Overall survival with ribociclib plus endocrine therapy in breast cancer
Journal
New England Journal of Medicine
Journal Volume
381
Journal Issue
4
Pages
307-316
Date Issued
2019
Author(s)
Im S.-A
Bardia A
Harbeck N
Colleoni M
Franke F
Chow L
Sohn J
Lee K.-S
Campos-Gomez S
Villanueva-Vazquez R
Jung K.-H
Chakravartty A
Hughes G
Gounaris I
Rodriguez-Lorenc K
Taran T
Hurvitz S
Tripathy D.
Abstract
BACKGROUND: An earlier analysis of this phase 3 trial showed that the addition of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided a greater benefit with regard to progression-free survival than endocrine therapy alone in premenopausal or perimenopausal patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report the results of a protocol-specified interim analysis of the key secondary end point of overall survival. METHODS: We randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen). Overall survival was evaluated with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods. RESULTS: A total of 672 patients were included in the intention-to-treat population. There were 83 deaths among 335 patients (24.8%) in the ribociclib group and 109 deaths among 337 patients (32.3%) in the placebo group. The addition of ribociclib to endocrine therapy resulted in significantly longer overall survival than endocrine therapy alone. The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5 to 76.0) in the ribociclib group and 46.0% (95% CI, 32.0 to 58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test). The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the overall intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50 to 0.98). The percentage of patients who received subsequent antineoplastic therapy was balanced between the groups (68.9% in the ribociclib group and 73.2% in the placebo group). The time from randomization to disease progression during receipt of second-line therapy or to death was also longer in the ribociclib group than in the placebo group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.55 to 0.87). CONCLUSIONS: This trial showed significantly longer overall survival with a CDK4/6 inhibitor plus endocrine therapy than with endocrine therapy alone among patients with advanced hormone-receptor-positive, HER2-negative breast cancer. No new concerns regarding toxic effects emerged with longer follow-up. Copyright ? 2019 Massachusetts Medical Society.
SDGs
Other Subjects
anastrozole; aromatase inhibitor; goserelin; hormone receptor; letrozole; placebo; ribociclib; tamoxifen; aminopyridine derivative; antineoplastic agent; aromatase inhibitor; cyclin dependent kinase; epidermal growth factor receptor 2; ERBB2 protein, human; estrogen receptor; progesterone receptor; protein kinase inhibitor; purine derivative; ribociclib; tamoxifen; adult; antineoplastic activity; Article; breast cancer; cancer hormone therapy; cancer recurrence; cancer survival; comparative effectiveness; controlled study; disease exacerbation; double blind procedure; female; follow up; hepatobiliary disease; human; human epidermal growth factor receptor 2 negative breast cancer; major clinical study; metastasis; multiple cycle treatment; neutropenia; overall survival; phase 3 clinical trial; premenopause; priority journal; progression free survival; QT prolongation; randomized controlled trial; antagonists and inhibitors; breast tumor; climacterium; clinical trial; comparative study; intention to treat analysis; middle aged; mortality; survival analysis; Adult; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Cyclin-Dependent Kinases; Double-Blind Method; Female; Follow-Up Studies; Humans; Intention to Treat Analysis; Middle Aged; Perimenopause; Premenopause; Protein Kinase Inhibitors; Purines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Survival Analysis; Tamoxifen
Publisher
Massachussetts Medical Society
Type
journal article