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  • Broad indication in HR+/HER2- stage II and III early breast cancer (EBC) at high risk of recurrence approximately doubles population eligible for CDK4/6 inhibitor adjuvant therapy1,2
  • Kisqali® (ribociclib) significantly reduced the risk of recurrence by 25% vs. endocrine therapy (ET) alone; consistent benefit and a well-tolerated safety profile seen across all sub-groups in pivotal Phase III NATALEE trial, including patients with node-negative disease3-6
  • Late-breaking NATALEE data recently presented at ESMO provides additional confidence, with deepening of invasive disease-free survival benefit after completion of the three-year treatment period across all patient subgroups7
  • People with stage II or III HR+/HER2- EBC face significant risk of recurrence – often as incurable metastatic disease – despite adjuvant ET and regardless of nodal involvement8,9
  • Already a proven treatment in HR+/HER2- metastatic breast cancer1,10-20, Kisqali is under regulatory review worldwide, including in the EU, for the EBC indication

EAST HANOVER, NJ, USA I September 17, 2024 I Novartis today announced that the US Food and Drug Administration (FDA) has approved Kisqali® (ribociclib) in combination with an aromatase inhibitor (AI) for the adjuvant treatment of people with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) stage II and III early breast cancer (EBC) at high risk of recurrence, including those with node-negative (N0) disease1.

The approval is based on results from the pivotal Phase III NATALEE trial, which showed a significant and clinically meaningful 25.1% (HR=0.749; 95% CI: 0.628, 0.892; P=0.0006) reduction in risk of disease recurrence in a broad population of patients with HR+/HER2- stage II and III EBC treated with adjuvant Kisqali plus endocrine therapy (ET) compared to ET alone, including those with high-risk N0 disease3-6. The invasive disease-free survival (iDFS) benefit was consistently observed across all patient subgroups3-6.

“The FDA approval of Kisqali for this early breast cancer population, including those with N0 disease, is a pivotal moment in improving our approach to care,” said Dennis J. Slamon, M.D., Director of Clinical/Translational Research, UCLA Jonsson Comprehensive Cancer Center and Chairman of the Board of Translational Research In Oncology (TRIO) and NATALEE trial lead investigator. “Today’s approval allows us to offer treatment with a CDK4/6 inhibitor to a significantly broader group of people as a powerful tool that, combined with endocrine therapy, can help further minimize their risk of cancer returning.”

In EBC, Kisqali is taken with or without food as a once-daily oral dose of 400 mg (two 200 mg tablets) for three weeks, followed by one week off treatment, in combination with four weeks of any AI1. Patients should take Kisqali for three years. The NATALEE trial showed the safety profile of Kisqali at the 400 mg dose was well tolerated, with discontinuations mainly driven by asymptomatic laboratory findings3. Adverse events (AEs) of special interest in the Kisqali + ET arm of the NATALEE trial include (all Grades, and Grades 3/4, respectively): neutropenia (62.5%, 44.3%), liver-related AEs (26.4%, 8.6%), QT interval prolongation (5.3%, 1.0%), and interstitial lung disease/pneumonitis (1.5%, 0.0%)4.

An updated analysis from the NATALEE trial recently presented at the European Society for Medical Oncology (ESMO) Congress 2024 reinforces the data analyzed by the FDA. Results showed a deepening benefit beyond the three-year treatment period and reduced the risk of recurrence by 28.5% (HR=0.715; CI 95% 0.609-0.840; P<0.0001), compared to ET alone, in patients with stage II and III HR+/HER2- EBC7. Novartis will continue evaluating NATALEE patients for longer-term outcomes, including overall survival.

Raising the bar for EBC survivors
Approximately 90% of breast cancer cases in the US are diagnosed early (stages I-III) and treated promptly with curative intent – sometimes with adjuvant ET21,22. In spite of this, people with stage II and III HR+/HER2- EBC remain at risk of cancer coming back – in most cases, as incurable metastatic disease8,9. Recurrence remains a lifelong concern, though most tumors return within the first years, even in cases with no lymph node involvement8,23. Despite ET, 10% of people with high-risk N0 disease may face recurrence within the first three years after diagnosis24.

“With this approval, we are redefining treatment options for a broader population of people impacted by breast cancer and facing the persistent risk of recurrence,” said Victor Bultó, President, US, Novartis. “We continue to transform cancer care with Kisqali, building on its established profile in the metastatic setting and now helping a wide range of people as they strive to stay cancer-free following an early-stage diagnosis.”

“Breast cancer treatment can take a toll on your physical and mental health, and you may worry about the risk of your cancer coming back. This risk is different for everyone, depending on many factors, but should not be underestimated,” said Valarie Worthy, Co-Founder & Vice President of Community Outreach and Engagement, Touch, The Black Breast Cancer Alliance. “The FDA approval of Kisqali for more people with breast cancer is welcome news and empowers people diagnosed with early breast cancer with a new option to help manage and control their risk of cancer coming back.”

Novartis prioritizes patient access by offering the Kisqali patient support program. This resource assists eligible patients in navigating treatment initiation, providing educational materials, clarifying insurance coverage, and identifying potential financial assistance options. For additional information, patients and healthcare professionals can call 1-800-282-7630.

About NATALEE
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of Kisqali® (ribociclib) with ET as an investigational adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO25. The adjuvant ET in both treatment arms was a non-steroidal AI (NSAI; anastrozole or letrozole) and goserelin if applicable25. The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria25. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial25.

About Kisqali® (ribociclib)
Kisqali® (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 quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Beyond today’s FDA approval of Kisqali for EBC patients in the US, regulatory reviews for Kisqali as an EBC treatment are ongoing worldwide, including in the EU and China. 

Kisqali has been approved as a treatment for metastatic breast cancer (MBC) patients in 99 countries worldwide, including by the US FDA and the European Commission1,26. In the US, Kisqali is indicated for the treatment of adults with HR+/HER2- advanced or MBC in combination with an AI as initial ET or fulvestrant as initial ET or following disease progression on ET in post-menopausal women or in men1.

In MBC, Kisqali has consistently demonstrated statistically significant overall survival benefit across three Phase III trials10-20. The NCCN Guidelines® for breast cancer recommend ribociclib (Kisqali) as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of people living with HR+/HER2- when combined with an AI, making Kisqali the preferred first-line treatment of choice for US prescribers in HR+/HER2- MBC27.

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 35 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.

Indication

What is KISQALI?

KISQALI® (ribociclib) is a prescription medicine used to treat adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer:

  • in combination with an aromatase inhibitor for stage II and III early breast cancer with a high risk of coming back
  • that has gotten worse or has spread to other parts of the body (advanced or metastatic breast cancer) in combination with:
    • an aromatase inhibitor as the first endocrine-based therapy; or
    • fulvestrant as the first endocrine-based therapy or following disease progression on endocrine therapy

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. Our medicines reach more than 250 million people worldwide.

Reimagine medicine with us: Visit us at https://www.novartis.com and https://www.novartis.us, and connect with us on LinkedIn, LinkedIn US, Facebook, X/Twitter, X/Twitter US and Instagram.

References

  1. Kisqali (ribociclib) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; September 2024.
  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. Slamon D, Stroyakovskiy D, Yardley D, et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2− early breast cancer: primary results from the Phase III NATALEE trial. Presented at the American Society of Clinical Oncology Annual Meeting; June 2, 2023; Chicago, USA.
  4. Hortobagyi G, Stroyakovskiy D, Yardley DA, et al. Ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) as adjuvant treatment in patients with HR+/HER2- early breast cancer: final invasive disease-free survival (iDFS) analysis from the NATALEE trial. Presented at San Antonio Breast Cancer Symposium (SABCS); December 8, 2023; San Antonio, USA.
  5. Slamon D et al. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med. 2024;390:1080-1091. doi: 10.1056/NEJMoa2305488
  6. Yardley D, Untch M, et al. Baseline (BL) characteristics and efficacy endpoints for patients (pts) with node-negative (N0) HR+/HER2− early breast cancer (EBC) in NATALEE. Presented at the American Society of Clinical Oncology Annual Meeting; May 31, 2024; Chicago, USA.
  7. Fasching PA. Adjuvant Ribociclib (RIB) Plus Nonsteroidal Aromatase Inhibitor (NSAI) in Patients (Pts) With HR+/HER2− Early Breast Cancer (EBC): 4-Year Outcomes From the NATALEE Trial. LBA13. Proffered Paper presented at the European Society for Medical Oncology Congress; September 16, 2024; Barcelona, Spain.
  8. Pan H et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med. 2017;377 (suppl 19):1836 846. doi: 10.1056/NEJMoa1701830
  9. Wangchinda P, Ithimakin S. Factors that predict recurrence later than 5 years after initial treatment in operable breast cancer. World J Surg Oncol. 2016;14(1):223. doi: 10.1186/s12957-016-0988-0
  10. Yardley DA, Yap YS, 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.
  11. Neven P, Fasching PA, 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.
  12. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. New England Journal of Medicine. 2022;386(10):942-950. doi:10.1056/NEJMoa2114663 
  13. 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. Proffered paper presented at the European Society of Medical Oncology Congress; September 16-21, 2021; Lugano, Switzerland. 
  14. Im S-A, Lu Y-S, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. New England Journal of Medicine. 2019;381(4):307-316. doi:10.1056/nejmoa1903765
  15. Slamon DJ, Neven P, Chia S, et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. New England Journal of Medicine. 2020;382(6):514-524. doi:10.1056/NEJMoa1911149
  16. Slamon DJ, Neven P, Chia S, 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). Presented at the European Society of Medical Oncology Congress; September 29, 2019; Barcelona, Spain.
  17. Slamon DJ, Neven P, Chia S, 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.
  18. Tripathy D, Im S-A, Colleoni M, 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.
  19. Yardley D, Nusch A, Yap YS, 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 (ASCO) Annual Meeting; June 2020; Chicago, USA.
  20. O’Shaughnessy J, Stemmer SM, Burris HA, et al. Overall survival subgroup analysis by metastatic site from the Phase III MONALEESA-2 study of first-line ribociclib + letroz21ole in postmenopausal patients with HR+/HER2− advanced breast cancer. Presented at the San Antonio Breast Cancer Symposium; December 7-10, 2021; Texas, USA.
  21. Iqbal J, Ginsburg O, Rochon PA, Sun P, Narod SA. Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States [published correction appears in JAMA. 2015 Jun 9;313(22):2287]. JAMA. 2015;313(2):165-173. doi:10.1001/jama.2014.17322
  22. American Cancer Society. Cancer Facts and Figures. Published 2024. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf. Accessed September 2024.
  23. Gomis R, Gawrzak S. Tumor cell dormancy. Mol Oncol. 2017;11(1):62-78.
  24. Curigliano G, Ciruelos E, et al. Meta analysis of ET control arms in adjuvant trials. Presented at the American Society of Clinical Oncology Annual Meeting, May 31, 2024. Chicago, USA.
  25. 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 September 2024. https://clinicaltrials.gov/study/NCT03701334
  26. Kisqali. Summary of product characteristics (SmPC). Novartis Europharm Limited; 2017. Accessed September 2024. https://www.ema.europa.eu/en/documents/product-information/kisqali-epar-product-information_en.pdf.
  27. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) – Breast Cancer. NCCN Guidelines. Published March 2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 2024.

SOURCE: Novartis

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