Novartis Kisqali® 5-year NATALEE data demonstrate 28% reduction in risk of recurrence in the broadest early breast cancer patient population

• After 5 years, Kisqali^® plus endocrine therapy consistently shows significant and clinically meaningful benefit in invasive disease-free survival¹
• Kisqali remains the only CDK4/6 inhibitor demonstrating consistent and clinically meaningful benefit across the broadest population of HR+/HER2- early breast cancer (EBC) patients, including those with node-negative disease¹  
• Data also show a 29.1% risk reduction in distant disease-free survival, and a positive trend in overall survival*¹   
• With a median of around two years post-completion of treatment with Kisqali, no new safety signals were observed¹

Basel, October 17, 2025 – Novartis today announced results from the five-year analysis of the pivotal Phase III NATALEE trial of Kisqali^® (ribociclib) that demonstrated a sustained benefit at a median of two years after a three-year treatment with Kisqali (median follow-up: 58.4 months). Results showed a 28.4% reduction in risk of recurrence (HR=0.716; 95% CI 0.618-0.829; nominal p-value <0.0001) in the broadest population of patients with high-risk stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) treated with Kisqali plus endocrine therapy (ET) compared to ET alone¹. 

The five-year invasive disease-free survival (iDFS) rates were 85.5% in the Kisqali plus ET arm versus 81.0% in the ET alone arm, representing a clinically meaningful 4.5% improvement¹. These late-breaking results will be presented at the European Society for Medical Oncology (ESMO) Congress 2025.

“For the thousands of people diagnosed with early breast cancer each year, the fear of recurrence, often as incurable advanced disease, weighs heavily on patients and their families,” said Dr. John Crown, Consultant Medical Oncologist at St. Vincent’s University Hospital, Dublin, and NATALEE investigator. “These five-year results show that the benefit of ribociclib persists well beyond the completion of treatment, offering these at-risk patients a greater chance of living breast cancer-free.”

As follow-up continued, the confidence intervals (CIs) became narrower¹. This pattern held across clinically relevant subgroups, reinforcing the robustness of the observed iDFS benefit¹.  

“These data reinforce the potential of Kisqali to significantly reduce the long-term risk of breast cancer recurrence, extending well beyond the three-year treatment period. This provides physicians and patients with greater confidence in long-term disease management. Kisqali is redefining the standard of care in adjuvant therapy, including in patients with node-negative disease,” said Dushen Chetty, Global Head of Oncology and Hematology Development at Novartis, Ad Interim. “The consistency of the benefit observed across both advanced and early breast cancer settings, together with Kisqali’s established safety profile, underscores its position as the CDK4/6 inhibitor with the most comprehensive Phase III evidence base for improving patient outcomes.”

Overall survival (OS) continues to show an encouraging trend, with further improvement in the hazard ratio (HR) to 0.800 and narrowing CI (95% CI: 0.637-1.003; one-sided nominal p-value 0.026) compared to the final iDFS analysis (OS HR = 0.892 (0.661-1.203)), demonstrating a 20% reduction in the risk of death compared to ET alone¹. The NATALEE trial will continue follow-up to ensure sufficient data is collected for OS and other long-term endpoints.

iDFS results across pre-specified subgroups¹:

With a median of around two years after all patients completed Kisqali treatment, long-term safety shows no new safety signals¹. Overall, rates of secondary primary malignancies (SPMs) were 2.7% (Kisqali plus ET) and 3.0% (ET alone), while SPMs leading to deaths were reported in one patient in each group¹. 

Kisqali remains the only CDK4/6 inhibitor to demonstrate statistically significant OS benefits across three randomized controlled trials in advanced breast cancer (MONALEESA-2, MONALEESA-3, and MONALEESA-7)^2-12.

*OS data remain immature at the five-year NATALEE analysis

About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali with ET as an adjuvant treatment versus ET alone in the broadest range of patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO^13,14. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable^13,14. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria^13,14. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial^13,14.

About Kisqali^® (ribociclib)
Kisqali^® (ribociclib) is a selective cyclin-dependent kinase inhibitor, helping slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, enable cancer cells to grow and divide quickly. Targeting CDK4/6 with enhanced precision plays a role in tumor control.

Kisqali has been approved as a treatment for breast cancer by regulatory authorities in more than 100 countries worldwide, including the U.S. FDA and the European Commission^15,16. In the US, Kisqali is indicated in combination with an AI as an adjuvant treatment for adults with HR+/HER2- stage II and III early breast cancer at high risk of recurrence, as well as for the treatment of adults with HR+/HER2- advanced or MBC as initial ET; Kisqali is also approved in the metastatic indication in combination with fulvestrant as initial ET or following disease progression on ET¹⁵. In the EU, Kisqali is approved in combination with an AI for the adjuvant treatment of patients with HR+/HER2- early breast cancer at high risk of recurrence; and for the treatment of women with HR+/HER2- advanced or MBC in combination with either an AI or fulvestrant as initial ET or following disease progression¹⁶. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist^15,16.

In EBC, Kisqali is the only CDK4/6 inhibitor recommended by the NCCN Guidelines^® for breast cancer as Category 1 preferred for both all node-positive disease as well as for patients with no nodal involvement with high-risk disease characteristics, such as tumor size >5 cm, or for tumors sized 2-5 cm, either Grade 2 with high genomic risk/Ki-67 ≥20% or Grade 3¹⁷. Kisqali approvals in EBC from regulatory authorities worldwide are ongoing, including recent approval from China’s National Medical Products Administration¹⁸. In MBC, Kisqali has consistently demonstrated statistically significant overall survival benefit across three Phase III trials^2-12. The NCCN Guidelines^® also recommend Kisqali as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of people living with HR+/HER2- MBC when combined with an AI, making Kisqali the preferred first-line treatment of choice for US prescribers in HR+/HER2- MBC¹⁷.

In addition, Kisqali has achieved the highest score (A) on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) for EBC¹⁹; and has the highest rating of any CDK4/6 inhibitor on the ESMO Magnitude of Clinical Benefit Scale, achieving a score of four out of five for first-line pre-menopausal patients with HR+/HER2- advanced breast cancer²⁰. Further, Kisqali in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6 inhibitors, received a score of four out of five for post-menopausal patients with HR+/HER2- advanced breast cancer treated in the first line²¹.

Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals.

Please see full Prescribing Information for Kisqali, available at www.Kisqali.com

About Novartis in Breast Cancer
For more than 30 years, Novartis has been at the forefront of driving scientific advancements for people touched by breast cancer and improving clinical practice in collaboration with the global community. With one of the most comprehensive breast cancer portfolios and pipeline, Novartis leads the industry in discovery of new therapies and combinations in HR+/HER2- breast cancer, the most common form of the disease.

Disclaimer
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About Novartis
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References

1. Crown J, Stroyakovskii D, Yardley DA, et al. Adjuvant Ribociclib Plus Nonsteroidal Aromatase Inhibitor Therapy in Patients With HR+/HER2− Early Breast Cancer: NATALEE 5-Year Outcomes. Presented at the European Society for Medical Oncology (ESMO) Congress; October 17-21, 2025; Berlin, Germany.
2. Yardley DA et al. Pooled exploratory analysis of survival in patients (pts) with HR+/HER2- advanced breast cancer (ABC) and visceral metastases (mets) treated with ribociclib (RIB) + endocrine therapy (ET) in the MONALEESA (ML) trials. Poster presented at the European Society of Medical Oncology Congress. September 9-13, 2022. Paris, France.
3. Neven P et al. Updated overall survival (OS) results from the first-line (1L) population in the Phase III MONALEESA-3 trial of postmenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with ribociclib (RIB) + fulvestrant (FUL). Mini oral presented at the European Society for Medical Oncology Breast Cancer Congress. May 4, 2022. Paris, France.
4. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663.
5. Hortobagyi GN et al. Overall survival (OS) results from the phase III MONALEESA (ML)-2 trial of postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. LBA 17. Proffered paper presented at the European Society of Medical Oncology Congress, September 16-21, 2021. Lugano, Switzerland.
6. Im SA, Lu YS, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381(4):307-316. doi:10.1056/NEJMoa1903765.
7. Slamon DJ, Neven P, Chia S, et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020;382(6):514-524. doi:10.1056/NEJMoa1911149.
8. Slamon DJ et al. Overall survival (OS) results of the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). LBA7_PR. Presented at the European Society of Medical Oncology Congress. September 29, 2019. Barcelona, Spain.
9. Slamon DJ et al. Updated overall survival (OS) results from the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2− advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). Presented at the American Society of Clinical Oncology Annual Meeting. June 5, 2021. Chicago, USA.
10. Tripathy D et al. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Presented at the San Antonio Breast Cancer Symposium. December 9, 2020. Texas, USA.
11. Yardley D et al. Overall survival (OS) in patients (pts) with advanced breast cancer (ABC) with visceral metastases (mets), including those with liver mets, treated with ribociclib (RIB) plus endocrine therapy (ET) in the MONALEESA (ML) -3 and -7 trials. Presented at the American Society of Clinical Oncology Annual Meeting. June 2020. Chicago, USA.
12. O’Shaughnessy J et al. Overall survival subgroup analysis by metastatic site from the Phase III MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with HR+/HER2− advanced breast cancer. Presented at the San Antonio Breast Cancer Symposium. December 7-10, 2021. Texas, USA.
13. 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. doi:10.1056/NEJMoa2305488
14. Clinicaltrials.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). Accessed October 2025. https://clinicaltrials.gov/study/NCT03701334
15. Kisqali. Prescribing Information (US FDA). Novartis Pharmaceuticals Corporation; 2017. Accessed October 2025. https://www.novartis.com/us-en/sites/novartis_us/files/kisqali.pdf
16. Kisqali. Summary of product characteristics (SmPC). Novartis Europharm Limited; 2017. Accessed October 2025. https://www.ema.europa.eu/en/documents/product-information/kisqali-epar-product-information_en.pdf
17. NCCN Guidelines. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) – Breast Cancer. Accessed October 2025. https://www.nccn.org
18. National Medical Products Administration. Drug Evaluation Information Disclosure: Drug Evaluation Approval Results. National Medical Products Administration. Published May 21, 2025. Accessed October 2025. https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20250521151427103.html
19. European Society of Medical Oncology (ESMO). ESMO MCBS scorecards; NATALEE. Accessed October 2025. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards/scorecard-468-1
20. European Society for Medical Oncology. Magnitude of Clinical Benefit Scale Scorecard. Accessed October 2025. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards?scorecard=158-1
21. European Society for Medical Oncology. Magnitude of Clinical Benefit Scale Scorecard. Accessed October 2025. https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-for-solid-tumours/esmo-mcbs-scorecards?scorecard=9-1
     

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