Overall Survival of CDK4/6-Inhibitor–Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis. (14th May 2020)

• Record Type: Journal Article
• Authors: 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; Di Leo, Angelo; Generali, Daniele
• Is Part Of: Journal of the National Cancer Institute. Volume 112:Number 11(2020)
• Page Start: 1089
• Page End: 1097
• Publication Date: 2020-05-14
• Subjects: Cancer -- Periodicals; Cancer -- Research -- Periodicals; 616.994
• DOI: 10.1093/jnci/djaa071
• Languages: English
• ISSNs: 0027-8874

Abstract

Abstract: Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors + endocrine therapy (ET) prolonged progression-free survival as first- or second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer prognosis. Given the recent publication of overall survival (OS) data for the 3 CDK4/6-inhibitors, 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 or III randomized clinical trials of CDK4/6-inhibitors + ET reporting OS data in first- or second-line therapy of HR+/HER2-negative pre- or postmenopausal metastatic breast cancer. A random effect model was applied for the analyses. Heterogeneity was assessed with I 2 statistic. Subgroup analysis was 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 (3421 patients). A clear OS benefit was observed in patients without (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.54 to 0.85, I 2 = 0.0%) and with visceral involvement (HR = 0.76, 95% CI = 0.65 to 0.89, I 2 = 0.0%), with at least 3 metastatic sites (HR = 0.75, 95% CI = 0.60 to 0.94, I 2 = 11.6%), in an endocrine-resistant (HR = 0.79, 95% CI = 0.67 to 0.93, I 2 = 0.0%) and sensitive subset (HR = 0.73, 95% CI = 0.61 to 0.88, I 2 = 0.0%), for younger than 65 years (HR = 0.80, 95% CI = 0.67 to 0.95, I 2 = 0.0%) and 65 years or older (HR = 0.71, 95% CI = 0.53 to 0.95, I 2 = 44.4%), in postmenopausal (HR = 0.76, 95% CI = 0.67 to 0.86, I 2 = 0.0%) and pre- or perimenopausal setting (HR = 0.76, 95% CI = 0.60 to 0.96, I 2 = 0.0%) as well as in chemotherapy-naïve patients (HR = 0.72, 95% CI = 0.55 to 0.93, I 2 = 0.0%). Conclusions: CDK4/6-inhibitors + ET combinations compared with 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.