Slamon, Dennis JNeven, PatrickChia, StephenFasching, Peter ADe Laurentiis, MichelinoIm, Seock-AhPetrakova, KatarinaBianchi, Giulia VEsteva, Francisco JMartín, MiguelNusch, ArndSonke, Gabe SDe la Cruz-Merino, LuisBeck, J ThaddeusPivot, XavierSondhi, ManuWang, YingboChakravartty, ArunavaRodriguez-Lorenc, KarenTaran, TetianaJerusalem, Guy2023-02-082023-02-082019-12-11http://hdl.handle.net/10668/14815In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Here we report the results of a protocol-specified second interim analysis of overall survival. Patients were randomly assigned in a 2:1 ratio to receive either ribociclib or placebo in addition to fulvestrant as first-line or second-line treatment. Survival was evaluated by means of a stratified log-rank test and summarized with the use of Kaplan-Meier methods. This analysis was based on 275 deaths: 167 among 484 patients (34.5%) receiving ribociclib and 108 among 242 (44.6%) receiving placebo. Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant. The estimated overall survival at 42 months was 57.8% (95% confidence interval [CI], 52.0 to 63.2) in the ribociclib group and 45.9% (95% CI, 36.9 to 54.5) in the placebo group, for a 28% difference in the relative risk of death (hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.00455). The benefit was consistent across most subgroups. In a descriptive update, median progression-free survival among patients receiving first-line treatment was 33.6 months (95% CI, 27.1 to 41.3) in the ribociclib group and 19.2 months (95% CI, 14.9 to 23.6) in the placebo group. No new safety signals were observed. Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant in patients with hormone-receptor-positive, HER2-negative advanced breast cancer. (Funded by Novartis; MONALEESA-3 ClinicalTrials.gov number, NCT02422615.).enAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDrug Administration ScheduleFemaleFulvestrantHumansKaplan-Meier EstimateMiddle AgedPostmenopauseProgression-Free SurvivalPurinesReceptor, ErbB-2Receptors, EstrogenReceptors, Progesteroneresearch article31826360open access10.1056/NEJMoa19111491533-4406https://doi.org/10.1056/nejmoa1911149