Ribociclib (Kisqali) demonstrated a 26% risk reduction in distant disease-free survival and a 28% risk reduction in recurrence-free survival in patients with HR+/HER2- early breast cancer.
Ribociclib (Kisqali; Novartis) plus endocrine therapy lowered the risk of cancer recurrence by 25.2% in individuals with stage II and III hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer compared to endocrine therapy alone, according to the results of a phase 3 trial presented at the 2023 American Society of Clinical Oncology Annual Meeting.
Additionally, the results demonstrated a consistent and clinically meaningful invasive disease-free survival (iDFS) benefit across key pre-specified subgroups, according to the phase 3 NATALEE trial (NCT03701334).
“Patients diagnosed with HR+/HER2- early breast cancer remain at risk of cancer recurrence, given that one-third of patients diagnosed with stage II and more than half of those diagnosed with stage III will unfortunately experience a return of their cancer,” Shreeram Aradhye, MD, president of Global Drug Development and chief medical officer at Novartis, said in a statement. “The compelling data from NATALEE highlight the potential of [ribociclib] to reduce the risk of cancer recurrence in this at-risk population, including node-negative patients, while maintaining a favorable safety profile. These potentially practice-changing results reinforce the unique and well-established profile of [ribociclib] as a proven treatment in HR+/HER2- metastatic breast cancer.”
The NATALEE phase 3 open-label, randomized trial evaluated the efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment compared to endocrine therapy alone. The trial enrolled 5101 individuals with HR+/HER2- early breast cancer across 20 countries.
The median duration of follow up was 34 months, ranging from 21 to 48 months, with clinical benefits observed after approximately 2 years.
Data for ribociclib across all secondary endpoints were also consistent, which included a 26% risk reduction in distant disease-free survival and a 28% risk reduction in recurrence-free survival. Investigators also observed a trend for improvement in overall survival.
Additionally, the results showed a consistent clinically meaningful iDFS across key pre-specified subgroups, including AJCC Tumor Stage II, AJCC Tumor stage III, node-negative disease, node-positive disease, pre-menopausal women and men, and post-menopausal women.
Ribociclib in the 400 mg strength had a favorable safety profile with low rates of symptomatic adverse events (AEs). Investigators found that there was a limited need for dose modification when the drug was administered for up to 3 years.
The most frequent AEs of special interest, defined as grade 3 or higher, were neutropenia at 43.8% and liver-related AEs, such as elevated transaminases, at 8.3%.
Furthermore, rates of grade 3 or higher QT interval prolongation and diarrhea were low, at 1% and 0.6%, respectively.
“These landmark results will fundamentally change how we treat patients with stage II and III HR+/HER2- early breast cancer who are in need of new, well-tolerated options that prevent their cancer from coming back,” Dennis J. Slamon, MD, director of Clinical/Translational Research at the University of California Los Angeles’s Jonsson Comprehensive Cancer Center and chairman and executive director of Translational Research In Oncology, said in the statement. “Addressing this unmet need across such a broad patient population could help streamline treatment decisions for health care providers and keep many more at-risk patients cancer-free without disrupting their daily lives.”
Novartis plans to submit the data from the phase 3 trial to regulatory authorities in the United States and Europe before the end of 2023.
Novartis Kisqali significantly reduced the risk of recurrence by 25% across a broad population of patients with early breast cancer; clinically meaningful benefit was consistent across subgroups. News release. Novartis. June 2, 2023. Accessed June 2, 2o23. https://www.novartis.com/news/media-releases/novartis-kisqali-significantly-reduced-risk-recurrence-25-across-broad-population-patients-early-breast-cancer-clinically-meaningful-benefit-was-consistent-across-subgroups