- MeSH
- časná detekce nádoru MeSH
- chování snižující riziko MeSH
- dědičné nádorové syndromy * MeSH
- genetická predispozice k nemoci MeSH
- lidé MeSH
- nádory prsu * diagnóza genetika prevence a kontrola MeSH
- nádory vaječníků * diagnóza epidemiologie genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- směrnice pro lékařskou praxi MeSH
- MeSH
- kryoprezervace MeSH
- lidé MeSH
- nádory * terapie MeSH
- těhotenství MeSH
- zachování plodnosti * MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
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 (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2.5 mg/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. Clinical trials number: NCT01958021.
- MeSH
- aminopyridiny aplikace a dávkování MeSH
- dvojitá slepá metoda MeSH
- letrozol aplikace a dávkování MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie metabolismus patologie MeSH
- lymfatické metastázy MeSH
- míra přežití MeSH
- nádorové biomarkery metabolismus MeSH
- nádory jater farmakoterapie metabolismus sekundární MeSH
- nádory plic farmakoterapie metabolismus sekundární MeSH
- nádory prsu farmakoterapie metabolismus patologie MeSH
- následné studie MeSH
- prognóza MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- puriny aplikace a dávkování MeSH
- receptor erbB-2 metabolismus MeSH
- receptory pro estrogeny metabolismus MeSH
- receptory progesteronu metabolismus MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
