Article (Scientific journals)
Overall survival of CDK4/6-inhibitors-based treatments in clinically relevant subgroups of metastatic breast cancer: systematic review and meta-analysis.
Schettini, Francesco; Giudici, Fabiola; Giuliano, Mario et al.
2020In Journal of the National Cancer Institute
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Keywords :
CDK4/6-inhibitors; hormone receptors; hormone therapy; metastatic breast cancer; overall survival; subgroup analysis; oncology
Abstract :
[en] BACKGROUND: CDK4/6-inhibitors (CDK4/6i)+endocrine therapy (ET) prolonged progression-free survival as first/second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) prognosis. Given the recent publication of overall survival (OS) data for the three CDK4/6i, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups. METHODS: We conducted a systematic literature search to select all available phase II/III randomized clinical trials of CDK4/6i+ET reporting OS data in first/second-line therapy of HR+/HER2-negative pre/postmenopausal MBC. A random effect model was applied for the analyses. Heterogeneity was assessed with I2 statistic. Subgroup analysis were performed to explore the effect of study-level factors. The project was registered in the Open Science Framework database (doi: 10.17605/OSF.IO/TNZQP). RESULTS: Six studies were included in our analyses (3,421 patients). A clear OS benefit was observed in patients without (HR:0.68, 95%CI:0.54-0.85, I2=0.0%) and with visceral involvement (HR:0.76, 95%CI:0.65-0.89, I2=0.0%), with ≥3 metastatic sites (HR:0.75, 95%CI:0.60-0.94, I2=11.6%), in endocrine resistant (HR:0.79, 95%CI:0.67-0.93, I2=14.4%). and sensitive subset (HR:0.73, 95%CI:0.61-0.88, I2=0.0%), for age <65 (HR:0.80, 95%CI:0.67-0.95, I2=0.0%) and ≥65 years (HR:0.71, 95%CI:0.53-0.95, I2=44.4%), in postmenopausal (HR:0.75, 95%CI:0.66-0.86, I2=0.0%) and pre/perimenopausal setting (HR:0.76, 95%CI:0.60-0.96, I2=0.0%), as well as in CT-naïve patients (HR:0.72, 95%CI:0.55-0.93, I2=0.0%). CONCLUSIONS: CDK4/6i+ET combinations compared to ET alone improve OS independent of age, menopausal status, endocrine sensitiveness and visceral involvement, and should be preferred as upfront therapy instead of endocrine monotherapy.
Disciplines :
Author, co-author :
Schettini, Francesco
Giudici, Fabiola
Giuliano, Mario
Cristofanilli, Massimo
Arpino, Grazia
Del Mastro, Lucia
Puglisi, Fabio
De Placido, Sabino
Paris, Ida
De Placido, Pietro
Venturini, Sergio
De Laurentis, Michelino
Conte, Pierfranco
Juric, Dejan
Llombart-Cussac, Antonio
Pusztai, Lajos
Prat, Aleix
Jerusalem, Guy  ;  Université de Liège - ULiège > Département des sciences cliniques > Oncologie
Di Leo, Angelo
Generali, Daniele
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Language :
Title :
Overall survival of CDK4/6-inhibitors-based treatments in clinically relevant subgroups of metastatic breast cancer: systematic review and meta-analysis.
Publication date :
May 2020
Journal title :
Journal of the National Cancer Institute
Publisher :
Oxford University Press, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email:
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since 10 November 2020


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