The approval is based on results from the Phase III NATALEE trial, which showed a significant and clinically relevant 25.1% reduction in the risk of disease recurrence in a broad population of patients with HR+/HER2- stage II and III early breast cancer treated with Kisqali in combination with endocrine therapy (ET) compared to ET alone, including those with non-high-risk disease. The invasive disease-free survival (iDFS) benefit was consistently observed across all patient subgroups.
“The FDA approval of Kisqali for this early breast cancer patient population, including those with N0 disease, marks a pivotal moment in advancing our approach to treatment,” said Dennis J. Slamon, MD, Director of Clinical/Translational Research at the UCLA Jonsson Cancer Center and Chair of the Translational Research in Oncology (TRIO) Board, and principal investigator of the NATALEE trial. “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, when combined with endocrine therapy, may help further reduce the risk of cancer recurrence.”
For early breast cancer (EBC), Kisqali is taken with or without food, at a daily oral dose of 400 mg (two 200 mg tablets) for three weeks, followed by a one-week break, in combination with an aromatase inhibitor (AI) for four weeks. Patients should take Kisqali for a period of three years.
The NATALEE trial showed that the safety profile of Kisqali at the 400 mg dose was well tolerated, with treatment discontinuations primarily due to asymptomatic laboratory findings. Adverse events (AEs) of special interest in the Kisqali + ET arm included: neutropenia (62.5%, 44.3%), hepatic events (26.4%, 8.6%), QT prolongation (5.3%, 1.0%), and interstitial lung disease/pneumonitis (1.5%, 0.0%).
An updated analysis of the NATALEE trial, recently presented at the European Society for Medical Oncology (ESMO) Congress 2024, reinforces the data analyzed by the FDA. The results showed continued benefit beyond the three-year treatment period, reducing the risk of recurrence by 28.5% compared to endocrine therapy alone, in patients with HR+/HER2- stage II and III early breast cancer. Novartis will continue to evaluate patients in the NATALEE trial for long-term outcomes, including overall survival.
Approximately 90% of breast cancer cases in the U.S. are diagnosed at early stages (stages I-III) and treated promptly with curative intent, often with adjuvant endocrine therapy. Despite this, people with HR+/HER2- stage II and III early breast cancer remain at risk for recurrence, often as incurable metastatic disease.
Recurrence remains a lifelong concern, although most tumors recur within the first few years, even in those cases without lymph node involvement. Despite endocrine therapy, 10% of people with high-risk N0 disease may face recurrences within the first three years after diagnosis.
“With this approval, we are redefining treatment options for a broader population of people affected by breast cancer who face persistent risk of recurrence,” said Victor Bultó, President, Novartis, U.S. “We continue to transform cancer care with Kisqali, expanding its established profile in the metastatic setting and now helping more people remain cancer-free after an early-stage diagnosis.”
“Breast cancer treatment can take a toll on both physical and mental health, and it’s common to worry about the risk of recurrence. This risk varies for each person, depending on many factors, but it should not be underestimated,” said Valarie Worthy, co-founder and vice president of Community Outreach and Engagement at Touch, The Black Breast Cancer Alliance. “The FDA approval of Kisqali for more people with breast cancer is welcome news and offers a new option to help manage and reduce the risk of cancer coming back.”
Kisqali has been approved as a treatment for patients with metastatic breast cancer (MBC) in 99 countries around the world, including approval by the US FDA and the European Commission. In the US, Kisqali is indicated for the treatment of adults with HR+/HER2- advanced or metastatic breast cancer, in combination with an aromatase inhibitor (AI) as initial endocrine therapy, or with fulvestrant as initial therapy or following disease progression in postmenopausal women or men.
In the European Union, Kisqali is approved for the treatment of women with HR+/HER2- advanced or metastatic breast cancer, in combination with an AI or fulvestrant as initial endocrine therapy or after disease progression. In pre- or perimenopausal women, endocrine therapy should be combined with a gonadotropin-releasing hormone agonist.
