Novartis announced positive topline results from an interim analysis of NATALEE, a Phase III trial evaluating ribociclib plus endocrine therapy in a broad population of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2) early breast cancer at risk of recurrence.
The Independent Data Monitoring Committee recommended stopping the trial early as the primary endpoint of invasive disease-free survival has been met as ribociclib plus ET significantly reduced the risk of disease recurrence, compared to standard adjuvant ET alone, with consistent benefit in patients with stage II and stage III EBC regardless of nodal involvement.
“While most patients are diagnosed and treated early with the aim to cure breast cancer, the risk of cancer returning, often as metastatic disease, peaks within three years after diagnosis, but never goes away completely,” said Dennis J. Slamon, MD, director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center and Chairman and Executive Director of Translational Research In Oncology and NATALEE trial lead investigator.
“There is a critical need for new, well-tolerated options that keep patients cancer-free without disrupting quality of life. The NATALEE trial, where ribociclib was given for three years plus ET, was designed with these unmet needs in mind, and it is extremely encouraging that this study met its primary endpoint,” he added.
Per the NATALEE study protocol, patient follow-up will continue to evaluate long-term outcomes, including overall survival.
“The positive topline results from NATALEE represent a major milestone in our ambition to expand the benefits of ribociclib to patients with earlier stages of breast cancer, building on the heritage of this effective treatment in HR+/HER2- metastatic breast cancer,” said Shreeram Aradhye, M.D., president of Global Drug Development and chief medical officer of Novartis.
“These data have the potential to be paradigm-shifting for patients at risk of recurrence, including those with no nodal involvement, who have limited well-tolerated options to prevent recurrence. Our teams are working on submissions to health authorities around the world with the hope to bring ribociclib to many more patients diagnosed with breast cancer.”
“The result of the NATALEE trial is a welcome development in the management of breast cancer, offering new hope for a longer life in a broad population of patients with stage II and III HR-positive/HER2-negative early breast cancer at risk of recurrence,” said Dr. Rosario V. Pitargue, the president of Philippine Society of Medical Oncology.
“These findings build on the legacy of ribociclib in metastatic breast cancer (MBC). Ribociclib is the first and only CDK4/6 inhibitor so far to have shown both consistent and significant improvements in overall survival across 3 phase III trials,” said Novartis Healthcare Philippines country president Joel Chong.
NATALEE is a global Phase III multi-center, randomized, open-label trial to evaluate the efficacy and safety of ribociclib with ET as adjuvant treatment versus ET alone in patients with HR+/HER2- EBC, being conducted in collaboration with Translational Research In Oncology.
The primary endpoint of NATALEE is iDFS as defined by the Standardized Definitions for Efficacy End Points criteria; secondary endpoints include safety, quality of life, and overall survival, among others. iDFS is a composite endpoint in EBC adjuvant trials, which incorporates locoregional relapse, ipsilateral and contralateral invasive breast cancer, distant recurrence, and types of new cancer events or death from any cause.
Approximately 5,100 adult patients with HR+/HER2- EBC across 20 countries were randomized in the trial, including patients with tumor stages IIA (select patients), IIB or III, regardless of nodal involvement. NATALEE explored a lower starting dose (400 mg) of ribociclib than the dose approved for treatment in MBC (600 mg) with the goal to minimize disruptions to patient quality of life without compromising efficacy.
Ribociclib, on the other hand, has consistently demonstrated overall survival benefit while preserving or improving quality of life across three Phase III trials. Updates to the NCCN Guidelines® for breast cancer, released in January 2023, recommend ribociclib as the only Category 1 preferred CDK4/6 inhibitor for first-line treatment of patients with HR+/HER2- MBC when combined with an AI.
Additionally, ribociclib has the highest rating of any CDK4/6 inhibitor on the ESMO Magnitude of Clinical Benefit Scale, achieving a score of five out of five for first-line premenopausal patients with HR+/HER2- advanced breast cancer.
Ribociclib, in combination with either letrozole or fulvestrant has uniquely, among other CDK4/6 inhibitors, received a score of four out of five for postmenopausal patients with HR+/HER2- advanced breast cancer treated in the first line.