Overall survival of CDK4/6-inhibitors-based treatments in clinically relevant subgroups of metastatic breast cancer: systematic review and meta-analysis

Daniele Generali, Sergio Venturini, Ida Paris

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors þ endocrine therapy (ET) prolonged progression-free survival as first- or second-line therapy for hormone receptor-positive (HRþ)/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 þ ET reporting OS data in first- or second-line therapy of HRþ/HER2-negative pre- or postmenopausal metastatic breast cancer. A random effect model was applied for the analyses. Heterogeneity was assessed with I2statistic. 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] 1⁄4 0.68, 95% confidence interval [CI] 1⁄4 0.54 to 0.85, I2 1⁄4 0.0%) and with visceral involvement (HR 1⁄4 0.76, 95% CI 1⁄4 0.65 to 0.89, I2 1⁄4 0.0%), with at least 3 metastatic sites (HR 1⁄4 0.75, 95% CI 1⁄4 0.60 to 0.94, I2 1⁄4 11.6%), in an endocrine-resistant (HR 1⁄4 0.79, 95% CI 1⁄4 0.67 to 0.93, I2 1⁄4 0.0%) and sensitive subset (HR 1⁄4 0.73, 95% CI 1⁄4 0.61 to 0.88, I2 1⁄4 0.0%), for younger than 65 years (HR 1⁄4 0.80, 95% CI 1⁄4 0.67 to 0.95, I2 1⁄4 0.0%) and 65 years or older (HR 1⁄4 0.71, 95% CI 1⁄4 0.53 to 0.95, I2 1⁄4 44.4%), in postmenopausal (HR 1⁄4 0.76, 95% CI 1⁄4 0.67 to 0.86, I2 1⁄4 0.0%) and pre- or perimenopausal setting (HR 1⁄4 0.76, 95% CI 1⁄4 0.60 to 0.96, I2 1⁄4 0.0%) as well as in chemotherapy-naive patients (HR 1⁄4 0.72, 95% CI 1⁄4 0.55 to 0.93, I2 1⁄4 0.0%). Conclusions: CDK4/6-inhibitors þ 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.
Lingua originaleEnglish
pagine (da-a)1-7
Numero di pagine7
RivistaJournal of the National Cancer Institute
DOI
Stato di pubblicazionePubblicato - 2020

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