. Accessed December, 2024.