Results from the phase III NATALEE trial presented at the 2023 San Antonio Breast Cancer Symposium show significant invasive disease–free survival benefits with ribociclib plus hormone therapy in patients with early-stage hormone receptor–positive, HER2-negative breast cancer at risk of disease recurrence.

The NATALEE trial enrolled 5101 patients with stage IIA, IIB, or III hormone receptor–positive, HER2-negative breast cancer at risk for recurrence, randomly assigned to receive either adjuvant ribociclib for 3 years with hormonal therapy for at least 5 years or hormonal therapy alone for at least 5 years. The dose used was 400 milligrams per day, lower than the dose used for metastatic breast cancer to enhance tolerability and compliance and to induce a greater suppression of proliferation by extending the duration of treatment with CDK4/6 inhibitor. Results showed consistent benefits across patient subgroups, including those with node-negative, stage II, and stage III disease, and pre- and postmenopausal women: combination regimen led to a significantly extended invasive disease–free survival compared to hormone therapy alone: invasive disease–free survival rates at 3 years were 90.7% with the combination and 87.6% with only hormone therapy, which represents approximately a 25% reduction in the risk of recurrence. Analyses of secondary endpoints of distant disease–free survival and recurrence-free survival supported ribociclib with hormone therapy, with no new safety signals; overall survival data are still incomplete. During data discussion it was pointed out that given the high costs of therapy there’s a compelling need to take into account economic sustainability issues (patients needed to treat for a benefit in invasive disease-free survival is above 50). «Researchers are intensifying efforts to identify biomarkers for the selection of subgroups of patients who could benefit the most, even if it is not easy to identify such markers», lead author Gabriel Hortobagyi from MD Anderson Cancer Center concluded.