Overall survival of CDK4/6-inhibitors-based treatments in clinically relevant subgroups of metastatic breast cancer: systematic review and meta-analysis
A partir d’une revue systématique de la littérature (6 études, 3 421 patientes), cette méta-analyse évalue l’efficacité, du point de vue de la survie globale, des inhibiteurs anti-CDK4/6 chez des patientes atteintes d’un cancer du sein de stade métastatique, selon certaines spécificités (sous-type moléculaire de la tumeur, statut ménopausique, nombre de lignes de traitements, etc.)
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.