Ribociclib Plus Aromatase Inhibitor Approved as Adjuvant Therapy for HR+/HER2- Early Breast Cancer
This approval offers an additional treatment option for a disease that can commonly return.
The FDA has approved ribociclib (Kisqali) in combination with an aromatase inhibitor as an adjuvant treatment for individuals with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) stage 2 and stage 3 early breast cancer, who are at high risk of recurrence—including those with node-negative disease.1
Approval followed results of the NATALEE clinical trial (NCT03701334), a pivotal phase 3, multicenter, randomized, open-label clinical trial evaluating the efficacy and safety of ribociclib plus endocrine therapy as an investigational adjuvant therapy vs endocrine therapy alone in this patient population. Data from NATALEE were presented at the American Society of Clinical Oncology Annual Meeting in June 2024 and at the San Antonio Breast Cancer Symposium in December 2023. Results were published in the New England Journal of Medicine2 earlier this year.
Ribociclib (Kisqali) offers another treatment option for those with stage 2 or stage 3 HR+/HER2- early breast cancer | image credit: Sebastian Kaulitzki - stock.adobe.com
A cohort of 5101 patients were randomly assigned to receive either ribociclib plus a nonsteroidal aromatase inhibitor—either letrozole 2.5 mg/day or anastrozole 1 mg/day—or a nonsteroidal aromatase inhibitor alone. The primary endpoint was invasive disease-free survival; secondary endpoints included distant disease-free survival, recurrence-free survival, overall survival, safety, quality of life, and pharmacokinetics, and exploratory endpoints included distant recurrence-free survival.
The data cutoff date for the prespecified interim analysis was January 11, 2023. At this time, a total of 236 patients had either invasive disease, recurrence, or death, and the risk for these outcomes was significantly and clinically meaningfully reduced by 25.2% in the ribociclib plus nonsteroidal aromatase inhibitor group compared with the nonsteroidal aromatase inhibitor group alone, including patient with node-negative disease. Additionally, an invasive disease-free survival benefit was consistently seen across all patient subgroups.
An additional analysis of data from NATALEE was presented at the European Society of Medical Oncology Congress in September 2024. These data reinforced those analyzed by the FDA: Results indicated a “deepening benefit beyond the 3-year treatment period” and reduced the risk of disease recurrence by 28.5% (HR, 0.715; 95% CI, 0.609-0.840). Trial participants will be monitored for long-term outcomes, including overall survival.
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“The FDA approval of Kisqali for this early breast cancer population, including those with [node-negative] disease, is a pivotal moment in improving our approach to care,” said Dennis J. Slamon, MD, director of clinical/translational research at UCLA Jonsson Comprehensive Care Center and Chairman of the Board of Transitional Research in Oncology (TRIO) and NATALEE 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.”
Breast cancer is the second most common cancer among US women.3 Among these women, 90% of cases are diagnosed in the early stages—stage 1 through stage 3—and are “treated promptly with curative intent.” Despite this, individuals with stage 2 and stage 3 HR+/HER2- early breast cancer are at risk of that cancer returning, frequently as incurable metastatic disease. Additionally, 10% of those diagnosed with high-risk node-negative early breast cancer may experience recurrence within the first 3 years following diagnosis.
For early breast cancer treatment, ribociclib should be taken orally, with or without food, once-daily at a dose of 400 mg (two 200 mg tablets) for 3 weeks on and 1 week off, in combination with 4 weeks of any aromatase inhibitor. Ribociclib therapy should continue for 3 years. At a 400 mg dose, data showed that the safety profile of the drug was well-tolerated; discontinuations were primarily driven by asymptomatic laboratory findings.
Adverse events in the ribociclib plus aromatase inhibitor group included neutropenia, liver-related adverse events, QT prolongation, and interstitial lung disease/pneumonitis.
Ribociclib is a selective cyclin-dependent kinase inhibitor. This class of drugs slows cancer progression through the inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6). The drug has also been approved to treat adults with HR+/HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as an initial endocrine therapy or following disease progression on endocrine therapy in men or postmenopausal women.
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References
FDA approves Novartis Kisqali to reduce risk of recurrence in people with HR+/HER2- early breast cancer. News release. Novartis. September 17, 2024. Accessed September 18, 2024. https://www.prnewswire.com/news-releases/fda-approves-novartis-kisqali-to-reduce-risk-of-recurrence-in-people-with-hrher2--early-breast-cancer-302250689.html
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
Breast cancer in young women. CDC. Reviewed September 3, 2024. Accessed September 18, 2024. https://www.cdc.gov/bring-your-brave/breast-cancer-in-young-women
