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Your search keyword '"Sonke, G S"' showing total 6 results
Start Over Author "Sonke, G S" Topic ribociclib
6 results on '"Sonke, G S"'

3. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer.

Author

Hortobagyi, G N, Stemmer, S M, Burris, H A, Yap, Y S, Sonke, G S, Paluch-Shimon, S, Campone, M, Petrakova, K, Blackwell, K L, and Winer, E P

Subjects
*LETROZOLE, *HORMONE receptor positive breast cancer, *HER2 gene, *EPIDERMAL growth factor receptors, *THERAPEUTICS
Abstract

Background: The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here, we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study. Patients and methods: A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1 : 1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2.5mg/day; continuous) or placebo plus letrozole. The primary end point was locally assessed PFS. The key secondary end point was overall survival (OS). Other secondary end points included overall response rate (ORR) and safety. Biomarker analysis was an exploratory end point. Results: At the time of the second interim analysis, the median duration of follow-up was 26.4 months. Median PFS was 25.3 months [95% confidence interval (CI) 23.0-30.3] for ribociclib plus letrozole and 16.0 months (95% CI 13.4-18.2) for placebo plus letrozole (hazard ratio 0.568; 95% CI 0.457-0.704; log-rank P=9.63×10-8). Ribociclib treatment benefit was maintained irrespective of PIK3CA or TP53 mutation status, total Rb, Ki67, or p16 protein expression, and CDKN2A, CCND1, or ESR1 mRNA levels. Ribociclib benefit was more pronounced in patients with wild-type versus altered receptor tyrosine kinase genes. OS data remain immature, with 116 deaths observed; 50 in the ribociclib arm and 66 in the placebo arm (hazard ratio 0.746; 95% CI 0.517-1.078). The ORR was 42.5% versus 28.7% for all patients treated with ribociclib plus letrozole versus placebo plus letrozole, respectively, and 54.5% versus 38.8%, respectively, for patients with measurable disease. Safety results, after a further 11.1 months of follow-up, were comparable with those reported at the first analysis, with no new or unexpected toxicities observed, and no evidence of cumulative toxicity. Conclusions: The improved efficacy outcomes and manageable tolerability observed with first-line ribociclib plus letrozole are maintained with longer follow-up, relative to letrozole monotherapy. [ABSTRACT FROM AUTHOR]

Published
2018
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4. Overall survival with ribociclib plus fulvestrant in advanced breast cancer

Author

Giulia Val Bianchi, Xavier Pivot, Guy Jerusalem, Luis de la Cruz-Merino, Stephen Chia, Tetiana Taran, Gabe S. Sonke, Seock-Ah Im, Arnd Nusch, Francisco J. Esteva, Patrick Neven, J. Thaddeus Beck, Michelino De Laurentiis, Miguel Martin, Arunava Chakravartty, Dennis J. Slamon, K. Petrakova, Yingbo Wang, Karen Rodriguez-Lorenc, Manu Sondhi, Peter A. Fasching, Slamon, D. J., Neven, P., Chia, S., Fasching, P. A., De Laurentiis, M., Im, S. -A., Petrakova, K., Bianchi, G. V., Esteva, F. J., Martin, M., Nusch, A., Sonke, G. S., De La Cruz-Merino, L., Beck, J. T., Pivot, X., Sondhi, M., Wang, Y., Chakravartty, A., Rodriguez-Lorenc, K., Taran, T., and Jerusalem, G.

Subjects
Oncology, medicine.medical_specialty, medicine.drug_class, Receptor, ErbB-2, Aminopyridines, Ribociclib, Breast Neoplasms, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Drug Administration Schedule, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Overall survival, Humans, 030212 general & internal medicine, Progression-free survival, Fulvestrant, Purine, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, Cancer, General Medicine, Middle Aged, medicine.disease, Progression-Free Survival, Clinical trial, Postmenopause, Aminopyridine, Receptors, Estrogen, Estrogen, Purines, Female, business, Receptors, Progesterone, Breast Neoplasm, medicine.drug, Human
Abstract

In 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.).

Published
2020

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