On December 10, 2024 Novartis reported results from an updated analysis of the pivotal Phase III NATALEE trial of Kisqali (ribociclib) that underscore the extended efficacy beyond the duration of treatment in combination with endocrine therapy (ET) (Press release, Novartis, DEC 10, 2024, View Source [SID1234649002]). Results showed a sustained reduction in distant recurrence of 28.5% (HR=0.715; 95% CI 0.604-0.847; nominal P<0.0001), compared to ET alone, in patients with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC)1.
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Reduction in distant recurrence, known as distant disease-free survival (DDFS), is a decrease in the rate of cancer returning and spreading to other organs. The DDFS with Kisqali was consistent across all pre-specified patient subgroups, including those with node-negative (N0) disease1. These late-breaking data are being presented at the 2024 San Antonio Breast Cancer Symposium (SABCS).
"In day-to-day practice, we see a real and persistent risk of breast cancer coming back after early diagnosis, often as metastatic disease," said Paolo Tarantino, M.D., Advanced Fellow at Dana-Farber Cancer Institute and Harvard Medical School. "The latest NATALEE and real-world data presented at SABCS reaffirm we can better address risk of recurrence for all patients at high-risk, including selected patients with node-negative disease, by offering them adjuvant CDK4/6 inhibitor treatment in addition to endocrine therapy."
DDFS results across pre-specified subgroups1,4**:
Subgroup Hazard Ratio 95% CI
Intention-To-Treat Population 0.715 0.604-0.847
AJCC Tumor Stage IIA 0.396 0.218-0.720
AJCC Tumor Stage IIB 0.806 0.524-1.238
AJCC Tumor Stage IIIA 0.697 0.524-0.926
AJCC Tumor Stage IIIB 0.569 0.326-0.994
AJCC Tumor Stage IIIC 0.878 0.649-1.188
Node-negative disease 0.696 0.403-1.204
Node-positive disease 0.726 0.608-0.867
Safety remains consistent with previous reports, and no new safety signals were identified5. Adverse events (AEs) of special interest (grade 3 or higher) were neutropenia (44.4%), liver-related AEs (e.g., elevated transaminases) (8.6%), and QT interval prolongation (1.0%)5.
Real-World Risk of Distant Recurrence
Further, real-world evidence presented at the meeting highlights the relatively high incidence of distant recurrences within 5 years despite ET monotherapy for patients at high-risk, regardless of nodal involvement2.
"On the heels of its U.S. FDA and EMA approvals in early breast cancer, it is encouraging to see the continued benefit of adding Kisqali to standard endocrine therapy to help reduce the risk of recurrence," said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. "These data, together with the recent NCCN Guidelines Category 1 preferred treatment recommendation for all eligible patients with early breast cancer, reinforce the opportunity to evolve adjuvant treatment to help a broader group of people."
Additional research presented at the meeting further demonstrates the ongoing focus of Novartis to advance the care of people with breast cancer, including studies investigating the potential of radioligand therapies in the treatment of metastatic breast cancer (MBC)6.
*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
**The 4-year DDFS analysis was not prespecified and the trial was not powered to demonstrate statistical significance of these results.
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 investigational adjuvant treatment versus ET alone in patients with stage II and III HR+/HER2- EBC, being conducted in collaboration with TRIO7,8. The adjuvant ET in both treatment arms was a non-steroidal aromatase inhibitor (NSAI; anastrozole or letrozole) and goserelin if applicable7,8. The primary endpoint of NATALEE is invasive disease-free survival (iDFS) as defined by the Standardized Definitions for Efficacy End Points (STEEP) criteria7,8. A total of 5,101 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial7,8.
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.
Kisqali has been approved as a treatment for breast cancer by regulatory authorities in 99 countries worldwide, including the U.S. FDA and the European Commission9,10. 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 ET in post-menopausal women or in men9. In the EU, Kisqali is approved 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 progression10. In pre- or peri-menopausal women, the ET should be combined with a luteinizing hormone-releasing hormone agonist9,10.
In EBC, ribociclib (Kisqali) is the only CDK4/6 inhibitor recommended by the NCCN Guidelines for breast cancer 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 33. In MBC, Kisqali has consistently demonstrated statistically significant overall survival benefit across three Phase III trials11-21. The NCCN Guidelines also 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 AI3, making Kisqali the preferred first-line treatment of choice for US prescribers in HR+/HER2- MBC.
In addition, Kisqali has achieved the highest score (A) on the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) for EBC22; and has the highest rating of any CDK4/6 inhibitor on the ESMO (Free ESMO Whitepaper) Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line pre-menopausal patients with HR+/HER2- advanced breast cancer23. 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 line24.
Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals.
Please see full Prescribing Information for Kisqali, available at www.Kisqali.com